Messages between computer users via COMPUTER COMMUNICATION NETWORKS. This feature duplicates most of the features of paper mail, such as forwarding, multiple copies, and attachments of images and other file types, but with a speed advantage. The term also refers to an individual message sent in this way.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Mechanical food dispensing machines.
The study of the origin, nature, properties, and actions of drugs and their effects on living organisms.
The branch of pharmacology that deals directly with the effectiveness and safety of drugs in humans.
A receptor that is specific for IGF-II and mannose-6-phosphate. The receptor is a 250-kDa single chain polypeptide which is unrelated in structure to the type 1 IGF receptor (RECEPTOR, IGF TYPE 1) and does not have a tyrosine kinase domain.
Phosphoric acid esters of mannose.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
The variable phenotypic expression of a GENE depending on whether it is of paternal or maternal origin, which is a function of the DNA METHYLATION pattern. Imprinted regions are observed to be more methylated and less transcriptionally active. (Segen, Dictionary of Modern Medicine, 1992)
A well-characterized neutral peptide believed to be secreted by the LIVER and to circulate in the BLOOD. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults.
A protein-tyrosine kinase receptor that is closely related in structure to the INSULIN RECEPTOR. Although commonly referred to as the IGF-I receptor, it binds both IGF-I and IGF-II with high affinity. It is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The beta subunit contains an intrinsic tyrosine kinase domain.
A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.
A vocabulary database of universal identifiers for laboratory and clinical test results. Its purpose is to facilitate the exchange and pooling of results for clinical care, outcomes management, and research. It is produced by the Regenstrief Institute. (LOINC and RELMA [Internet]. Indianapolis: The Regenstrief Institute; c1995-2001 [cited 2002 Apr 2]. Available from
Tumors or cancer of the LUNG.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.
The infiltrating of tissue specimens with paraffin, as a supporting substance, to prepare for sectioning with a microtome.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Those characteristics that distinguish one SEX from the other. The primary sex characteristics are the OVARIES and TESTES and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction.
A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.
The internal individual struggle resulting from incompatible or opposing needs, drives, or external and internal demands. In group interactions, competitive or opposing action of incompatibles: antagonistic state or action (as of divergent ideas, interests, or persons). (from Merriam-Webster's Collegiate Dictionary, 10th ed)
PASSERIFORMES of the suborder, Oscines, in which the flexor tendons of the toes are separate, and the lower syrinx has 4 to 9 pairs of tensor muscles inserted at both ends of the tracheal half rings. They include many commonly recognized birds such as CROWS; FINCHES; robins; SPARROWS; and SWALLOWS.
The total process by which organisms produce offspring. (Stedman, 25th ed)
The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics.
The normal length of time of an organism's life.
Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.
The surgical removal of one or both ovaries.
A cell line derived from cultured tumor cells.
Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Tumors or cancer of the human BREAST.
Interruption of sympathetic pathways, by local injection of an anesthetic agent, at any of four levels: peripheral nerve block, sympathetic ganglion block, extradural block, and subarachnoid block.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.
A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.
A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS.
A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.
Substances which lower blood glucose levels.
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation.
A subset of ubiquitin protein ligases that are formed by the association of a SKP DOMAIN PROTEIN, a CULLIN DOMAIN PROTEIN and a F-BOX DOMAIN PROTEIN.
A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.
The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.
An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.
A decapeptide that is cleaved from precursor angiotensinogen by RENIN. Angiotensin I has limited biological activity. It is converted to angiotensin II, a potent vasoconstrictor, after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME.
Technique for limiting use, activity, or movement by immobilizing or restraining animal by suspending from hindlimbs or tails. This immobilization is used to simulate some effects of reduced gravity and study weightlessness physiology.
A class of lipoproteins of very light (0.93-1.006 g/ml) large size (30-80 nm) particles with a core composed mainly of TRIGLYCERIDES and a surface monolayer of PHOSPHOLIPIDS and CHOLESTEROL into which are imbedded the apolipoproteins B, E, and C. VLDL facilitates the transport of endogenously made triglycerides to extrahepatic tissues. As triglycerides and Apo C are removed, VLDL is converted to INTERMEDIATE-DENSITY LIPOPROTEINS, then to LOW-DENSITY LIPOPROTEINS from which cholesterol is delivered to the extrahepatic tissues.
Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.
Cholesterol which is contained in or bound to high-density lipoproteins (HDL), including CHOLESTEROL ESTERS and free cholesterol.

In-vitro fertilization and culture of mouse embryos in vitro significantly retards the onset of insulin-like growth factor-II expression from the zygotic genome. (1/794)

In this study, the effect of in-vitro fertilization (IVF) and culture of mouse embryos in vitro on the normal expression of insulin-like growth factor-II (IFG-II) ligand and receptor was examined. The expression of IGF-II increased in a linear fashion at least up to the 8-cell stage of development. IGF-II expression in embryos collected fresh from the reproductive tract was significantly (P < 0.001) greater than in embryos fertilized in the reproductive tract and cultured in vitro (in-situ fertilized: ISF), and its expression was further reduced (P < 0.001) in IVF embryos at all development stages tested. The expression of IGF-II was significantly (P < 0.001) lower when embryos were cultured individually in 100 microl drops compared with culture in groups of 10 in 10 microl drops of medium. The addition of platelet activating factor to culture medium partially overcame this density-dependent decline of expression. Culture of ISF and IVF zygotes also caused the onset of new IGF-II mRNA transcription from the zygotic genome to be significantly (P < 0.001) retarded, until at least the 8-cell stage of development. This effect was greater (P < 0.05) for IVF than for ISF embryos. Neither IVF nor culture had any obvious effect on IFG-II/mannose-6-phosphate receptor (IGF-IIr) mRNA expression.  (+info)

High-affinity binding of the AP-1 adaptor complex to trans-golgi network membranes devoid of mannose 6-phosphate receptors. (2/794)

The GTP-binding protein ADP-ribosylation factor (ARF) initiates clathrin-coat assembly at the trans-Goli network (TGN) by generating high-affinity membrane-binding sites for the AP-1 adaptor complex. Both transmembrane proteins, which are sorted into the assembling coated bud, and novel docking proteins have been suggested to be partners with GTP-bound ARF in generating the AP-1-docking sites. The best characterized, and probably the major transmembrane molecules sorted into the clathrin-coated vesicles that form on the TGN, are the mannose 6-phosphate receptors (MPRs). Here, we have examined the role of the MPRs in the AP-1 recruitment process by comparing fibroblasts derived from embryos of either normal or MPR-negative animals. Despite major alterations to the lysosome compartment in the MPR-deficient cells, the steady-state distribution of AP-1 at the TGN is comparable to that of normal cells. Golgi-enriched membranes prepared from the receptor-negative cells also display an apparently normal capacity to recruit AP-1 in vitro in the presence of ARF and either GTP or GTPgammaS. The AP-1 adaptor is recruited specifically onto the TGN and not onto the numerous abnormal membrane elements that accumulate within the MPR-negative fibroblasts. AP-1 bound to TGN membranes from either normal or MPR-negative fibroblasts is fully resistant to chemical extraction with 1 M Tris-HCl, pH 7, indicating that the adaptor binds to both membrane types with high affinity. The only difference we do note between the Golgi prepared from the MPR-deficient cells and the normal cells is that AP-1 recruited onto the receptor-lacking membranes in the presence of ARF1.GTP is consistently more resistant to extraction with Tris. Because sensitivity to Tris extraction correlates well with nucleotide hydrolysis, this finding might suggest a possible link between MPR sorting and ARF GAP regulation. We conclude that the MPRs are not essential determinants in the initial steps of AP-1 binding to the TGN but, instead, they may play a regulatory role in clathrin-coated vesicle formation by affecting ARF.GTP hydrolysis.  (+info)

The Niemann-Pick C1 protein resides in a vesicular compartment linked to retrograde transport of multiple lysosomal cargo. (3/794)

Niemann-Pick C disease (NP-C) is a neurovisceral lysosomal storage disorder. A variety of studies have highlighted defective sterol trafficking from lysosomes in NP-C cells. However, the heterogeneous nature of additional accumulating metabolites suggests that the cellular lesion may involve a more generalized block in retrograde lysosomal trafficking. Immunocytochemical studies in fibroblasts reveal that the NPC1 gene product resides in a novel set of lysosome-associated membrane protein-2 (LAMP2)(+)/mannose 6-phosphate receptor(-) vesicles that can be distinguished from cholesterol-enriched LAMP2(+) lysosomes. Drugs that block sterol transport out of lysosomes also redistribute NPC1 to cholesterol-laden lysosomes. Sterol relocation from lysosomes in cultured human fibroblasts can be blocked at 21 degrees C, consistent with vesicle-mediated transfer. These findings suggest that NPC1(+) vesicles may transiently interact with lysosomes to facilitate sterol relocation. Independent of defective sterol trafficking, NP-C fibroblasts are also deficient in vesicle-mediated clearance of endocytosed [14C]sucrose. Compartmental modeling of the observed [14C]sucrose clearance data targets the trafficking defect caused by mutations in NPC1 to an endocytic compartment proximal to lysosomes. Low density lipoprotein uptake by normal cells retards retrograde transport of [14C]sucrose through this same kinetic compartment, further suggesting that it may contain the sterol-sensing NPC1 protein. We conclude that a distinctive organelle containing NPC1 mediates retrograde lysosomal transport of endocytosed cargo that is not restricted to sterol.  (+info)

Alternative mechanisms for trafficking of lysosomal enzymes in mannose 6-phosphate receptor-deficient mice are cell type-specific. (4/794)

Viable mice nullizygous in genes encoding the 300 kDa and the 46 kDa mannose 6-phosphate receptors (MPR 300 and MPR 46) and the insulin like growth factor II (IGF II) were generated to study the trafficking of lysosomal enzymes in the absence of MPRs. The mice have an I-cell disease-like phenotype, with increase of lysosomal enzymes in serum and normal activities in tissues. Surprisingly, the ability of MPR-deficient cells to transport newly synthesized lysosomal enzymes to lysosomes and the underlying mechanisms were found to depend on the cell type. MPR-deficient thymocytes target newly synthesized cathepsin D to lysosomes via an intracellular route. In contrast, hepatocytes and fibroblasts secrete newly synthesized cathepsin D. In fibroblasts recapture of secreted lysosomal enzymes, including that of cathepsin D, is limited and results in lysosomal storage, both in vivo and in vitro, whereas recapture by hepatocytes is remarkably effective in vivo and can result in lysosomal enzyme levels even above normal.  (+info)

Microsatellite instability is uncommon in breast cancer. (5/794)

In some tumors, defects in mismatch repair enzymes lead to errors in the replication of simple nucleotide repeat segments. This condition is commonly known as microsatellite instability (MSI) because of the frequent mutations of microsatellite sequences. Although the MSI phenotype is well recognized in some colon, gastric, pancreatic, and endometrial cancers, reports of MSI in breast cancer are inconsistent. We report here our experience with >10,000 amplifications of simple nucleotide repeats in noncoding genomic regions using DNA from 267 cases of breast cancer, including cases that represent all major histological types of breast cancer. We rarely (10 reactions) found unexpected bands in amplifications of tumor DNA that were not present in amplifications of normal DNA. Moreover, repeats of these reactions did not confirm microsatellite instability in a single case. We also evaluated the simple nucleotide repeats in the transforming growth factor type II receptor, insulin-like growth factor type II receptor, BAX, and E2F-4 genes, which are frequently mutated in tumors with microsatellite instability. No mutations of these genes were found in any of the 30 breast cancer cell lines and 61 primary breast cancer samples examined. These results indicate that mismatch repair errors characteristic of the MSI phenotype are uncommon in human breast cancer.  (+info)

The insulin-like growth factor axis and prostate cancer: lessons from the transgenic adenocarcinoma of mouse prostate (TRAMP) model. (6/794)

We have characterized the temporal expression of the insulin-like growth factor (IGF) axis in the transgenic adenocarcinoma of mouse prostate (TRAMP) model as prostate cancer progression in this model closely mimics that observed in the human disease, and the model provides samples representing the earliest stages of prostate cancer that are clinically the most difficult to obtain. We report that prostate-specific IGF-I mRNA expression increased during prostate cancer progression in TRAMP mice and was elevated in the accompanying metastatic lesions, whereas prostatic IGF-I mRNA remained at nontransgenic levels in androgen-independent disease. Expression of IGF-II mRNA, however, was reduced in primary prostate cancer, metastatic lesions, and androgen-independent disease. Expression of type-1 IGF receptor (IGF1R) mRNA, encoding the cognate receptor for both IGF-I and IGF-II, as well as type-2 IGF receptor (IGF2R) mRNA was not found to be altered during primary prostate cancer progression in intact TRAMP mice but was dramatically reduced in metastatic lesions and in androgen-independent disease. Similar to reports from clinical disease, serum IGF-I levels were observed to increase precociously in TRAMP mice early in disease progression but remained at nontransgenic levels after castration. Elevated serum levels of IGF-binding protein 2 were observed to correlate with advanced prostate cancer in the TRAMP model. Together these observations implicate IGF-I as an important factor during the initiation and progression of primary prostate cancer and provide evidence that there is a strong selection against expression of IGF1R and IGF2R in metastatic and androgen-independent disease.  (+info)

Phosphorylation of arylsulphatase A occurs through multiple interactions with the UDP-N-acetylglucosamine-1-phosphotransferase proximal and distal to its retrieval site by the KDEL receptor. (7/794)

Phosphorylation of oligosaccharides of the lysosomal enzyme arylsulphatase A (ASA), which accumulate in the secretions of cells that mis-sort most of the newly synthesized lysosomal enzymes due to a deficiency of mannose 6-phosphate receptors, was found to be site specific. ASA residing within the secretory route of these cells contains about one third of the incorporated [2-3H]mannose in phosphorylated oligosaccharides. Oligosaccharides carrying two phosphate groups are almost 2-fold less frequent than those with one phosphate group and only a few of the phosphate groups are uncovered. Addition of a KDEL (Lys-Asp-Glu-Leu) retention signal prolongs the residence time of ASA within the secretory route 6-fold, but does not result in more efficient phosphorylation. In contrast, more than 90% of the [2-3H]mannose incorporated into secreted ASA (with or without a KDEL retention signal) is present in phosphorylated oligosaccharides. Those with two phosphate groups are almost twice as frequent as those with one phosphate group and most of the phosphate groups are uncovered. Thus, ASA receives N-acetylglucosamine 1-phosphate groups in a sequential manner at two or more sites located within the secretory route proximal and distal to the site where ASA is retrieved by the KDEL receptor, i.e. proximal to the trans-Golgi. At each of these sites up to two N-acetylglucosamine 1-phosphate groups can be added to a single oligosaccharide. Of several drugs known to inhibit transit of ASA through the secretory route only the ionophore monensin had a major inhibitory effect on phosphorylation, uncovering and sialylation.  (+info)

Frameshift mutations at mononucleotide repeats in caspase-5 and other target genes in endometrial and gastrointestinal cancer of the microsatellite mutator phenotype. (8/794)

The majority of tumors from hereditary nonpolyposis colorectal cancer families and a subset of unselected gastrointestinal and endometrial tumors exhibit a microsatellite mutator phenotype (MMP) that leads to the accumulation of hundreds of thousands of clonal mutations in simple repeat sequences. The mutated genes with positive or negative roles in cell growth or survival in aneuploid gastrointestinal cancer (e.g., APC, K-ras, and p53) are less frequently mutated in near-diploid MMP gastrointestinal tumors. These tumors accumulate mutations in other genes, such as DNA mismatch repair hMSH3 and hMSH6, transforming growth factor-beta type II receptor, and BAX. All these genes carry, within their coding sequences, mononucleotide repeats that are preferred targets for the MMP. Endometrial carcinoma is the most common type of extracolonic neoplasia in the hereditary nonpolyposis colorectal cancer syndrome, but the spectrum of its target cancer genes is not well characterized. Here, we report that endometrial cancer of the MMP also accumulates mutations in genes that are typically mutated in gastrointestinal cancer of the mutator pathway, including BAX (55%), hMSH3 (28%), and hMSH6 (17%). We also report the detection of frameshift mutations in caspase-5, a member of the caspase family of proteases that has an (A)10 repeat within its coding region, in MMP tumors of the endometrium, colon, and stomach (28, 62, and 44%, respectively). We therefore suggest caspase-5 as a new target gene in the microsatellite mutator pathway for cancer.  (+info)

The mannose 6-phosphate/insulin-like growth factor-II (Man-6-P/IGF-II) receptor is known to cycle between the Golgi, endosomes, and the plasma membrane. In the Golgi the receptor binds newly synthesized lysosomal enzymes and transports them directly to an endosomal (prelysosomal) compartment without traversing the plasma membrane. Deletion of the carboxyl-terminal Leu-Leu-His-Val residues of the 163 amino acid cytoplasmic tail of the bovine Man-6-P/IGF-II receptor partially impaired this function, resulting in the diversion of a portion of the receptor-ligand complexes to the cell surface, where they were endocytosed. The same phenotype was observed when 134 residues of the cytoplasmic tail were deleted from the carboxyl terminus. Disruption of the Tyr24-Lys-Tyr-Ser-Lys-Val29 plasma membrane internalization signal alone had little effect on Golgi sorting, but when combined with either deletion resulted in a complete loss of this function. The mutant receptors retained the ability to recycle to ...
TY - JOUR. T1 - The insulin-like growth factor II receptor gene is mutated in genetically unstable cancers of the endometrium, stomach, and colorectum. AU - Ouyang, Hong. AU - Shiwaku, Hiromi O.. AU - Hagiwara, Hisashi. AU - Miura, Ko. AU - Abe, Tadayoshi. AU - Kato, Yo. AU - Ohtani, Haruo. AU - Shiiba, Kenichi. AU - Souza, Rhonda F.. AU - Meltzer, Stephen J.. AU - Horii, Akira. PY - 1997/5/15. Y1 - 1997/5/15. N2 - Disruption of the DNA mismatch repair system, characterized by microsatellite instability (MI), plays an important role in the course of human carcinogenesis. Repetitive sequences constitute targets for mutation in MI+ cells, and frequent mutations have indeed been reported in such regions within the transforming growth factor β receptor II (RII) gene in genetically unstable colorectal and gastric cancers. However, other genes that are targets for mutations in MI+ cells during the course of carcinogenesis have proven elusive. Because the insulin-like growth factor II receptor ...
Human serum and urine contain polypeptides which bind mannose 6-phosphate (M6P) and insulin-like growth factor II (IGF II) and crossreact with antibodies against the M6P/IGF II receptor. These polypeptides are considered to be fragments of the M6P/IGF II receptor. The major Mr approx. 205,000 fragment in serum and urine is about 10 kDa smaller in size than the membrane-associated receptor and is accompanied by minor forms with Mr values ranging from 104,000 to 180,000. The presence of receptor fragments in biological fluids indicates that shedding is one of the mechanisms contributing to the turnover of the M6P/IGF II receptor and that receptor fragments are part of the heterogenous group of serum proteins whic bind IGF II. ...
Schmidt B, Kiecke-Siemsen C, Waheed A et al. (1995). Localization of the insulin-like growth factor II binding site to amino acids 1508-1566 in repeat 11 of the mannose 6-phosphate/insulin-like growth factor II receptor. J. Biol. Chem. 270 (25): 14975-82. PMID 7797478. doi:10.1074/jbc.270.25.14975. CS1 održavanje: Eksplicitna upotreba et al. (link) ...
The study of dietary intake of vegetables and fruit and lung cancer risk in Harbin, Heilongjiang province, northeast China(b) and Tin Corporation (YTC) miners in Yunnan(c), showed a positive effect of intake of celery daily in reduced risk of lung cancer. According to Dr. Belanger JT. research, Perillyl alcohol, a monoterpene isolated from the essential oils of celery seeds, exhibited the effect of inducing apoptosis in tumor cells without affecting normal cells and reverting tumor cells back to a differentiated state in very cancer cells, including lung cancer, through increased mannose-6-phosphate/insulin-like growth factor II receptors, tissue growth factor beta receptors, Bak and decreased ras protein prenylation, ubiquinone synthesis, and induced Phase I and Phase II detoxification systems(d ...
The present study demonstrates that IR-A is a physiological receptor for IGF-II. Previously it was believed that most, if not all, biological effects of IGF-II in cells were mediated by IGF-I-R. IGF-II-R, which also binds mannose-6-phosphate residues, is devoid of tyrosine kinase activity and is not believed to have either metabolic or mitogenic signaling potential. Most studies have indicated that the IR, which is homologous to the IGF-I-R, binds IGF-II with a relatively low affinity (1 to 5% that of insulin) (45). However, there is evidence that in certain instances the IR can bind IGF-II with high affinity. Atypical IRs, which bind IGF-II with unusually high affinity, have been found in IM-9 lymphoblasts, immature erythrocytes (18), and fetal tissues (including human placenta and brain, and chicken embryo fibroblasts) (19). Furthermore, other studies suggest that during mouse fetal development, the growth promoting effect of IGF-II is mediated in part by signaling through the IR (28). By ...
The present study demonstrates that IR-A is a physiological receptor for IGF-II. Previously it was believed that most, if not all, biological effects of IGF-II in cells were mediated by IGF-I-R. IGF-II-R, which also binds mannose-6-phosphate residues, is devoid of tyrosine kinase activity and is not believed to have either metabolic or mitogenic signaling potential. Most studies have indicated that the IR, which is homologous to the IGF-I-R, binds IGF-II with a relatively low affinity (1 to 5% that of insulin) (45). However, there is evidence that in certain instances the IR can bind IGF-II with high affinity. Atypical IRs, which bind IGF-II with unusually high affinity, have been found in IM-9 lymphoblasts, immature erythrocytes (18), and fetal tissues (including human placenta and brain, and chicken embryo fibroblasts) (19). Furthermore, other studies suggest that during mouse fetal development, the growth promoting effect of IGF-II is mediated in part by signaling through the IR (28). By ...
definition of CIM6PR, what does CIM6PR mean?, meaning of CIM6PR, Cation-Independent Mannose 6-Phosphate Receptor, CIM6PR stands for Cation-Independent Mannose 6-Phosphate Receptor
Hereditary hemochromatosis is most frequently associated with mutations in HFE, which encodes a class Ib histocompatibility protein. HFE binds to the transferrin receptor-1 (TfR1) in competition with iron-loaded transferrin (Fe-Tf). HFE is released from TfR1 by increasing concentrations of Fe-Tf, and free HFE may then regulate iron homeostasis by binding other ligands. To search for new HFE ligands we expressed recombinant forms of HFE in the human cell line 293T. HFE protein was purified, biotinylated and made into fluorescently labelled tetramers. HFE tetramers bound to TfR1 in competition with Tf, but in addition we detected a binding activity on some cell types that was not blocked by Fe-Tf or by mutations in HFE that prevent binding to TfR1. We identified this second HFE ligand as the cation independent mannose-6-phosphate receptor (CI-MPR, also known as the insulin-like growth factor-2 receptor, IGF2R). HFE:CI-MPR binding was mediated through phosphorylated mannose residues on HFE. Recombinant
It is well established that dynamin is involved in clathrin-dependent endocytosis, but relatively little is known about possible intracellular functions of this GTPase. Using confocal imaging, we found that endogenous dynamin was associated with the plasma membrane, the trans-Golgi network, and a perinuclear cluster of cation-independent mannose 6-phosphate receptor (CI-MPR)-containing structures. By electron microscopy (EM), it was shown that these structures were late endosomes and that the endogenous dynamin was preferentially localized to tubulo-vesicular appendices on these late endosomes. Upon induction of the dominant-negative dynK44A mutant, confocal microscopy demonstrated a redistribution of the CI-MPR in mutant-expressing cells. Quantitative EM analysis of the ratio of CI-MPR to lysosome-associated membrane protein-1 in endosome profiles revealed a higher colocalization of the two markers in dynK44A-expressing cells than in control cells. Western blot analysis showed that ...
In the fields of biochemistry and cell biology, the cation-dependent mannose-6-phosphate receptor (CD-MPR) also known as the 46 kDa mannose 6-phosphate receptor is a protein that in humans is encoded by the M6PR gene. The CD-MPR is one of two transmembrane proteins that bind mannose-6-phosphate (M6P) tags on acid hydrolase precursors in the Golgi apparatus that are destined for transport to the lysosome. Homologues of CD-MPR are found in all eukaryotes. The CD-MPR is a type I transmembrane protein (that is, it has a single transmembrane domain with its C-termini on the cytoplasmic side of lipid membranes) with a relatively short cytoplasmic tail. The extracytoplasmic/lumenal M6P binding-domain consists of 157 amino acid residues. The CD-MPR is approximately 46 kDa in size and it both exists and functions as a dimer. The cell surface receptor for insulin-like growth factor 2 also functions as a cation-independent mannose 6-phosphate receptor. It consists of fifteen repeats homologous to the ...
The cation-independent mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R or IGF2R) traffics IGF2 and M6P ligands between pre-lysosomal and extra-cellular compartments. Specific IGF2 and M6P high-affinity binding occurs via domain-11 and domains-3-5-9, respectively. Mammalian maternal Igf2r allele expression exceeds the paternal allele due to imprinting (silencing). Igf2r null-allele maternal transmission results in placenta and heart over-growth and perinatal lethality (|90%) due to raised extra-cellular IGF2 secondary to impaired ligand clearance. It remains unknown if the phenotype is due to either ligand alone, or to both ligands. Here, we evaluate Igf2r specific loss-of-function of the domain-11 IGF2 binding site by replacing isoleucine with alanine in the CD loop (exon 34, I1565A), a mutation also detected in cancers. Igf2rI1565A/+p maternal transmission (heterozygote), resulted in placental and embryonic over-growth with reduced neonatal lethality (|60%), and long-term survival.
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1C39: Structural basis for recognition of phosphorylated high mannose oligosaccharides by the cation-dependent mannose 6-phosphate receptor.
Definition of Mannose-6-phosphate receptors with photos and pictures, translations, sample usage, and additional links for more information.
Lin SX, Mallet WG, Huang AY, Maxfield FR. Endocytosed cation-independent mannose 6-phosphate receptor traffics via the endocytic recycling compartment en route to the trans-Golgi network and a subpopulation of late endosomes ...
Analyses with the yeast two-hybrid system showed that the cytosolic tail of the human CI-MPR interacted with full-length GGA3 as well as with the ∼150-amino acid VHS domain, but not the GAT or GAE domains of GGA3 (Fig. 1C). Further analyses revealed that the CI-MPR tail interacted with the VHS domains of all three GGAs and that the CD-MPR tail interacted with the VHS domains of GGA1 and, more weakly, GGA3 (Fig. 1D). These interactions were highly specific, because neither MPR tail bound to the VHS domains of STAM1, HRS, TOM1, and TOM1L1 (Fig. 1D). Likewise, we did not detect interactions between the GGA VHS domains and the cytosolic tails of TGN38, TRP2, tyrosinase, TRP1, LAMP-2, LIMP II, low density lipoprotein (LDL) receptor, β-amyloid precursor, and transferrin receptor (Fig. 1D), which contain either tyrosine-based sorting signals or dileucine-based sorting signals devoid of acidic clusters.. Deletion of the acidic-cluster-dileucine signals from the CI-MPR and CD-MPR tails abolished ... is the marketplace for research antibodies. Find the right antibody for your research needs. Sorting of mannose 6-phosphate receptors mediated by the GGAs.
IN-ADP1.5/2.0 IN-BATT-3 IN-CF-E9677 IN-CF-F9677 IN-CF-G9677 IN-FBLOCK-96 IN-G10 IN-G20 IN-G50 IN-H2O3 -96L IN-H2O3-100C IN-H2O3-100CB IN-H2O3-96 IN-H2O3-96B IN-H2O3-H IN-H2O3-HB IN-H2O3-PRO IN-H2O3-PROB IN-H2O3-PROIII IN-H2O3-PROIIIB IN-HBLOCK-15 IN-HBLOCK-50 IN-M8RT IN-Pad3-100C IN-Pad3-3H IN-Pad3-H IN-Pad3-H-135C IN-PES-50 IN-PES-ST IN-QBLOCK-0.2 IN-QBLOCK-0.5 IN-QBLOCK-1.5 IN-QBLOCK-2.0 IN-THEATER4x4 Instrument MPR-504 Instrument MPR-506 Instrument MPS-800 Instrument MPW-30 Instrument MPW-60 Instrument MPW-WH-1 Instrument MPR-504 Instrument MPR-506 Instrument MPS-800 Instrument MPW-30 Instrument MPW-60 Instrument MPW-WH-1 IN-ADP1.5/2.0 IN-BATT-3 IN-CF-E9677 IN-CF-F9677 IN-CF-G9677 IN-FBLOCK-96 IN-G10 IN-G20 IN-G50 IN-H2O3 -96L IN-H2O3-100C IN-H2O3-100CB IN-H2O3-96 IN-H2O3-96B IN-H2O3-H IN-H2O3-HB IN-H2O3-PRO IN-H2O3-PROB IN-H2O3-PROIII IN-H2O3-PROIIIB IN-HBLOCK-15 IN-HBLOCK-50 IN-M8RT IN-Pad3-100C IN-Pad3-3H IN-Pad3-H IN-Pad3-H-135C IN
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Taken together, our results identify the IGF-Trap as a potent inhibitor of the growth of several highly aggressive carcinoma cell types. Moreover, in our hands, the tumor-inhibitory effect of the IGF-Trap was superior to that of an anti-IGFIR antibody administered at the same (or higher) concentrations, as evidenced by the complete growth arrest and/or regression of established human breast carcinomas in IGF-Trap-treated, but not in antibody-treated xenotransplanted mice. The anticancer effect of the IGF-Trap also compared favorably with IGFBP-1 that bound IGFI and IGFII with affinities comparable with the IGF-Trap but could not significantly inhibit the growth of colorectal carcinoma MC-38 liver metastases relative to untreated controls, even when administered at a 10-fold higher concentration and with higher frequency than the IGF-Trap. This greater therapeutic efficacy is probably due to several factors, namely (i) the high affinity of the IGF-Trap for IGFII that results in blockade of both ...
Recombinant protein of human mannose-6-phosphate receptor (cation dependent) (M6PR), 20 ug available for purchase from OriGene - Your Gene Company.
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TY - JOUR. T1 - Characteristics of the internalization signal in the Y543 influenza virus hemagglutinin suggest a model for recognition of internalization signals containing tyrosine. AU - Naim, Hussein Y.. AU - Roth, Michael G.. N1 - Copyright: Copyright 2005 Elsevier B.V., All rights reserved.. PY - 1994/2/11. Y1 - 1994/2/11. N2 - Several proteins, including the hemagglutinin (HA)-Y543 mutant influenza virus hemagglutinin, are internalized by clathrin-coated pits but do not have a sequence that fits a recently proposed consensus for internalization signals containing tyrosine. To determine whether or not the HA-543 signal is a degenerate form of the internalization signal found in proteins such as the transferrin receptor and mannose 6-phosphate/insulin-like growth factor (IGF) II receptor, we have mutated amino acid positions of HA-Y543 shown to be important for internalization of the two receptors. Our results indicate that the HA-Y543 mutant contains a suboptimum sequence for a ...
The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is a multifunctional transmembrane glycoprotein, which interacts with a number of molecules, including IGF-II and M6P-containing lysosomal enzymes. The receptor is widely distributed throughout the brain and is known to be involved in lysosomal enzyme trafficking, cell growth, internalization and degradation of IGF-II. In the present study, using autoradiographic, Western blotting and immunocytochemical methods, we provide the first report that IGF-II/M6P receptors are discretely distributed at all major segmental levels of the spinal cord and dorsal root ganglia of the adult rat. In the spinal cord, a high density of [125I]IGF-II binding sites was evident in the ventral horn (lamina IX) and in areas around the central canal (lamina X), whereas intermediate grey matter and dorsal horn were associated with moderate receptor levels. The dorsal root ganglia exhibited rather high density of [125I]IGF-II binding sites. ...
The interaction of soluble forms of the human cation-independent insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-IIR) with IGFs and mannosylated ligands was analyzed in real time. IGF-IIR proteins containing domains 1-15, 10-13, 11-13, or 11-12 were combined with rat CD4 domains 3 and 4. Following transient expression in 293T cells, secreted protein was immobilized onto biosensor chips. beta-Glucuronidase and latent transforming growth factor-beta1 bound only to domains 1-15. IGF-II bound to all constructs except a control, which contained a point mutation in domain 11. The affinity of domains 1-15, 10-13, 11-13, and 11-12 to IGF-II were 14, 120, 100, and 450 nm, respectively. Our data suggest that domain 13 acts as an enhancer of IGF-II affinity by slowing the rate of dissociation, but additional enhancement by domains other than 10-13 also occurs. As the receptor functions to transport ligands from either the trans-Golgi network or extracellular space to the endosomes, the interaction
TY - JOUR. T1 - Measurement of insulin-like growth factor-II in physiological fluids and tissues. II. extraction and quantification in rat tissues. AU - Lee, Wei Hua. AU - Bowsher, Ronald R.. AU - Apathy, John M.. AU - Smith, Michele C.. AU - Henry, David P.. PY - 1991/2. Y1 - 1991/2. N2 - The tissue distribution and developmental patterns of insulin-like growth factor-II (IGF-II) have not been investigated in rat tissues, primarily because of the lack of an efficient extraction method for IGF-II and a sensitive RIA. IGF- II was extracted from rat tissues by formic acid, and the extract was heated at an acidic pH and treated with acetone. The removal of binding proteins was demonstrated by fast protein liquid chromatography size exclusion column and the elimination of a dilutional bias in the RIA. Using rat IGF-II as standard, we optimized a RIA for the quantification of IGF-II in rat tissues. In adult rats, IGF-II was found in all 15 tissues examined, with the highest concentration in the ...
J:45195 Melnick M, Chen H, Buckley S, Warburton D, Jaskoll T, Insulin-like growth factor II receptor, transforming growth factor-beta, and Cdk4 expression and the developmental epigenetics of mouse palate morphogenesis and dysmorphogenesis. Dev Dyn. 1998 Jan;211(1):11-25 ...
Loss of Imprinting of Insulin-like Growth Factor-II in Wilms Tumor Commonly Involves Altered Methylation but not Mutations of CTCF or Its Binding ...
TY - JOUR. T1 - The mannose 6-phosphate receptor and the biogenesis of lysosomes. AU - Griffiths, Gareth. AU - Hoflack, Bernard. AU - Simons, Kai. AU - Mellman, Ira. AU - Kornfeld, Stuart. PY - 1988/2/12. Y1 - 1988/2/12. N2 - Localization of the 215 kd mannose 6-phosphate receptor(MPR) was studied in normal rat kidney cells. Low levels of receptor were detected in the trans Golgi network, Golgi stack, plasma membrane, and peripheral endosomes. The bulk of the receptor was localized to an acidic, reticular-vesicular structure adjacent to the Golgi complex. The structure also labeled with antibodies to lysosomal enzymes and a lysosomal membrane glycoprotein (Igp120). While lysosome-like, this structure is not a typical lysosome that is devoid of MPRs. The endocytic marker α2macroglobulin-gold entered the structure at 37°C, but not at 20°C. With prolonged chase, most of the marker was transported from the structure into lysosomes. We propose that the MPR/Igp-enriched structure is a specialized ...
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Biosynthesis of myeloperoxidase (MPO), a myeloid lysosomal hemoprotein critical for the optimal oxygen-dependent microbicidal activity of human neutrophils, is incompletely understood. The primary translation product undergoes cotranslational N-linked glycosylation with subsequent insertion of the Fe-containing prosthetic group into the peptide backbone, thereby converting the enzymatically inactive, heme- free apoproMPO into the peroxidatively active precursor, proMPO. Eventually, proMPO undergoes proteolytic processing into native, lysosomal MPO, with subunits of 59 and 13.5 Kd. We studied three unanswered questions regarding MPO biosynthesis: (1) At what point during MPO biosynthesis is the heme moiety inserted into the apoenzyme? (2) What consequences does heme-insertion have on subsequent processing events? (3) What role does the mannose-6-phosphate receptor (M6PR) system play in the delivery of MPO to the lysosome? Disruption of Golgi by brefeldin A (BFA) produced two major changes in MPO ...
Definition of mannose-6-phosphate receptors. Provided by Stedmans medical dictionary and Includes medical terms and definitions.
Arighi CN, Hartnell LM, Aguilar RC, Haft CR, Bonifacino JS. Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor ...
Elevated expression of insulin-like growth factor-II (IGF-II) is frequently observed in a variety of human malignancies, including breast, colon, and liver cancer. As IGF-II can deliver a mitogenic signal through both IGF-IR and an alternately spliced form of the insulin receptor (IR-A), neutralizing the biological activity of this growth factor directly is a potential alternative option to IGF-IR-directed agents. Using a Fab-displaying phage library and a biotinylated precursor form of IGF-II (1-104 amino acids) as a target, we isolated Fabs specific for the E-domain COOH-terminal extension form of IGF-II and for mature IGF-II. One of these Fabs that bound to both forms of IGF-II was reformatted into a full-length IgG, expressed, purified, and subjected to further analysis. This antibody (DX-2647) displayed a very high affinity for IGF-II/IGF-IIE (K(D) value of 49 and 10 pmol/L, respectively) compared with IGF-I (approximately 10 nmol/L) and blocked binding of IGF-II to IGF-IR, IR-A, a panel of ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
To maintain an intact barrier, epithelia eliminate dying cells by extrusion. During extrusion, a cell destined for apoptosis signals its neighboring cells to form and contract a ring of actin and myosin, which squeezes the dying cell out of the epithelium. Here, we demonstrate that the signal produc …
S1pr5 - S1pr5 (untagged ORF) - Rat sphingosine-1-phosphate receptor 5 (S1pr5), (10 ug) available for purchase from OriGene - Your Gene Company.
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TY - JOUR. T1 - Insulin-like growth factor-II in nonislet cell tumors associated with hypoglycemia. T2 - Increased levels of messenger ribonucleic acid. AU - Lowe, William L.. AU - Roberts, Charles T.. AU - Leroith, Derek. AU - Rojeski, Maria T.. AU - Merimee, Thomas J.. AU - Fui, Serge Teng. AU - Keen, Harry. AU - Arnold, Dagmar. AU - Mersey, James. AU - Gluzman, Sheldon. AU - Spratt, Daniel. AU - Eastman, Richard C.. AU - Roth, Jesse. PY - 1989/12. Y1 - 1989/12. N2 - The role of insulin-like growth factor-II (IGFII) in the hypoglycemia associated with nonislet cell tumors is controversial. In this study we have addressed this question by measuring the IGF-II mRNA levels in extracts of these tumors. Hybridization of a 32P-labeled IGF-II cDNA to a Northern blot of RNA from three nonislet cell tumors associated with hypoglycemia (a hemangiopericytoma, fibrosarcoma, and malignant mesenchymal tumor) demonstrated six hybridizing bands, 6.8, 5.6, 4.7, 3.6, 2.6, and 2.1 kilobases in length. These ...
The objective of this proposal is to determine the prognostic role of expression of Insulin-Like Growth factor II in breast cancer. IGF-II is a potent mitogen for breast tumor epithelium, and is expressed in the stroma of invasive breast cancers. In this study, we analyzed expression of IGF-II mRNA and protein in two separate series of patients with invasive breast cancer, and compared the result with other clinical parameters, prognostic indicators and patient outcome. IGF-II mRNA and protein expression were easily detected in the majority of the 193 cases that were informative and had complete clinical follow up. While analysis of the cases from the two data sets individually showed that IGF-II expression was associated with clinical outcome depending on hormone receptor status. However, IGF-II expression by itself was not a prognostic indicator, and the relationship with hormone receptor status was lost when the separate data sets were analyzed together. We were unable to prove our initial hypothesis
Bevan, S. J., Parry-Billings, M, Opara, Elizabeth, Liu, C. T., Dunger, D. B. and Newsholme, E. A. (1992) The effect of insulin-like growth factor II on glucose uptake and metabolism in rat skeletal muscle in vitro. Biochemical Journal, 286(2), pp. 561-565. ISSN (print) 0264-6021 ...
The retromer is a phylogenetically conserved multisubunit complex that mediates retrograde transport of transmembrane cargo from endosomes to the TGN (Seaman, 2005; Bonifacino and Rojas, 2006; Bonifacino and Hurley, 2008). The best-characterized cargo for the mammalian retromer is the cation-independent mannose 6-phosphate receptor (MPR [CI-MPR]), one of two intracellular sorting receptors that participates in the delivery of acid hydrolases to lysosomes (Kornfeld, 1992). The CI-MPR binds newly synthesized acid hydrolases at the TGN and carries them within clathrin-coated vesicles to endosomes, where the hydrolases are released for eventual transport to lysosomes. The retromer functions to retrieve the unoccupied receptors to the TGN, where they engage in further cycles of acid hydrolase sorting. Depletion of retromer subunits by RNAi prevents this retrieval, leading to rerouting of the receptors to lysosomes and consequent leakage of newly synthesized acid hydrolases into the extracellular ...
Reagents and antibodies. Mouse Laminin-1, Lipofectin, LipofectAMINE, and LipofectAMINE 2000 were purchased from Invitrogen (Carlsbad, CA). Recombinant human IGF-I or IGF-II (rhIGF-II) was purchased from R&D System, Inc. (Minneapolis, MN) or Austral Biologics (San Ramon, CA), respectively. Human FN was purified as described ( 33). Bovine serum albumin (BSA) was purchased from Sigma (St. Louis, MO). Wortmannin was purchased from Calbiochem (La Jolla, CA).. The following monoclonal antibodies (mAbs) were used: to human β1 integrin P4C10 (Chemicon, Temecula, CA), clone-18 (BD Biosciences, San Jose, CA), and TS2/16 [American Type Culture Collection (ATCC), Manassas, VA]; to chicken β1 integrin W1B10 (Sigma Chemical Co., St. Louis, MO); to human β4 integrin A9 (kindly provided by Dr. L. Shaw); to hemagglutinin 12CA5 (ATCC); to a vascular endothelial surface protein 1C10 (Life Technologies, Inc., Gaithersburg, MD); to c-myc; to β-tubulin (Sigma). The following rabbit polyclonal antibodies were ...
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Lysosomes are membrane-delimited organelles in animal cells serving as the cells main digestive compartment to which all sorts of macromolecules are delivered for degradation. They contain more than 40 hydrolases in an acidic environment (pH of about 5). After synthesis in the ER, lysosomal enzymes are decorated with mannose-6-phosphate residues, which are recognized by mannose-6-phosphate receptors in the trans-Golgi network. They are packaged into clathrin-coated vesicles and are transported to late endosomes. Substances for digestion are acquired by the lysosomes via a series of processes including endocytosis, phagocytosis, and autophagy ...
We conclude that through coincidence detection SNX1 associates with a microdomain of the early endosome-characterized by high membrane curvature and the presence of 3-phosphoinositides-from where it regulates tubular-based endosome-to-TGN retrieval of the CI-MPR.
Expression of IGF2R (CD222, CI-M6PR, CI-MPR, CIMPR, M6P-R, MPR1, MPR300, MPRI) in soft tissue tissue. Antibody staining with HPA011332 and CAB009661 in immunohistochemistry.
Expression of IGF2R (CD222, CI-M6PR, CI-MPR, CIMPR, M6P-R, MPR1, MPR300, MPRI) in bronchus tissue. Antibody staining with HPA011332 and CAB009661 in immunohistochemistry.
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This Igf1-Lr3 Protocol and workout routine has helped my personal training clients, and myself build monster calves. Train calves 3x/week and administer 100mcg Igf1-Lr3 post workout in a series of micro injections into each calve muscle spread out about 1/2 from each other. Each calve will get 10 injects each consisting of 5mcg Igf1-Lr3 per inject site. CALVE WORKOUT I find the best response from calves comes by training them 3 times a week, hitting only one exercise per
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Das IGF1R-Gen kodiert einen Rezeptor mit Tyrosinkinase-Aktivität, der insbesondere von dem Insulin-ähnlichen Wachstumsfaktor (IGF1) stimuliert werden kann. Mutationen führen zur autosomal dominanten oder rezessiven IGF1-Resistenz. Neben der Wachstumsregulation scheint der Rezeptor auch eine Bedeutung für die Steuerung der Apoptose zu besitzen. Meist kann man ihn besonders zahlreich in bosartigem Tumorgewebe finden.. ...
Before GH and IGF some of the best including arnold sculpted come of the most awesome bodies ever. I can afford IGF while on and once during pct, but
摘要 旨在研究山羊体细胞核移植对克隆后代成纤维细胞IGF2-H19基因座甲基化的影响。以奶山羊耳成纤维细胞(GFC,对照组)和克隆山羊耳成纤维细胞(CFC,试验组)为试验材料,培养至第5代时,采用细胞计数法绘制细胞生长曲线,流式细胞仪检测细胞凋亡情况,实时荧光定量PCR分析基因的表达差异,亚硫酸氢盐测序(BSP)分析差异甲基化区域的甲基化水平。结果显示,GFC和CFC组细胞的生长曲线均呈典型S型,但CFC组细胞的凋亡率显著高于GFC组(P,0.01);CFC组细胞中Dnmt1(P,0.01)、Dnmt3b(P,0.01)、 ...
4AQ0: A Bacterial Glycosidase Enables Mannose-6-Phosphate Modification and Improved Cellular Uptake of Yeast-Produced Recombinant Human Lysosomal Enzymes.
It stimulates the synthesis and release of endogenous GH, with an increase in level of insulin-like growth factor (IGF-1). The ... Tesamorelin therapy may cause glucose intolerance and increase the risk of type 2-diabetes, so it is contraindicated in ... released GH then binds with the receptors present on various body organs and regulates the body composition. This regulation is ... 3 (2): 319-20. doi:10.4103/0975-7406.80763. PMC 3103937. PMID 21687371. DeRuiter J, Holston PL. "Review of Selected NMEs 2011 ...
IGF-I, and human insulin on insulin and igf-I receptor signaling. Diabetes. 2013 Jul;62(7):2539-44. Gerstein HC, Bosch J, ... used for basal insulin support in diabetes type 1 and type 2. NPH insulins are suspensions that require shaking for ... Insulin in the form of a hexamer will not bind to its receptors, so the hexamer has to slowly equilibrate back into its ... The reason this is important is because patients, if they know they are using a different type of insulin, might behave ...
... either rendering them incapable of producing IGF-1 or unable to have adequate receptors for IGF-1 uptake. Furthermore, mice ... A-type lamins promote genetic stability by maintaining levels of proteins that have key roles in the repair processes of non- ... 2016). "Insulin and IGF-1 receptors regulate FoxO-mediated signaling in muscle proteostasis". J Clin Invest. 126 (9): 3433-3346 ... Specifically, the hormone insulin-like growth factor 1 (IGF-1), binds to a cell receptor, leading to a phosphorylation cascade ...
... in which insulin acts via the IGF-1. Therefore, deficiency of insulin or the insensitivity of its receptors play a central role ... This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of an immune-mediated ... Type 1 diabetes must be managed with insulin injections. Prevention and treatment of type 2 diabetes involves maintaining a ... This is when a type 1 diabetic becomes insulin resistant, the hallmark for type 2 diabetes or has a family history for type 2 ...
There are two types: Insulin-like growth factor 1 receptor (IGF-1R) Insulin-like growth factor 2 receptor (IGF-2R) Somatomedin+ ... A somatomedin receptor is a receptor which binds the somatomedins (IGFs). Somatomedin is abbreviated to IGF, in reference to ... Receptor at the US National Library of Medicine Medical Subject Headings (MeSH) v t e. ...
... receptor, igf type 1 MeSH D12.776.543.750.750.400.780.410 - receptor, igf type 2 MeSH D12.776.543.750.750.400.820 - receptors, ... receptor, erbb-3 MeSH D12.776.543.750.060.468 - receptor, igf type 1 MeSH D12.776.543.750.060.484 - receptor, insulin MeSH ... receptors, tumor necrosis factor, type i MeSH D12.776.543.750.705.852.760.798 - receptors, tumor necrosis factor, type ii MeSH ... activin receptors, type i MeSH D12.776.543.750.750.400.820.500.750 - activin receptors, type ii MeSH D12.776.543.750.750.400. ...
Functional interactions with the EGF receptor and the type I/type II TGFβ receptor system have also been reported, and other ... IGFBP-3 exerts antiproliferative effects in many cell types by blocking the ability of IGF-1 and IGF-2 to activate the IGF1R ( ... and block their access to the IGF-1 receptor (IGF1R), which is activated by both IGFs. IGFBP-3 also interacts with cell-surface ... it can modulate nuclear hormone receptor activity by direct binding to retinoid X receptor, retinoic acid receptor, vitamin D ...
On je transmembranski receptor koji se aktivira IGF-1 hormonom (insulinu sličan faktor rasta 1) i srodnim hormonom IGF-2. On ... "Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor.". Growth ... Surmacz E, Bartucci M (2005). "Role of estrogen receptor alpha in modulating IGF-I receptor signaling and function in breast ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7,, 3.4.21/22/23/24, ...
1996). "The type I interferon receptor mediates tyrosine phosphorylation of insulin receptor substrate 2". J. Biol. Chem. 271 ( ... Modulation by insulin growth factor-I (IGF) and enhanced IGF-I signaling". J. Biol. Chem. 271 (16): 9287-90. doi:10.1074/jbc. ... The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an ... "Modulation of insulin signal transduction by eutopic overexpression of the receptor-type protein-tyrosine phosphatase LAR". Mol ...
These types of drugs were used extensively in Major League Baseball in the 1990s and early 2000s. This is the complete list of ... Selective estrogen receptor modulators, including raloxifene, tamoxifen and toremifene are banned. Clomiphene, cyclofenil, ... IGF-1, etc.), fibroblast growth factors (FGFs), hepatocyte growth factors (HGF), mechano growth factors (MGFs), platelet- ... The most famous example of this type of doping is Lance Armstrong's performance in the Tour de France. Banned androgenic agents ...
The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large ... 4548-G05 Insulin Insulin-like growth factor 1 Mecasermin The Insulin Receptor is a type of tyrosine kinase receptor, in which ... The insulin receptor's endogenous ligands include insulin, IGF-I and IGF-II. Using a cryo-EM, structural insight into ... "Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease". ...
In C. elegans, the insulin/IGF-1/FOXO pathway is initiated by changes in IGF-1 levels which cause IGF-1 receptors to start a ... Wild type C. elegans fed a diet that included 2% glucose showed reduced Daf-16 activity and lifespan was shortened by 20% ... identical to the IGF-1 receptor, which regulates growth; and 33% identical to the human insulin receptor-related receptor. ... The protein predicted from DAF-2's sequence is 35% identical to the human insulin receptor, which regulates metabolism; 34% ...
IGF-1 receptors are ubiquitous, which allows for metabolic changes caused by IGF-1 to occur in all cell types. IGF-1's ... IGF-1 binds to at least two cell surface receptor tyrosine kinases: the IGF-1 receptor (IGF1R), and the insulin receptor. Its ... IGF-1 binds and activates its own receptor, IGF-1R, through the cell surface expression of Receptor Tyrosine Kinase's (RTK's) ... The IGF-1 receptor seems to be the "physiologic" receptor because it binds IGF-1 with significantly higher affinity than ...
January 2016). "mTORC2 promotes type I insulin-like growth factor receptor and insulin receptor activation through the tyrosine ... Grb10, a negative regulator of insulin/IGF-1 receptor signaling upstream of Akt and mTORC2, is phosphorylated and therefore ... mTORC2 has tyrosine kinase activity and phosphorylates IGF-IR and insulin receptor at the tyrosine residues Y1131/1136 and ... In many types of human cancer, hyperactivation of mTORC2 caused by mutations and aberrant amplifications of mTORC2 core ...
Tarceva is a small molecule inhibitor of the epidermal growth factor receptor (EGFR) and is the only EGFR inhibitor to have ... Though oncology was the top priority for OSI, research and development targeting type 2 diabetes and obesity was conducted ... Companies portal Linsitinib (OSI-906), an inhibitor of IGF-1R in clinical trials for cancer treatment Kristi Park. "OSI ...
"Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer's disease indicate possible resistance to IGF-1 and ... Like apoptosis and other types of programmed cell death, the cell is involved in causing its own death, and gene expression is ... The group used human insulin-like growth factor 1 receptor (IGF-1R) to stimulate cell death in 293T cells and mouse embryonic ... This IGF-1R induced neurodegeneration was caused by both paraptosis and autophagic cell death. IGF-1R is an important area of ...
As with other members of the superfamily, activins interact with two types of cell surface transmembrane receptors (Types I and ... Inhibin secretion is diminished by GnRH, and enhanced by insulin-like growth factor-1 (IGF-1). It is secreted from the Sertoli ... Activin type 1 receptors: ACVR1, ACVR1B, ACVR1C Activin type 2 receptors: ACVR2A, ACVR2B Activin binds to the Type II receptor ... and activation of Type I activin receptor. This then interacts with and then phosphorylates SMAD2 and SMAD3, two of the ...
Cluster of differentiation IGF-1 Receptor Mannose 6-phosphate receptor GRCh38: Ensembl release 89: ENSG00000197081 - Ensembl, ... mapping of the gene for the type II insulin-like growth factor receptor/cation-independent mannose 6-phosphate receptor in man ... Scott CD, Firth SM (2005). "The role of the M6P/IGF-II receptor in cancer: tumor suppression or garbage disposal?". Horm. Metab ... "Mannose 6-Phosphate/Insulin-like Growth Factor-II Receptor Targets the Urokinase Receptor to Lysosomes via a Novel Binding ...
It is a type of mitogen which is specific only to the receptors on certain types of cells. GH is a 191-amino acid, single-chain ... IGF-1 has growth-stimulating effects on a wide variety of tissues. Additional IGF-1 is generated within target tissues, making ... Thus, GH exerts some of its effects by binding to receptors on target cells, where it activates the MAPK/ERK pathway.[35] ... GH also stimulates production of IGF-1 and increases the concentration of glucose and free fatty acids.[1][2] ...
IGF-1) and cancer and is the current recipient of an NCI grant to study the relationship between cancer and type 2 diabetes. He ... PMID 19716998 Physical and functional interaction between polyoma virus middle T antigen and insulin and IGF-I receptors is ... Vijayakumar A, Novosyadlyy R, Wu Y, Yakar S, Leroith D. Growth Horm IGF Res. 30 September 2009. doi:10.1016/j.ghir.2009.09.002 ... He is an international expert in insulin-like growth factor-1 (IGF-1). LeRoith was the first to demonstrate the link between ...
... and has greater blood flow and more receptors for cortisol than peripheral fat. The greater the number of cortisol receptors, ... Also, in case the waist is convex rather than concave, such as is the case in pregnancy, different body types, and obesity, the ... Growth Hormone and IGF Research. 23 (5): 196-199. doi:10.1016/j.ghir.2013.07.001. PMID 23890535. Falhammer, H (2011). " ... and hypertension in type 2 diabetes. The stress hormone cortisol is regulated by the hypothalamic-pituitary-adrenal (HPA) axis ...
... it connects to the insulin receptors already present, that is tyrosine kinase receptor. These receptors have two alpha subunits ... including R-Type) and the T-type Ca+2 channels. There are two phases of the insulin secretion, the first phase involves the L- ... IGF-I). IGF-I, in turn, suppresses the insulin secretion. After insulin enters the bloodstream, it binds to a membrane-spanning ... The α-subunits act as insulin receptors and the insulin molecule acts as a ligand. Together, they form a receptor-ligand ...
IGF-1 binds to at least two cell surface receptors: the IGF1 Receptor (IGFR), and the insulin receptor. The IGF-1 receptor ... "Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor". Growth ... Like the insulin receptor, the IGF-1 receptor is a receptor tyrosine kinase - meaning it signals by causing the addition of a ... The receptor is a member of a family which consists of the insulin receptor and the IGF-2R (and their respective ligands IGF-1 ...
In vitro data suggests this co-stimulation leads to increased Th1 type cytokine release of IFN-γ and IL-2 that further ... and its receptor, bFGF and IL-6 appear to be required for endothelial cell migration during angiogenesis. Thalidomide and its ... single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast ... concentrations in immune and non-immune cell types, partially inhibiting the production of many pro-inflammatory cytokines such ...
Höpfner M, Huether A, Sutter AP, Baradari V, Schuppan D, Scherübl H (2006). "Blockade of IGF-1 receptor tyrosine kinase has ... The nodular type may be solitary (large mass) or multiple (when developed as a complication of cirrhosis). Tumor nodules are ... Inhibition of IGF-1R tyrosine kinase (IGF-1R-TK) by NVP-AEW541 induces growth inhibition, apoptosis and cell cycle arrest in ... Thus, IGF-1R-TK inhibition may be a promising novel treatment approach in HCC. Huynh H, Chow PK, Ooi LL, Soo KC (2002). "A ...
Dutasteride is a medication in the same class as finasteride but inhibits both type I and type II 5-alpha reductase. ... Androgens have different effects at different follicles: they stimulate IGF-1 at facial hair, leading to growth, but can also ... The mechanism by which the androgen receptor triggers dermal papilla permanent senescence is not known but may involve IL6, ... The type or quantity of exercise may influence hair loss. Testosterone levels are not a good marker of baldness, and many ...
... signalling by regulating the amount of insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF-1R) on the cell ... regulating tumour suppressor proteins is consistent with the frequent overexpression of NEDD4 in many different types of human ... "Upregulation of the E3 ligase NEDD4-1 by oxidative stress degrades IGF-1 receptor protein in neurodegeneration". J. Neurosci. ... such as HER3 and HER4 EGF receptors, and ACK. The fibroblast growth factor receptor 1 (FGFR1) undergoes NEDD4 mediated ...
Igf-1) and type 1 IGF receptor (Igf1r)". Cell. 75 (1): 59-72. doi:10.1016/s0092-8674(05)80084-4. ISSN 0092-8674. PMID 8402901. ... One example of a null allele is the 'O' blood type allele in the human A, B and O blood type system. The alleles for the A- ... The experiments only differed in the gene being investigated, Igf-1 and Igf-2. Both experiments used the process of mutageneis ... The experiment involving Igf-1 revealed that, in addition to its role after birth, it is also fundamental in the development of ...
She showed that the brain produced more IGF-II when it is making memories, and that by increasing the amount of IGF-II it is ... a type of sea slug). Her early work involved investigations into the impact of the insulin-like growth factor 2 (IGF-II) ... where she studied T-cell antigen receptors. In 1985 she got a post-doctoral research fellowship at the Dana-Farber Cancer ... Similarly, she demonstrated that blocking the increase of IGF-II stopped the formation of long-term memory. She has continued ...
Scott CD, Firth SM (2005). "The role of the M6P/IGF-II receptor in cancer: tumor suppression or garbage disposal?". Horm. Metab ... mapping of the gene for the type II insulin-like growth factor receptor/cation-independent mannose 6-phosphate receptor in man ... Receptor insulinu sličnog faktora rasta 2 (IGF2R, katjionski nezavisni receptor manoza-6-fosfata, CI-MPR) je protein koji je ... "Mannose 6-Phosphate/Insulin-like Growth Factor-II Receptor Targets the Urokinase Receptor to Lysosomes via a Novel Binding ...
C. acnes' ability to bind and activate a class of immune system receptors known as toll-like receptors (TLRs), especially TLR2 ... High levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are also associated with worsened acne.[42] Both ... Many over-the-counter treatments in many forms are available, which are often known as cosmeceuticals.[168] Certain types of ... Flutamide, a pure antagonist of the androgen receptor, is effective in treating acne in women.[112][120] It appears to reduce ...
It may also be used to treat and prevent certain types of thyroid tumors.[1] It is not indicated for weight loss.[1] ... T4 and T3 bind to thyroid receptor proteins in the cell nucleus and cause metabolic effects through the control of DNA ... 20 (2): 300-13. doi:10.1042/bj0200300. PMC 1251714 . PMID 16743659.. *^ a b King, Tekoa L.; Brucker, Mary C. (2010). ... doi:10.1186/1745-0179-2-23. PMC 1584230 . PMID 16968542.. *^ Sherwood, Lauralee (2010). "19 The Peripheral Endocrine Glands". ...
It is mainly used to treat cases of NSCLC that harbour mutations in the epidermal growth factor receptor (EGFR) gene.[5] ... Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... trial in people with NSCLC suggested the drug extended life expectancy in stage IV NSCLC adenocarcinoma with EGFR Mutation type ... Afatinib covalently binds to cysteine number 797 of the epidermal growth factor receptor (EGFR) via a Michael addition (IC50 = ...
The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and ... Certain types of physical exercise have been shown to markedly (threefold) increase BDNF synthesis in the human brain, a ... Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... receptor binding. • neurotrophin TRKB receptor binding. • growth factor activity. • GO:0001948 protein binding. ...
... a type of cell surface receptor. Two types of PDGFRs have been identified: alpha-type and beta-type PDGFRs.[8] The alpha type ... Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... The receptor for PDGF, PDGFR is classified as a receptor tyrosine kinase (RTK), ... Like many other growth factors that have been linked to disease, PDGF and its receptors have provided a market for receptor ...
Less typical side effects are those of the cardiovascular system, such as high blood pressure, various types of arrhythmia, and ... Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture). See also. Receptor/signaling modulators. ... 46 (2): 101-110. doi:10.1046/j.1365-2125.1998.00764.x. ISSN 0306-5251. PMC 1873672. PMID 9723817.. ...
GH induction of IGF-1 production and secretion occurs in almost all types of tissue in the body, but especially in the liver, ... similarly to the insulin-like growth factor-1 receptor (IGF-1R),[1] been found to be essential for mammary gland development.[ ... while IGF-1, in contrast, has been found to not do this.[12][13] In addition to estrogen and GH/IGF-1 both being essential for ... including IGF-1, IGF-2, amphiregulin,[65] EGF, FGF, hepatocyte growth factor (HGF),[66] tumor necrosis factor α (TNF-α), tumor ...
... which is rich in IGF-1, can be a useful part of a weight reduction program.[citation needed] Although IGF-1 is not absorbed ... This gene is also one the determining factors in wet or dry type earwax, as the mammary glands are a form of apocrine gland.[34 ... Staley, T. E.; Bush, L. J. (1985). "Receptor mechanisms of the neonatal intestine and their relationship to immunoglobulin ... IGF-1), IGF-binding protein-3, insulin, and growth hormone". Metabolism. 43 (3): 315-9. doi:10.1016/0026-0495(94)90099-X. PMID ...
GH supplementation is not recommended medically for the physiologic age-related decline in GH/IGF secretion.[7][11] It may be ... Insensitivity to GH is traditionally termed Laron dwarfism, but over the last 15 years many different types of GH resistance ... have been identified, primarily involving mutations of the GH binding protein or receptors. ... Indirect hormonal criteria (IGF levels from a single blood sample). *Direct hormonal criteria (measurement of GH in multiple ...
Höppener JW, Ahrén B, Lips CJ (August 2000). "Islet amyloid and type 2 diabetes mellitus". N. Engl. J. Med. 343 (6): 411-9. doi ... Sva tri kompleksa sadrže kalcitoninski receptor u jezgri, plus jedan od tri proteina koji modificiraju aktivnost receptora, ... From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus". Diabetes. 58 (4): 773 ... Lorenzo A, Razzaboni B, Weir GC, Yankner BA (April 1994). "Pancreatic islet cell toxicity of amylin associated with type-2 ...
The binding potential of 5-HT2A receptors and 5-HT1A receptors have been reportedly decreased and increased respectively in a ... Binge-eating/purging type: the individual utilizes binge eating or displays purging behavior as a means for losing weight.[80] ... Støving RK, Chen JW, Glintborg D, Brixen K, Flyvbjerg A, Hørder K, Frystyk J (2007). "Bioactive insulin-like growth factor (IGF ... Restricting type: the individual uses restricting food intake, fasting, diet pills, or exercise as a means for losing weight;[ ...
"Press Announcements - FDA approves Zydelig for three types of blood cancers". Archived from the original on 2016- ... The role of PI-3-kinase in anabolic signaling by insulin, IGF-1, and other growth factors makes a straightforward link between ... on growth factor receptors or adaptor proteins via the pY-X-X-M motif.[13][14] ... In 1997, the Cantley lab discovered that the enzymes that had been referred to as type II PIP-kinases, instead of using PtdIns( ...
... implications for IGF and IGF-I receptor interactions". EMBO J. 17 (22): 6558-72. PMC 1171003. . PMID 9822601. doi:10.1093/emboj ... type B pancreatic cell proliferation. • cellular response to cAMP. • توصيل الإشارة. • mammary gland involution. • شيخوخة. • ... Schneider MR، Wolf E، Hoeflich A، Lahm H (2002). "IGF-binding protein-5: flexible player in the IGF system and effector on its ... Twigg SM، Baxter RC (1998). "Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs ...
transmembrane receptor protein tyrosine kinase activator activity. • epidermal growth factor receptor binding. • Wnt-protein ... embryonic retina morphogenesis in camera-type eye. • positive regulation of gene expression. • positive regulation of cell ... Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... positive regulation of receptor internalization. • positive regulation of epidermal growth factor-activated receptor activity. ...
The oxytocin receptor is a G-protein-coupled receptor that requires magnesium and cholesterol. It belongs to the rhodopsin-type ... oxytocin receptor binding. • hormone activity. • neurohypophyseal hormone activity. • neuropeptide hormone activity. Cellular ... Estrogen has been found to increase the secretion of oxytocin and to increase the expression of its receptor, the oxytocin ... Cardiac effects: oxytocin and oxytocin receptors are also found in the heart in some rodents, and the hormone may play a role ...
2000). „Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins". J. Cell. Sci. ENGLAND. 113 (19): 3473-84. ISSN ... Heavner GA, Audhya T, Goldstein G (1990). „Peptide analogs of thymopentin distinguish distinct thymopoietin receptor ... IGF-1, IGF-2) ... Lamina-associated polypeptide 2alpha binds intranuclear A-type ... 2]. Timopoietin (polipeptid vezan za laminu 2, LAP2) je protein koji je kod ljudi kodiran TMPO genom.[1][2] LAP2 je protein ...
"Trk" family of Tyrosine kinases receptors.[14] Types[edit]. Nerve growth factor[edit]. Main article: Nerve growth factor ... Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... Receptors[edit]. Main article: Nerve growth factor receptor. There are two classes of receptors for neurotrophins: p75 and the ... given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC and TrkB). Mice born without the ...
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 (/ˌbrækəˈwʌn/) gene.[5] ... androgen receptor binding. • RNA binding. • ubiquitin protein ligase binding. • transcription regulatory region DNA binding. • ... "Functional and physical interactions between BRCA1 and p53 in transcriptional regulation of the IGF-IR gene". Horm. Metab. Res ... androgen receptor signaling pathway. • negative regulation of centriole replication. • postreplication repair. • Lipid ...
It was previously thought that particular types of pituitary tumors were more prone to apoplexy than others, but this has not ... and a hormonal panel including IGF-1, growth hormone, prolactin, luteinizing hormone, follicle-stimulating hormone, thyroid- ... Androgen receptor (Androgen insensitivity syndrome). *general: Hypogonadism (Delayed puberty). *Hypergonadism *Precocious ... 4 (2): 143-7. doi:10.1023/A:1022938019091. PMID 12766542.. *^ Fernández-Balsells MM, Murad MH, Barwise A, et al. (April 2011 ...
... meaning that they bind to a cell in a way that regulates LHRH receptors. The process of inhibiting the cell receptors suggests ... July 2002). "D-Amino acid residue in the C-type natriuretic peptide from the venom of the mammal, Ornithorhynchus anatinus, the ... Antibodies: Xentuzumab (against IGF-1 and IGF-2). Kisspeptin. *Agonists: Kisspeptin. *Kisspeptin-10 ... B-type Natriuretic Peptide (BNP) - produced in myocardium & useful in medical diagnosis ...
... hippocampal IGF gene expression (47), and serum levels of both IGF (178) and VEGF (63). IGF-1 and VEGF, apparently produced in ... Type of adaptation Endurance. training effects Strength. training effects Sources Skeletal muscle morphology and exercise ... Berry MD (2007). "The potential of trace amines and their receptors for treating neurological and psychiatric diseases". Rev ... Physical exercises are generally grouped into three types, depending on the overall effect they have on the human body:[4] ...
"Type 1 T helper and type 2 T helper cells: functions, regulation and role in protection and disease". International Journal of ... Radoja S, Frey A, Vukmanovic S (2006). "T-cell receptor signaling events triggering granule exocytosis". Crit Rev Immunol. 26 ( ... Selain itu, DETC mempercepat perbaikan jaringan dengan mensekresi faktor pertumbuhan dan sitokin seperti IGF-1, KGF-1 (FGF-7), ... 2005). "Type II secretion: a protein secretion system for all seasons". Trends Microbiol. 13 (12): 581-8. PMID 16216510.. ...
The main type of cells that make up the epidermis are Merkel cells, keratinocytes, with melanocytes and Langerhans cells also ... Also located within the reticular region are the roots of the hairs, sebaceous glands, sweat glands, receptors, nails, and ... consumption increase IGF-1 generation which in turn increases sebum production.[7] Overwashing the skin does not cause sebum ... The main type of cells that make up the epidermis are keratinocytes, melanocytes, Langerhans cells, and Merkel cells. The ...
Blum G, Gazit A, Levitzki A (2000). "Substrate competitive inhibitors of IGF-1 receptor kinase". Biochemistry. 39 (51): 15705- ... pancreatic cancer and several other types of cancer. It is a receptor tyrosine kinase inhibitor, which acts on the epidermal ... Other cases of resistance can involve numerous mutations, including recruitment of a mutated IGF-1 receptor to dimerise with ... which was the first drug of this type. Erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine ...
... can bind type I TGF-beta superfamily receptors ACVR1B (ALK4), TGFBR1 (ALK5) and ACVR1C (ALK7), but predominantly uses ... restores the insulin/IGF‐1 signaling pathway, and stimulates adiponectin secretion from white adipose tissue by direct action ... Receptor/signaling modulators. Signaling peptide/protein receptor modulators. Growth factor receptor modulators. Cytokine ... camera-type eye morphogenesis. • anterior/posterior pattern specification. • negative regulation of cell proliferation. • SMAD ...
... acts as a selective estrogen receptor modulator (SERM), or as a partial agonist of the estrogen receptors (ERs). It ... Tamoxifen has been found to decrease insulin-like growth factor 1 (IGF-1) levels by 17 to 38% in women and men.[74] Suppression ... The American Cancer Society lists tamoxifen as a known carcinogen, stating that it increases the risk of some types of uterine ... Selective estrogen receptor modulator activityEdit. Crystallographic structure of afimoxifene (carbon = white, oxygen = red, ...
... and has greater blood flow and more receptors for cortisol than peripheral fat. The greater the number of cortisol receptors, ... Growth Hormone and IGF Research. 23 (5): 196-199. doi:10.1016/j.ghir.2013.07.001. PMID 23890535.. ... multicentric study in type 2 diabetes mellitus patients]". Arq Bras Endocrinol Metabol (in Portuguese). 51 (3): 443-9. PMID ... Pedersen, SB; Jonler, M; Richelsen, B (1994). "Characterization of regional and gender differences in glucocorticoid receptors ...
Receptor/signaling modulators. Estrogens and antiestrogens. Androgen receptor modulators. Progesterone receptor modulators. ... and estrus-type changes (including vaginal, uterine, and mammary gland changes and sexual receptivity) in sexually immature, ... The estrogen receptor, as well as the progesterone receptor, have been detected in the skin, including in keratinocytes and ... Estradiol acts primarily as an agonist of the estrogen receptor (ER), a nuclear steroid hormone receptor. There are two ...
signaling receptor activity. • transmembrane receptor protein tyrosine kinase activity. • receptor tyrosine kinase. • ... activation of cysteine-type endopeptidase activity involved in apoptotic process. • response to drug. • signal transduction. • ... Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... The co-receptors themselves are classified as members of the GDNF receptor-α (GFRα) protein family. Different members of the ...
Insulin-like growth factor type-I receptor (IGF-1R) dependent phosphorylation of ERK1/2 but not Akt (PKB) can be induced by ... Insulin-like growth factor type-I receptor (IGF-1R) dependent phosphorylation of ERK1/2 but not Akt (PKB) can be induced by ... Insulin-like growth factor type-I receptor (IGF-1R) dependent phosphorylation of ERK1/2 but not Akt (PKB) can be induced by ... Insulin-like growth factor type-I receptor (IGF-1R) dependent phosphorylation of ERK1/2 but not Akt (PKB) can be induced by ...
Major molecular abnormalities in breast cancer include the deregulation of several components of the IGF system. It is well ... Immunological studies of type I IGF receptors and insulin receptors: characterisation of hybrid and atypical receptor subtypes ... Breast cancer Insulin receptor IGF-I receptor IGF-I IGF-II IGF system ... Novel human monoclonal antibodies to insulin-like growth factor (IGF)-II that potently inhibit the IGF receptor type I signal ...
Receptor, IGF Type 2. Secondary source ID. *GENBANK/L06445. *GENBANK/L06446. *GENBANK/M97300 ... Publication types, MeSH terms, Substance, Secondary source ID. Publication types. *Research Support, Non-U.S. Govt ... The mouse insulin-like growth factor type 2 receptor (Igf2r) is imprinted and expressed exclusively from the maternally ... Methylation of region 2 may mark the maternal Igf2r locus in a manner that could act as an imprinting signal. These data ...
Type 2 diabetes (T2D) is a modern socioeconomic burden, mostly due to its long-term complications affecting nearly all tissues ... Moloney AM, Griffin RJ, Timmons S, OConnor R, Ravid R, ONeill C (2010) Defects in IGF-1 receptor, insulin receptor and IRS-1/ ... Brain GLP-1/IGF-1 Signaling and Autophagy Mediate Exendin-4 Protection Against Apoptosis in Type 2 Diabetic Rats. ... glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. doi: 10.1016/S0140- ...
The perinatal mortality (,80%) observed in homozygotes (Igf2rI1565A/I1565A) suggested that wild-type paternal allele expression ... The cation-independent mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R or IGF2R) traffics IGF2 and M6P ... IGF-II) receptor reduces organ size by IGF-II-mediated and IGF-II-independent mechanisms. J Biol Chem 273, 28610-28616 (1998). ... Comparison of wild-type and heterozygote Igf2rI1565A/+p, (p = 0.0043), and comparison of wild-type and homozygote Igf2rI1565A/ ...
T1 - Analysis of insulin-like growth factors (IGF)-I, and -II, type II IGF receptor and IGF-binding protein-2 mRNA and peptide ... Analysis of insulin-like growth factors (IGF)-I, and -II, type II IGF receptor and IGF-binding protein-2 mRNA and peptide ... Analysis of insulin-like growth factors (IGF)-I, and -II, type II IGF receptor and IGF-binding protein-2 mRNA and peptide ... Analysis of insulin-like growth factors (IGF)-I, and -II, type II IGF receptor and IGF-binding protein-2 mRNA and peptide ...
2003). IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation. N. Engl. J. Med. 349, 2211-2222. ... receptor type C was higher in control males than control females in the liver, but higher in control females than control males ... Serotonin 1B receptor has a range of effects on both behavior and physiology (Donaldson et al., 2013), though its role in ... Serotonin 1B receptor expression is upregulated by mineralcorticoids in the aorta of rats (Banes and Watts, 2002); thus, ...
To test the possibility that soluble receptor can therefore modulate the activity of IGF-II, we determined the effect of ... receptor is released from cultured cells and tissues in a soluble form that retains its affinity for IGF-II. ... Receptor, IGF Type 2 * Epidermal Growth Factor * Insulin-Like Growth Factor II ... These results suggest that soluble IGF-II/M6P receptor not only plays a role in modulating the action of IGF-II but may also ...
Mannose 6-phosphate receptors (MPRs) transport newly synthesized lysosomal hydrolases from the Golgi to prelysosomes and then ... Receptor, IGF Type 2 / metabolism* * Recombinant Fusion Proteins / metabolism * Vesicular Transport Proteins ... TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking Cell. 1998 May 1;93(3):433-43. doi: 10.1016/s0092- ... Mannose 6-phosphate receptors (MPRs) transport newly synthesized lysosomal hydrolases from the Golgi to prelysosomes and then ...
Down-regulation of type I insulin-like growth factor receptor increases sensitivity of breast cancer cells to insulin. Cancer ... InsR heterodimerizes with the highly homologous IGF-I receptor (IGF-IR), which also binds IGF-I and IGF-II (2). ... IGF-I and IGF-II bind heterodimers and IGF-IR homodimers with high affinity, whereas insulin binds InsR homodimers but not IGF- ... IGF-IR, and AKT. In contrast, MAB391 blocked IGF-I-induced activation of IGF-IR, modestly decreased IGF-I-induced P-AKT, but ...
... and clinical studies related to type 1 and type 2 diabetes. The journal welcomes submissions focusing on the epidemiology, ... Activation of the intrinsic kinase activity of the IGF-I receptor (IGF-IR) is required to trigger downstream signaling events ... J. Haylor, H. Hickling, E. E. L. Eter et al., "JB3, an IGF-I receptor antagonist, inhibits early renal growth in diabetic and ... People with both type 1 and type 2 diabetes develop atherosclerosis at a significantly accelerated rate compared to non ...
Prior insulin-like growth factor receptor (IGF-1R). *Prior investigational agent within 21 days prior to randomization ... Type 1 diabetes mellitus or Type 2 diabetes mellitus currently requiring insulinotropic or insulin therapy ... Study Type:. Interventional Study Design:. Allocation: Randomized. Intervention Model: Parallel Assignment. Masking: Quadruple ... Use of H2-receptor antagonists such as ranitidine are not excluded. *History of cerebrovascular accident (CVA) within 180 days ...
The newly identified resistin receptor, CAP1, was expressed across a large panel of breast cancer cell lines and primary breast ... The newly identified resistin receptor, CAP1, was expressed across a large panel of breast cancer cell lines and primary breast ... CAP1 was associated with poor tumor characteristics with higher CAP1 expression among estrogen receptor (ER)-negative tumors, ... CAP1 was associated with poor tumor characteristics with higher CAP1 expression among estrogen receptor (ER)-negative tumors, ...
Although commonly referred to as the IGF-I receptor, it binds both IGF-I and IGF-II with high affinity. It is comprised of a ... A protein-tyrosine kinase receptor that is closely related in structure to the INSULIN RECEPTOR. ... IGF I Receptor; IGF-1 Receptors; Insulin Like Growth Factor I Receptor; Receptor, IGF I; Receptor, IGF-1; Receptors, IGF 1; IGF ... IGF 1 Receptor; Receptor, IGF Type 1; IGF-1 Receptor; Insulin-Like-Growth Factor I Receptor; Receptor, IGF Type 1 alpha Subunit ...
IRS-1 is the major substrate of insulin receptor and IGF-1 receptor tyrosine kinases. To clarify the physiological roles of IRS ... These authors also intercrossed mice heterozygous for null alleles of the genes for the IGF-1 receptor and IRS-2 (26), and they ... These animals were also resistant to the glucose-lowering effects of insulin, IGF-1, and IGF-2. Despite their insulin ... thus establishing a role for the IGF-1 receptor in β cells. Evidently, IRS-2 integrates the effects of insulin in peripheral ...
For example, deletion of the insulin and IGF-1 receptors from β cells or manipulation of IRS1/2 and AKT isoforms in mice ... Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited. Survey and synthesis of pathology ... Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11(2):98-107.. View this article via: PubMed CrossRef Google ... β Cell dysfunction during progression of metabolic syndrome to type 2 diabetes. Laura I. Hudish,1 Jane E.B. Reusch,2 and Lori ...
... angiotensin type 1 receptor; AT2R, angiotensin type 2 receptor; FoxO, forkhead box O; GAPDH, glyceraldehyde-3-phosphate ... dehydrogenase; IGF-1, insulin-like growth factor-I; MHC, myosin heavy chain; RAS, renin-angiotensin system; UPS, ubiquitin- ... Angiotensin-(1-7) decreases skeletal muscle atrophy induced by angiotensin II through a Mas receptor-dependent mechanism. ... Angiotensin-(1-7) [Ang-(1-7)], through its receptor Mas, produces the opposite effects than AngII. We assessed the effects of ...
2019 May 2;177(4):896-909.e20. doi: 10.1016/j.cell.2019.02.017. Epub 2019 Apr 25. ... Insulin and IGF-1 Receptor Expression throughout the SCN, Related to (A) Immunohistochemistry for the IGF-1 receptor and (B) ... straight line fit, type 0 PRC) or 10 nM insulin (n = 6, p = 0.025, straight line vs. cubic fit, type 1 PRC).. (G) Dose-response ... Insulin and IGF-1 receptor signaling is sufficient to determine essential circadian parameters, principally via increased ...
Insulin stimulates the clonogenic potential of angiogenic endothelial progenitor cells by IGF-1 receptor dependent signalling. ... Both type 1 and type 2 diabetes are associated with a significant reduction of circulating EPCs (9,10), which parallels the ... Endothelial dysfunction in type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis 2006; 16( Suppl. 1): S39- S45. ... Type 2 diabetes is characterized by a two- to fourfold increased risk of cardiovascular disease (CVD) (1). This is generally ...
... many cell types including neurons express IGFBP-7. The receptor is targeted by IGF-1, IGF-2 and Insulin (Oh et al. 1996; Ruan ... The IS circuit in fruit flies is discussed as an evolutionary ancestor of its vertebrate pendant with insulin and IGF signaling ... Best understood is the Insulin receptor (InR), a membrane bound protein dimer with extracellular alpha and intracellular beta ... 2016). IGFBPs are considered scavenger receptors to deactivate hormones or are described as complexing factors that stabilize ...
LCN2 binds at least two mammalian surface receptors, LCN2 receptor (also known as 24p3R, NGALR, or SLC22A17), a brain-type ... tyrosine kinase-like orphan receptor-1 (ROR1) in 3T3-L1 cells, or insulin-like growth factor 1 receptor (IGF-1R) in fibroblasts ... "The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors," Proceedings of the ... chemokine-like receptor 1), GPR1 (G protein-coupled receptor 1), and CCRL2 (chemokine (CC motif) receptor-like 2). The latter ...
... ligands inhibit breast cancer cell responses to IGFs, suggesting that targeting AHR may have benefit in cancers whose ... and the insulin receptor (IR) are receptor tyrosine kinases (RTKs) that are expressed in cancer cells. The results of different ... and the insulin receptor (IR) are receptor tyrosine kinases (RTKs) that are expressed in cancer cells. The results of different ... Our recent reports indicate that pharmacological aryl hydrocarbon receptor (AHR) ligands inhibit breast cancer cell responses ...
VEGF-A, VEGF-D, VEGF receptor-1, VEGF receptor-2, NFkB and RAGE in atherosclerotic lesions of diabetic Watanabe Heritable ... IGF-II) in pancreatic β-cells. IGF-II transgenic LDLR−/− ApoB100/100 mice exhibited insulin resistance and hyperglycemia ... We compared the impact of hyperglycemia on the risk of CVD mortality between patients with type 1 and type 2 diabetes (56). An ... Similarity of the impact of type 1 and type 2 diabetes on cardiovascular mortality in middle-aged subjects. Diabetes Care 2008 ...
Insulin and insulin-like growth factor-I (IGF-I) receptor overexpression in breast cancers leads to insulin/IGF-I hybrid ... 19 for wild-type and n = 16 A-ZIP/F-1 mice) and IGF-I (n = 9 for wild-type and n = 17 for A-ZIP/F-1 mice). Columns, mean; bars, ... IGF-II binding to insulin receptor isoform A induces a partially different gene expression profile from insulin binding. Ann N ... Skin carcinogenesis in A-ZIP/F-1 fatless and wild-type mice (A and B). ▪, A-ZIP/F-1 fatless (n = 14); □, wild-type mice (n = 10 ...
Changes in plasma testosterone and IGF-1, SkM androgen receptor mRNA, SkM IGF-1mRNA and SkM IGF-1 receptor mRNA by quantitative ... Twenty-four subjects (12 men and 12 women), including 12 with type 2 diabetes and 12 nondiabetics were enrolled. Venous blood ... Plasma IGF-1 and SkM expression of IGF-1 and IGF-1 receptor were also similar between males and females. Following ... and IGF-1 (1·72 ± 0·29 vs. 1·06 ± 0·14, P < 0·05) mRNA, but no change in expression of the IGF-1 receptor. Plasma testosterone ...
IGF-1) receptor (IGF1R). In preadipocytes deficient in LRP5, insulin-dependent phosphorylation of GSK-3β, Akt, and ERK1/2 was ... reduced in extent compared with that in wild-type cells; however, loss of LRP5 had no effect on IGF-1-dependent phosphorylation ... is mediated by Frizzled receptors and the co-receptors low-density lipoprotein receptor-related protein 5 (LRP5) and LRP6. ... Wnt3a-dependent phosphorylation of Akt was blocked in cells deficient in both the insulin receptor (IR) and the insulin-like ...
... the upstream signaling and the downstream targets involved in cardiac autophagy regulation during obesity and type 2 diabetes ... The findings are of significant importance as they demonstrate for the first time the contribution of IGF-1 receptors (IGF-1R) ... Activation of IGF-1 receptors and Akt signaling by systemic hyperinsulinemia contributes to cardiac hypertrophy but does not ... Moreover, the novel finding of this study is that while IGF-1 receptor-mediated Akt activation contributes to cardiac ...
Other aspects of this invention include a delivery system comprising an antibody reactive with a transferrin receptor linked to ... of an antibody-neuropharmaceutical or diagnostic agent conjugate wherein the antibody is reactive with a transferrin receptor. ... These receptors are also on the cell surface of the endothelial cells which line brain capillaries. Among the receptor types ... The ligands are those substances which usually react with these receptors (e.g. IGF 1, IGF 2 or insulin), derivatives of these ...
Type I receptors of the TGFβ pathway arose as a pairing of novel animal domains with ancient domains (type II novelties) and ... IGF, insulin-like growth factor; PTEN, phosphatase and tensin homolog; GTPase, guanosine triphosphatase; SOCS, suppressor of ... type III). The receptor in the Wnt pathway, frizzled, also arose as a type I eumetazoan novelty. Transcription factors that are ... the former being a type I novelty and the latter a type II novelty). FAK is a cytosolic component that appears as a type II ...
  • Insulin-like growth factor II receptor as a multifunctional binding protein. (
  • Lee, W. H. / Analysis of insulin-like growth factors (IGF)-I, and -II, type II IGF receptor and IGF-binding protein-2 mRNA and peptide levels in normal and nephrectomized rat kidney . (
  • While the N-terminal ( IPR000867 , IGF binding protein domain), and the C-terminal ( IPR000716 , thyroglobulin type-1 repeat) domains are conserved across vertebrate species, the mid-region is highly variable with respect to protease cleavage sites and phosphorylation and glycosylation sites. (
  • We assessed single nucleotide polymorphisms (SNPs) in the IGF-1, IGF-2, IGF-3, IGF-1 receptor (IGF1R), IGF-2 receptor (IGF2R), and IGF -binding protein 3 (IGFBP-3) genes, and their association with demographics and metabolic proteins in girls with CPP. (
  • We would like to propose an alternative interpretation, based on the main activity of PAPP-A, which is to cleave insulin-like growth factor-1 (IGF-1) from its binding protein-4, thereby increasing the accessibility of free IGF-1 to tissues. (
  • 2 PAPP-A cleaves IGF binding protein-4 and -5 in vitro 3 and may function similarly in vivo to enhance local IGF bioavailability. (
  • CREB3L3 overexpression activated gene expression levels and plasma levels of antidiabetic hormones, including fibroblast growth factor 21 and IGF-binding protein 2. (
  • Immunocytochemistry, in situ hybridization, and radioimmunoassay were employed to examine the cellular distribution of mRNAs and proteins for IGF-I, II, IGF-II/M6P receptor, IGFBP2 as well as the levels of IGF-I and II in normal and unilaterally nephrectomized (Nx) adult rat kidneys. (
  • The proliferative response of both REC and SMC to IGF-I in hyperglycemia is dependent upon the interaction between the extracellular domains of two transmembrane proteins, integrin-associated protein (IAP) and SHP substrate 1 (SHPS-1) [ 27 ]. (
  • We show that feeding-regulated hormones insulin and insulin-like growth factor 1 (IGF-1) reset circadian clocks in vivo and in vitro by induction of PERIOD proteins, and mistimed insulin signaling disrupts circadian organization of mouse behavior and clock gene expression. (
  • Additionally, we examined multiple phosphorylated proteins (i.e., protein kinase B/Akt and ErbB2/HER-2 kinase) associated with cancer development. (
  • Results show that many of these phosphorylated proteins were activated specifically in the A-ZIP/F-1 skin but not in the wild-type skin. (
  • A final important determinant of IGF activity is through a family of at least six distinct IGF-binding proteins (IGFBP) that modulate bioavailability of IGFs in the circulation. (
  • IGF-I activity is regulated by one or more of the six extracellular IGF-binding proteins (IGFBPs). (
  • Insulin-like Growth Factor Binding Proteins (IGFBP) are a group of vertebrate secreted proteins, which bind to IGF-I and IGF-II with high affinity and modulate the biological actions of IGFs. (
  • Like other binding proteins, IGFBP can prolong the half-life of IGFs via high affinity binding of the ligands. (
  • In addition to functioning as simple carrier proteins, serum IGFBPs also serve to regulate the endocrine and paracrine/autocrine actions of IGF by modulating the IGF available to bind to signalling IGF-I receptors [ PMID: 12379487 , PMID: 12379489 ]. (
  • The liver is a major source of circulating insulin-like growth factor I (IGF-I), and it also synthesizes several classes of IGF binding proteins (IGFBPs). (
  • A family of circulating IGF binding proteins (IGFBPs) are important modulators of IGF-I actions ( 15 ). (
  • We tested the association between these molecular alterations and downstream activated proteins (like phospho-protein kinase B (p-AKT), phospho-mammalian target of rapamycin (p-mTOR), p-ERK1/2, and p-p70S6K). (
  • Expression of IGF-binding proteins (IGFBPs)-1 through -6 mRNA was low throughout the growth plate compared with perichondrium and bone. (
  • IGF stands for INS like growth factors, which are proteins that have a high similarity to INS. (
  • A family of six high-affinity IGF-binding proteins. (
  • There are two proteins that mediate the effects of growth factors in beta cells, the insulin-producing cells in the pancreas: insulin receptor, a protein that mediates the action of insulin, and IGF-1 receptor, another protein that closely resembles the insulin receptor and mediates the action of insulin-like-growth factor (IGF-I), a hormone and growth factor. (
  • After IGF-I receptor activation, the heterotetrameric receptor that contains intrinsic tyrosine kinase activity phosphorylates two proteins that are important for signal transduction, IRS-1 and IRS-2 ( 9 , 10 ). (
  • IGF-binding proteins (IGFBPs) also have been shown to be important determinants of cellular responsiveness to IGF-I ( 13 ). (
  • It is transported in plasma bound to different forms of IGF-1 binding proteins. (
  • A large number of studies have been performed at in vivo and in vitro levels to study the production, effect, and receptors of insulin-like growth factors I and II (IGF-I and IGF-II), In this report, the production of IGFs and their binding proteins is described from various types of vascular cells. (
  • In summary, this review provides extensive evidence that IGF-I and IGF-II and their binding proteins can have substantial effects on the vascular cells with regard to metabolism, growth, and angiogenesis. (
  • Histone and Peroxisome Distribution in U-2 OS Cells - Nuclear histone proteins were targeted in a culture of human osteosarcoma cells with mouse anti-histone (pan) monoclonal antibodies, which were imaged with goat anti-mouse Fab fragments conjugated to the cyanine dye, Cy2 (labeling the nucleus). (
  • Growth hormone and IGF-I also influence metabolism, including how the body uses and stores carbohydrates, proteins, and fats from food. (
  • Moreover, overexpression of both IGF-IR and IR-A in breast cancer cells, leads to overexpression of hybrid IR/IGF-IR receptors (HRs) as well. (
  • Overexpression of InsR and IGF-IR has been detected in human breast cancers ( 3-5 ), and overexpression of either receptor is tumorigenic in mouse tumor models ( 6 ). (
  • IGF-I receptor (IGF-IR) overexpression has been linked to neoplastic development and it has been suggested that it has a role in regulating proliferation and differentiation even when its expression is low ( 10 ). (
  • Molecular analyses revealed that insulin-related growth factor 2 (IGF2)/MAPK signaling is elevated in the cortex of double mutants and that IGF2 overexpression in the anterior cingulate cortex is sufficient to enhance fear memory consolidation. (
  • Moreover, adeno-associated virus type 2-mediated IGF2 overexpression in the anterior cingulate cortex enhanced remote fear memory formation and the analysis of forebrain-specific double null mutants of the Insulin and IGF1 receptors revealed their essential function for memory formation. (
  • Delbono, Osvaldo 2007-02-28 00:00:00 We investigated the effects of exclusive and sustained transgenic overexpression of insulin-like growth factor (IGF)-I in the central nervous system (CNS) on the age-dependent decline in muscle strength, excitation-contraction coupling, muscle innervation and neuromuscular junction postterminal architecture. (
  • We found that (1) transgenic IGF-I overexpression in the CNS does not modify the decline in extensor digitorum longus (EDL) and soleus muscle weight with aging and (2) strength significantly decreases in transgenic (Tg) compared to wild-type mice. (
  • Our results raise questions about the timing and cell location of CNS IGF-I overexpression necessary to prevent or to ameliorate age-dependent alterations in the structure and function of skeletal muscle. (
  • Our results demonstrate that IGF-I overexpression produces persistent increases in the total number of neurons and synapses in the dentate gyrus, indicating that IGF-I promotes both neurogenesis and synaptogenesis in the developing hippocampus in vivo . (
  • We previously demonstrated that overexpression of insulin receptor isoform A (IRA) and insulin-like growth factor-I receptor (IGF-IR) confers a proliferative and migratory advantage to vascular smooth muscle cells (VSMCs) promoting plaque growth in early stages of atherosclerosis. (
  • InsR heterodimerizes with the highly homologous IGF-I receptor (IGF-IR), which also binds IGF-I and IGF-II ( 2 ). (
  • Although commonly referred to as the IGF-I receptor, it binds both IGF-I and IGF-II with high affinity. (
  • 1. A method for delivering a therapeutically effective amount of nerve growth factor across the blood brain barrier of a mammal comprising administering antibody-nerve growth factor conjugate to the mammal under conditions whereby said conjugate binds to transferrin receptors on brain capillary endothelial cells and nerve growth factor is transported across the blood brain barrier of the mammal in a pharmaceutically active form and in a therapeutically effective amount. (
  • 2. A method of claim 1 wherein the antibody portion of said conjugate comprises a monoclonal antibody which binds to transferrin receptor on brain capillary endothelial cells. (
  • 8. A method for treating a neurological disorder in a mammal comprising administering of a therapeutically effective amount of an antibody-nerve growth factor conjugate to the mammal under conditions whereby said conjugate binds to transferrin receptors on brain capillary endothelial cells and nerve growth factor is transported across the blood brain barrier in a pharmaceutically active form which thereby alleviates the neurological disorder. (
  • 11. A method for supporting the growth of cholinerigc neurons in the brain of a mammal comprising administering of an effective amount of an antibody-nerve growth factor conjugate to the mammal under conditions whereby said conjugate binds to transferrin receptors on brain capillary endothelial cells and nerve growth factor is transported across the blood brain barrier in a physiologically active form which thereby supports the growth of cholinergic neurons. (
  • The released GH then binds with the receptors present on various body organs and regulates the body composition. (
  • The type 1 IGF receptor binds both IGF-I and IGF-II with high affinity. (
  • The insulin receptor binds IGF-I with roughly 100-fold lower affinity than insulin. (
  • Insulin lispro (Humalog) is an insulin analog that differs from human insulin in amino acid sequence but binds to insulin receptors and thus functions in a manner similar to human insulin. (
  • To get insight into the signal transduction pathways connecting CXCR4 to apoptosis following gp120 binding, we used different cell lines expressing wild-type CXCR4 and a truncated form of CD4 that binds gp120 but lacks the ability to transduce signals. (
  • It also binds to specific IGF-1 tyrosine kinase receptor and the insulin receptor. (
  • 20 Adiponectin binds to two main receptors AdipoR1 and AdipoR2 and one receptor similar to the cadherin family. (
  • Insulin-like growth factor (IGF)-1 binds to the type I IGF receptor (IGF-1R), which is present on many cell types found in the plaque. (
  • The IS circuit in fruit flies is discussed as an evolutionary ancestor of its vertebrate pendant with insulin and IGF signaling merged into one pathway. (
  • To determine if administration of the potent glucocorticoid dexamethasone down-regulates SkM androgen receptor and the IGF-1 signalling pathway. (
  • The IGF pathway comprises a complex system of molecules involved in regulation of a diverse array of biological functions both normal and pathologic ( 9 ). (
  • The presence of progesterone receptor (PR) is expression of an intact oestrogen regulatory pathway of breast malignant epithelial cells and represents a parameter of cell differentiation in breast cancer. (
  • Golan and Javle suggest that the road ahead lies in the "identification and validation of biomarkers of IGF-I pathway activation in clinical samples. (
  • The binding of IGFBP to its putative receptor on the cell membrane may stimulate the signalling pathway independent of an IGF receptor, to mediate the effects of IGFBPs in certain target cell types. (
  • A simplified diagram of one intracellular signaling pathway associated with tyrosine kinase activity of the type 1 insulin-like growth factor receptor (IGFR1). (
  • Molecular changes associated with age include telomere dysfunction, oxidative stress and deranged mitochondrial metabolism, inflammation, and cellular senescence, as well as altered signaling of sirtuins, insulin/insulin-like growth factor-1 (IGF-1), and the mammalian target of rapamycin (mTOR) pathway [ 3 , 4 , 5 ]. (
  • Our data suggests that resveratrol not only suppresses cell proliferation by inhibiting IGF-1R and its downstream signaling pathways similar to that of IGF-1R siRNA but also enhances apoptosis via activation of the p53 pathway. (
  • Inhibitors of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway can overcome endocrine resistance in estrogen receptor (ER) α-positive breast cancer, but companion diagnostics indicating PI3K/AKT/mTOR activation and consequently endocrine resistance are lacking. (
  • daf-2 , a key gene in the genetic pathway that mediates this endocrine signaling, encodes an insulin receptor family member. (
  • Activation of the αVβ3 receptor results in an interaction with the IGF-I signal transduction pathway, which modulates SMCs responsiveness to IGF-I. (
  • In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway. (
  • Leptin induces cell proliferation of endometrial cancer cells by activation of cyclooxygenase-2 through the JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathway. (
  • 3,4 Even mild damage, such as brief ischemia, would activate this pathway, 2 thus explaining the higher sensitivity of PAPP-A compared with cardiac troponins as predictors of outcome. (
  • Thymidine incorporation in hepatocytes in the presence of EGF and IGF-II was inhibited by soluble receptor (50% inhibition at 212 +/- 45 ng/ml). (
  • Although soluble receptor blocked IGF-II binding to hepatocytes, inhibition of EGF-stimulated DNA synthesis was not due to inhibition of EGF binding or uptake by the cell. (
  • Inhibition of InsR and IGF-IR with the dual tyrosine kinase inhibitor OSI-906 prevented the emergence of hormone-independent cells and tumors in vivo , inhibited parental and LTED cell growth and PI3K/AKT signaling, and suppressed growth of established MCF-7 xenografts in ovariectomized mice, whereas treatment with the neutralizing IGF-IR monoclonal antibody MAB391 was ineffective. (
  • Selective estrogen receptor degraders (SERD), such as fulvestrant, induce effective ER signaling inhibition, although clinical studies with fulvestrant report insufficient blockade of ER signaling, possibly due to suboptimal pharmaceutical properties. (
  • 5] When tumors are carefully examined, many cancers have substantial expression of insulin receptor,[6] and experimental models have shown that inhibition of insulin receptor and IGF-1R together might improve tumor inhibition. (
  • Inhibition IFG-1 receptor reduces pancreatic cancer growth and angiogenesis. (
  • Inhibition of IGF-1R signaling with AMG 479 provides a potential mechanism for inhibiting tumor growth and survival. (
  • By the inhibition of PKC-α/CaMKII activity, we found that IGF-II and Leu27IGF-II-induced cell hypertrophy and upregulation of ANP and BNP were significantly suppressed. (
  • In vitro experiments showed that IGF-IR inhibition by picropodophyllin induced apoptosis in VSMCs. (
  • As a consequence of the acceleration in IAP cleavage, the compounds were shown to inhibit IGF-I-stimulated phosphorylation of key signaling molecules including Shc and ERK1/2, and this in turn was associated with a decrease in IGF-I-stimulated cell proliferation. (
  • 95% reduction in IR expression specifically in skeletal muscle and a parallel decrease in insulin-stimulated IR and insulin receptor substrate-1 phosphorylation. (
  • Wnt3a-dependent phosphorylation of Akt was blocked in cells deficient in both the insulin receptor (IR) and the insulin-like growth factor 1 (IGF-1) receptor (IGF1R). (
  • however, loss of LRP5 had no effect on IGF-1-dependent phosphorylation of these targets. (
  • Binding of IGF to the receptor initiates a cascade of downstream events, including the activation of tyrosine kinase, phosphorylation of the insulin-receptor substrate (IRS)-1, and subsequent activation of either phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin or RAF-mitogen-activated protein kinase systems (reviewed in refs. (
  • Molecular and biochemical analyses revealed elevated insulin-related growth factor 2 (IGF2) signaling and increased phosphorylation of MAPK and S6 in the Cx but not the Hi of S1/2 −/− mice. (
  • Therefore blocking occupancy of αVβ3 inhibited multiple target cell actions of IGF-I. To determine whether blocking αVβ3 occupancy could alter IGF-I receptor-mediated signal transduction, the ability of IGF-I to stimulate phosphorylation of insulin receptor substrate-1 (IRS-1) was analyzed. (
  • A 10-min exposure to 100 ng/ml of IGF-I resulted in a substantial increase in phosphorylated IRS-1, and echistatin (10 −7 M) blocked the IGF-I-induced IRS-1 phosphorylation response. (
  • Echistatin (10 −7 M) significantly reduced IGF-I-stimulated tyrosine phosphorylation of the IGF-I receptor β subunit. (
  • Several lines of experimental evidence have shown that phosphorylation of IRS-1 is required for certain IGF-I-mediated biologic responses ( 11 ). (
  • Using Leu27IGF-II, an analog of IGF-II which interacts selectively with the IGF2R, to specifically activate IGF2R signaling cascades, we found that binding of Leu27IGF-II to IGF2R led to an increase in the phosphorylation of protein Kinase II (PKC)-α and calcium/calmodulin-dependent protein kinase 11 (CaMKII) in a Gαq-dependent manner. (
  • The cation-independent mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R or IGF2R) traffics IGF2 and M6P ligands between pre-lysosomal and extra-cellular compartments. (
  • The function of the fifteen homologous extra-cellular domains of the cation-independent mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R or IGF2R) include the binding, trafficking and extra-cellular internalisation of ligands, such as Insulin-like growth factor 2 (IGF2), mannose 6-phosphate (M6P) modified lysosomal proteases and plasminogen 1 . (
  • Our recent reports indicate that pharmacological aryl hydrocarbon receptor (AHR) ligands inhibit breast cancer cell responses to IGFs, suggesting that targeting AHR may have benefit in cancers whose proliferation and survival are dependent on insulin/IGF signaling. (
  • Officially, the U.S. Food and Drug Administration (FDA) refers to these as "insulin receptor ligands", although they are more commonly referred to as insulin analogs. (
  • Ligands targeting the σ receptor are in clinical trials for treatment of Alzheimer's disease, ischemic str. (
  • In contrast, exposure of SMCs to vitronectin (1.0 μg/cm 2 ) or thrombospondin (0.25 μg/cm 2 ), two known ligands for αVβ3, resulted in enhancement of the IGF-I-stimulated IRS-1 response. (
  • Fish are the first vertebrate group which has a complete system of ligands and receptors for the insulin / IGF family. (
  • One of these mechanisms is the aberrant expression of insulin receptor (IR) isoform A (IR-A), which is a high affinity receptor for both insulin and IGF-II, in breast cancer cells. (
  • It has a high affinity for the type I IGF receptor, a membrane bound tyrosine kinase with similar organisation to the insulin receptor. (
  • The C terminus is also required for high affinity IGF binding, as well as for binding to the extracellular matrix [ PMID: 9725901 ] and for nuclear translocation [ PMID: 7519375 , PMID: 9660801 ] of IGFBP-3 and -5. (
  • It is well recognized that the epithelial breast cancer cells commonly overexpress the IGF-I receptor while IGF-II is expressed by the tumor stroma. (
  • Studies have implicated InsR in transformation and breast cancer mitogenesis, and hyperinsulinemia can accelerate mammary tumor progression in a mouse model of type II diabetes ( 9 ). (
  • CAP1 was associated with poor tumor characteristics with higher CAP1 expression among estrogen receptor (ER)-negative tumors, relative to ER-positive tumors ( P = 0.025), and higher histological grades ( P = 0.016). (
  • In two cancer models, the classic two-stage skin carcinogenesis protocol and the C3(1)/T-Ag transgenic mouse mammary tumor model, A-ZIP/F-1 mice displayed higher tumor incidence, tumor multiplicity, and decreased tumor latency than wild-type mice. (
  • In two different cancer models, we found that A-ZIP/F-1 mice are more prone to develop tumors as indicated by their higher tumor incidence, tumor multiplicity, and decreased tumor latency than wild-type mice. (
  • This is attributed to downstream events such as loss of tumor-suppressor gene PTEN that may augment signals from IGF-IR ( 9 ). (
  • Tumor environments usually abound in protesases that can digest IGFBPs to release free IGF resulting in increased IGF signaling. (
  • Similarly, in vivo treatment with SAR439859 demonstrated significant tumor regression in ER+ breast cancer models, including MCF7- ESR1 wild-type and mutant-Y537S mouse tumors, and HCI013, a patient-derived tamoxifen-resistant xenograft tumor. (
  • Conatumumab is an investigational fully human monoclonal antibody agonist that targets death receptor 5 (DR-5) and induces apoptosis - programmed cell death - in sensitive tumor cells. (
  • Resveratrol treatment induced apoptosis by activating tumor suppressor p53 protein, whereas IGF-1R siRNA treatment did not affect apoptosis. (
  • In view to the fact that the IGF-IR has mitogenic, pro-invasive and anti-apoptotic effects and mediates resistance to a variety of anti-cancer therapies, breast cancer is expected to be a candidate to therapeutic approaches aimed to inhibit the IGF-IR. (
  • IGFBPs bind to IGF-I, and most inhibit binding between IGF-I and the IGF-I receptor (IGFIR) (1,2). (
  • Responses to IGFBP-5 are biphasic in that, when a low concentration of this material is associated with extracellular matrix, it can act to enhance IGF-I actions, whereas when a high concentration of intact, nonproteolytically cleaved protein is present in interstitial fluids, it acts to inhibit IGF-I binding to receptors and inhibits IGF-I actions ( 18 , 19 ). (
  • Upon binding to IGF-II, both IR-A and HRs may activate unique signaling patterns, which predominantly mediate proliferative effects. (
  • Thus, we aimed to explore the effects of chronic, continuous, subcutaneous (s.c.) exposure to Ex-4 in brain cortical GLP-1/insulin/insulin-like growth factor-1 (IGF-1) signaling, and in autophagic and cell death mechanisms in middle-aged (8 months old), male T2D Goto-Kakizaki (GK) rats. (
  • GLP-1, insulin, and IGF-1, their downstream signaling and autophagic markers were evaluated by specific ELISA kits and Western blotting. (
  • Ex-4 enhanced their brain cortical GLP-1 and IGF-1 levels, and subsequent signaling pathways. (
  • Activation of the intrinsic kinase activity of the IGF-I receptor (IGF-IR) is required to trigger downstream signaling events that lead to cellular proliferation. (
  • Insulin and IGF-1 receptor signaling is sufficient to determine essential circadian parameters, principally via increased PERIOD protein synthesis. (
  • Signaling by Wnt glycoproteins, which are important in development, is mediated by Frizzled receptors and the co-receptors low-density lipoprotein receptor-related protein 5 (LRP5) and LRP6. (
  • Together, these data suggest that the Wnt and insulin signaling pathways exhibit crosstalk in preadipocytes at the level of the Wnt co-receptor LRP5, which the authors suggest may act as a co-receptor for IR signaling. (
  • Both insulin and Wnt signaling in preadipocytes depend on the Wnt co-receptor LRP5. (
  • Furthermore, the upstream signaling and the downstream targets involved in cardiac autophagy regulation during obesity and type 2 diabetes mellitus (T2DM) are not fully elucidated. (
  • The findings are of significant importance as they demonstrate for the first time the contribution of IGF-1 receptors (IGF-1R) and Akt signaling in cardiac hypertrophy but not in cardiac autophagy regulation in obesity and T2DM. (
  • however, studies indicate that the risk of common cancers, such as colon ( 1 ), breast ( 2 ), and prostate ( 3 ), is increased in individuals who have higher circulating levels of IGF-I. Increased IGF-I signaling stimulates proliferation and promotes metastasis of cancer cells and therefore represents a promising target for treatment as well as prevention of cancer ( 4 - 8 ). (
  • High concentrations of IGF may stimulate insulin signaling through this receptor. (
  • Binding of human immunodeficiency virus type 1 gp120 to CXCR4 induces mitochondrial transmembrane depolarization and cytochrome c-mediated apoptosis independently of Fas signaling. (
  • Impaired fear memory formation in aged S1/2 −/− mice indicates that elevated IGF2 signaling in the long term, however, has a negative impact on cognitive processing. (
  • Signaling through IGF-1R plays an important role in the regulation of cell growth and survival. (
  • Taken together these data suggest mechanistic links between impaired insulin-and IGF-1-signaling in diabetes and cognitive dysfunction. (
  • Hyperglycemia, perturbed function of insulin, and IGF-1 signaling have been proposed as pathogenetic factors contributing to Alzheimer's disease ( 8 - 10 ), suggesting that diabetes and Alzheimer's disease may share common underlying causative mechanisms. (
  • Our findings shed light on the complex role of insulin signaling in fine-tuning brain functions, and provide further experimental evidence in support of the recently elaborated theory of type 3 diabetes. (
  • Biased signaling agonist of Dopamine D3 receptor induces receptor internalization independent of β-Arrestin recruitment. (
  • Exposure of G protein-coupled receptors (GPCRs) to agonists can desensitize receptor signaling and lead to drug tolerance, whereas, inverse agonists may sensitize signaling. (
  • Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways. (
  • Treatment with resveratrol suppressed IGF-1R protein levels and concurrently attenuated the downstream Akt/Wnt signaling pathways that play a critical role in cell proliferation. (
  • Targeted suppression of IGF-1R using IGF-1R siRNA also affected these signaling pathways in a similar manner. (
  • CONCLUSIONS: For the first time, we report that resveratrol suppresses colon cancer cell proliferation and elevates apoptosis even in the presence of IGF-1 via suppression of IGF-1R/Akt/Wnt signaling pathways and activation of p53, suggesting its potential role as a chemotherapeutic agent. (
  • Decreases in DAF-2 signaling induce metabolic and developmental changes, as in mammalian metabolic control by the insulin receptor. (
  • Decreased DAF-2 signaling also causes an increase in life-span. (
  • These new studies suggest that the central nervous system is capable of adapting to the demands of a high-energy Western diet, coupled with ample exercise, by increasing insulin like growth factor 1 (IGF-1) signaling and the expression of silent mating type information regulation 2 homolog (SIRT1), peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α), and free radical scavengers. (
  • The present study investigated the effects of a functional deficit in insulin-like growth factor-I signaling via chronic intravenous administration of insulin-like growth factor-I (IGF-I) receptor antisense in the conscious spontaneously hypertensive rat cardiovascular system. (
  • IGF-1R signaling has been shown to play a critical role in the survival of cancer cells. (
  • We hypothesized that after binding with IGF-II, IGF2R may trigger intracellular signaling cascades involved in the progression of pathologically cardiac hypertrophy. (
  • Attenuation of daf-2 insulin-like or daf-7 TGFβ-like signaling pathways cause developmental arrest at the stress resistant and long-lived dauer stage. (
  • Thus, daf-9 may integrate outputs from daf-2 and daf-7 signaling pathways to relay neuroendocrine signals through synthesis of a lipophilic hormone. (
  • In contrast to the detailed knowledge of the DAF-2 and DAF-7 signaling cascades, the mechanism by which these pathways are integrated remains largely unknown. (
  • Based on its action downstream of daf-2 and daf-7 in the genetic epistasis analysis, daf-9 expression or activity may in turn be regulated by the upstream daf-2 and daf-7 signaling pathways. (
  • Tamoxifen, an endocrine therapy drug used to treat breast cancer, is designed to interrupt estrogen signaling by blocking the estrogen receptor (ER). (
  • The binding of growth hormone triggers signaling via the intracellular region of the receptor that stimulates the growth and division of cells. (
  • This signaling also leads to the production, primarily by liver cells, of another important growth-promoting hormone called insulin-like growth factor I (IGF-I). (
  • We review the molecular pathophysiology of type 2 5α-reductase, AR coactivators, the paracrine factors deregulated in dermal papillae (such as TGF-β, IGF 1, WNTs and DKK-1) and the crosstalk between AR and Wnt signaling in order to shed some light on new promising treatments. (
  • In this study we have examined the relationship between IGF-II mRNA expression and ER, PR content in 75 breast cancer. (
  • Our data indicate that in breast cancer IGF-II mRNA is generally expressed by stromal cells and ER and PR by ephitelial cancer cells, and that IGF-II mRNA expression is strongly related with both percentage and staining intensity of PR+ epithelial cancer cells. (
  • We also measured class 1 and class 2 IGF-I mRNAs and GH receptor mRNA expression in these cell populations to determine whether these cells represent potential target cells for IGF-I. (
  • We therefore studied the spatial and temporal patterns of mRNA expression of the GH-IGF system in the rat proximal tibial growth plate quantitatively. (
  • Estrogen receptor α (ER)-positive breast cancers adapt to hormone deprivation and become resistant to antiestrogens. (
  • Two-thirds of breast cancers express estrogen receptor α (ER) and/or progesterone receptor, biomarkers indicative of hormone dependence ( 10 ). (
  • Using RNA interference (RNAi) screening and pharmacologic inhibitors of InsR and IGF-IR, we discovered InsR and IGF-IR are required for hormone-independent breast cancer cell growth, thus providing a targetable mechanism for breast cancers that escape estrogen deprivation. (
  • Primary treatment for estrogen receptor-positive (ER+) breast cancer is endocrine therapy. (
  • The first two targeted therapies used in breast cancer (targeting the estrogen receptor [ER] and HER2) both have biomarkers to indicate the likelihood of response. (
  • 2 Similarly, women who undergo estrogen replacement without progesterone have an increased risk of endometrial cancer. (
  • Available agents for postmenopausal patients include steroidal (exemestane) and non-steroidal (anastrozole and letrozole) aromatase inhibitors (AIs), selective estrogen receptor modulators (tamoxifen or toremifene), and the estrogen receptor (ER) down-regulator fulvestrant. (
  • The mouse insulin-like growth factor type 2 receptor (Igf2r) is imprinted and expressed exclusively from the maternally inherited chromosome. (
  • Methylation of region 2 may mark the maternal Igf2r locus in a manner that could act as an imprinting signal. (
  • 80%) observed in homozygotes ( Igf2r I1565A/I1565A ) suggested that wild-type paternal allele expression attenuates the heterozygote phenotype. (
  • The structural basis of the binding interaction of IGF2 and domain 11 of IGF2R has been determined at atomic resolution, including a mechanism to account for structural co-evolution of IGF2 binding to IGF2R in relation to genomic imprinting 2 . (
  • Moreover, it also suggested that the evolved and specific IGF2 binding domain of IGF2R was also functionally independent of the other domains of the receptor. (
  • The IGF2R has also been associated with development of cancer because loss of IGF2R results in increased IGF2-initiated IGF-IR activation (ref. 9 and references therein). (
  • The role played by IGF-II in signal transduction through the IGF-II/ mannose-6-phosphate receptor (IGF2R) in heart tissue has been poorly understood. (
  • In our previous studies, we detected an increased expression of IGF-II and IGF2R in cardiomyocytes that had undergone pathological hypertrophy. (
  • Genotype data analyzed with contingency tables suggested the strongest association with insulin-like growth factor 2 receptor (IGF2R) SNPs. (
  • The mitogenic actions of insulin are mediated by the insulin receptor (InsR) tyrosine kinase ( 2 ). (
  • Low circulating levels of IGFBPs favor an increased IGF mitogenic activity. (
  • 9 Both lispro and aspart have low mitogenic potency despite the elevated IGF-1 receptor affinity of lispro, indicating that a minor increase in IGF-1 affinity is not a sufficient stimulus to provide a mitogenic stimulus to a cell line. (
  • Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activities in cultured cancer cells. (
  • Thus, in the vasculature, IGF-I has both pressor-inducing (VSMC mitogenic effect) and depressor effects, and both are altered in hypertensive models, whereas the expression of both the ligand and its receptor may increase in such circumstances. (
  • Chronically increased ciliary neurotrophic factor and fibroblast growth factor-2 expression after spinal contusion in rats. (
  • RESULTS- Neuronal loss occurred in both models, significantly more so in type 2 diabetic BBZDR/Wor rats compared with type 1 diabetic BB/Wor rats and was associated with a ninefold increase of dystrophic neurites. (
  • APP, β-secretase, β-amyloid, and CTF were significantly increased in type 2 diabetic rats, as was phospho-τ. (
  • In type 1 diabetic BB/Wor rats, progressively impaired cognitive function is associated with suppressed insulin and IGF-1 actions and neuronal apoptosis in hippocampus ( 6 ), changes that are significantly prevented by insulinomimetic C-peptide ( 7 ). (
  • For a better understanding of the insulin effect on the central nervous system, we performed microarray-based global gene expression profiling in the hippocampus, striatum and prefrontal cortex of streptozotocin-induced and spontaneously diabetic Goto-Kakizaki rats as model animals for type 1 and type 2 diabetes, respectively. (
  • With increasing age (3-, 6-, 9-, and 12-week castrated rats), IGF-I mRNA levels increased in the proliferative zone (PZ) but remained at least tenfold lower than levels in perichondrium and bone. (
  • We recently found that IGF-IR antisense reduced the pressor response to angiotensin II and decreased AT 1 R expression in normotensive rats ( Nguyen and White, 2005 ). (
  • In normotensive rats, IGF-I causes nitric oxide-mediated vasodilation, an effect that is in opposition to the increase in angiotensin receptor expression and function mediated by IGF-I. Given that in hypertensive rats the vasodilator effects of IGF-I are reduced compared with normotensive controls, the effects of IGF-I on angiotensin receptor expression and function may be of greater functional significance in these animals. (
  • Insulin-like growth factor-II/mannose 6-P (IGF- II/M6P) receptor is released from cultured cells and tissues in a soluble form that retains its affinity for IGF-II. (
  • Pharmacodynamically, lispro and aspart bind as well to insulin receptors as does human insulin, but lispro has a slightly elevated affinity for the Insulin-like Growth Factor 1 (IGF-1) receptor (156 ± 16% for lispro vs. 81 ± 9% for aspart). (
  • The IGFBP family has six distinct subgroups, IGFBP-1 through 6, based on conservation of gene (intron-exon) organisation, structural similarity, and binding affinity for IGFs. (
  • Insulin-like growth factor-I (IGF-I) stimulates SMC migration and proliferation and has therefore been implicated in the lesion progression [ 1 - 3 ]. (
  • Many neoplastic cells produce IGF-I, which regulates a number of cellular processes, including energy metabolism, proliferation, and cell survival (3,4). (
  • IGF-I and IGFIR are frequently expressed by cancer cells and may contribute to the proliferation and viability of a number of cancer types (1,2). (
  • Resveratrol (trans-3, 4', 5,-trihydroxystilbene), a stilbenoid found in the skin of red grapes and peanuts suppresses many types of cancers by regulating cell proliferation and apoptosis through a variety of mechanisms, however, resveratrol effects on obesity-promoted colon cancer are not clearly established. (
  • A potential explanation for these associations is that insulin-like growth factor 1 (IGF-1) is positively correlated with both birth weight and head circumference and may also stimulate the proliferation of malignant cells ( 11 ). (
  • 1 , 2 Lending support to this hypothesis, during the follicular phase of the menstrual cycle, progesterone levels are low, estradiol levels are at normal premenopausal levels, and increased endometrial proliferation is observed. (
  • In this project we have investigated the role of Axl receptor inschwannoma pathological proliferation, cell-matrix adhesion and survival. (
  • In these studies we have demonstrated that IGF1/2 and IGFBP-1 arereleased from schwannoma cells and IGF-I receptor overexpressed leading toincreased schwannoma proliferation and cell-matrix adhesion. (
  • G α 13 and v-Src induces the transformation of wild type and Igf1r null MEFs ( 4 , 5 ). (
  • Ciliary neurotrophic factor induces expression of the IGF type I receptor and FGF receptor 1 mRNAs in adult rat brain oligodendrocytes. (
  • Thus, insulin resistance in muscle contributes to the altered fat metabolism associated with type 2 diabetes, but tissues other than muscle appear to be more involved in insulin-regulated glucose disposal than was previously recognized. (
  • RESEARCH DESIGN AND METHODS We identified 425 individuals, divided into seven categories according to carbohydrate metabolism status (normal glucose tolerance [NGT], impaired fasting glucose, impaired glucose tolerance [IGT], and newly diagnosed type 2 diabetes) and diabetes duration (0-9, 10-19, and ≥20 years). (
  • Learn all about type 1 and type 2 diabetes and the differences between the two conditions in our article about the diabetes mellitus metabolism disorder. (
  • The central hypothesis being tested by Dr. Scarisbrick's research team is that diet and exercise induced changes in critical regulators of metabolism, such as IGF-1 SIRT1, PGC-1α and free radical scavengers regulate the capacity of the nervous system to generate and repair myelin. (
  • Changes in metabolism caused by insensitivity to growth hormone and the resulting shortage of IGF-I cause many of the other features of the condition, including obesity. (
  • however, under certain conditions, several of the IGFBPs apparently are capable of enhancing IGF action by facilitating IGF delivery to target receptors. (
  • The fact that IGFBPs have a variety of IGF-independent functions is currently a subject of intense investigation ( 11 - 13 ). (
  • Some IGFBPs may increase cell responses to IGF-I. Binding of IGF-I to IGFIR activates the Akt, JNK, and Erk pathways (2). (
  • Furthermore, IGFBPs can function as growth modulators independent of IGFs. (
  • IGFBP-1 and -2, but not other IGFBPs, contain a C-terminal Arg-Gly-Asp integrin-binding motif. (
  • Synthesis of IGF-I and IGFBPs is regulated by hormones, growth factors, and cytokines. (
  • To gain insight into cellular regulatory mechanisms that determine hepatic synthesis of IGF-I and IGFBPs and to identify potential target cells for IGF-I within the liver, we studied the cellular sites of synthesis of IGF-I, IGF receptor, growth hormone (GH) receptor, and IGFBPs in freshly isolated rat hepatocytes, endothelial cells, and Kupffer cells. (
  • Cell-specific expression of distinct IGFBPs in the liver provides the potential for cell-specific regulation of hepatic and endocrine actions of IGF-I. (
  • IGF-I also circulates bound to the other IGFBPs, but their physiological significance is less well established. (
  • The IGFBPs may act to control transport of IGF-I from the circulation to specific tissues, to provide for cell- and tissue-specific localization of IGF-I, and to modulate the interaction between IGF-I and its receptor ( 15 ). (
  • In addition, the decrease in growth velocity that occurs with age may be caused, in part, by decreasing expression of IGF-II and increasing expression of type 2 IGF receptor and multiple IGFBPs. (
  • SMCs have been shown to synthesize and secrete three forms of IGFBPs, including IGFBP-2, -4, and -5 ( 14 ). (
  • To test the possibility that soluble receptor can therefore modulate the activity of IGF-II, we determined the effect of purified soluble receptor on DNA synthesis in cultured rat hepatocytes stimulated with epidermal growth factor (EGF) (5 ng/ml) and IGF-II (200 ng/ml). (
  • Immunohistochemistry was performed for human epidermal growth factor receptor 2 (HER2), phosphatase and tensin homolog (PTEN), and insulin-like growth factor 1 receptor (IGF-1R). (
  • The standard of care for patients with hormone receptor positive, human epidermal growth factor receptor type 2 negative advanced breast cancer is endocrine therapy. (
  • Herein, we will review and discuss current issues in the endocrine treatment of postmenopausal patients with hormone receptor positive, human epidermal growth factor receptor type 2 negative advanced breast cancer. (
  • Postmenopausal patients with hormone receptor positive (HR+), human epidermal growth factor receptor type 2 negative (HER2-) tumors represent the majority of patients with advanced breast cancer (ABC). (
  • Apoptosis of CD4(+) T lymphocytes, induced by contact between human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120) and its receptors, could contribute to the cell depletion observed in HIV-infected individuals. (
  • However, the role of insulin receptor (IR) isoforms, IGF-IR or insulin-like growth factor-II receptor (IGF-IIR) in VSMCs apoptosis during advanced atherosclerosis remains unclear. (
  • Apoptosis induced by thapsigargin was lower in IR −/− VSMCs expressing higher IGF-IR levels as compared to IRLoxP +/+ VSMCs. (
  • In advanced human atherosclerosis, a reduction of IRA/IRB ratio, decreased IGF-IR expression, or increased IGF-IIR may contribute to VSMCs apoptosis, promoting plaque instability and increasing the risk of plaque rupture and its clinical consequences. (
  • These data suggest that renal IGF-I and IGFBP2 are synthesized at upstream sites along the nephron and then transported downstream for interaction with IGF receptors. (
  • The authors clearly outline the endocrine effects of blocking IGF-1R with monoclonal antibodies: elevated growth hormone levels and increased levels of both glucose and insulin. (
  • AMG 479 is an investigational fully human monoclonal antibody that targets type 1 insulin-like growth factor receptor (IGF-1R). (
  • AMG 479 is a fully human monoclonal antibody (IgG1) against the insulin-like growth factor receptor-1 (IGF-1R). (
  • Rosenfeld, RG & Pham, H 1987, ' Production of monoclonal antibodies to the rat insulin-like growth factor II (IGF-II) receptor ', Biochemical and Biophysical Research Communications , vol. 146, no. 2, pp. 717-724. (
  • U-2 OS Human Osteosarcoma Cells with the Cyanines Cy2 and Cy3, as well as Alexa Fluor 350 - Histones present in the nuclei of cancerous bone cells (U-2 OS line) were immunofluorescently labeled with primary anti-histone mouse monoclonal antibodies followed by goat anti-mouse Fab heavy and light chain fragments conjugated to Cy3. (
  • Metabolic syndrome (MetS) represents a cluster of metabolically related symptoms such as obesity, hypertension, dyslipidemia, and carbohydrate intolerance, and significantly increases type 2 diabetes mellitus risk. (
  • Comorbid depression is common in patients with type 2 diabetes mellitus and is associated with greater mortality risk and a higher incidence of diabetic complications and decreased quality of life. (
  • The present data underline the importance of diagnosis and treatment of comorbid depression in patients with type 2 diabetes mellitus with milnacipran. (
  • This study is to systematically investigate the relationship between metformin and risk of pancreatic cancer in patients with type 2 diabetes mellitus. (
  • Cohort or case control studies of metformin and risk of pancreatic cancer in patients with type 2 diabetes mellitus were included. (
  • In addition, epidemiological studies have shown that diabetes, especially non-insulin-dependent diabetes mellitus (Type 2 Diabetes, T2DM) can increase the risk of pancreatic cancer [ 2 , 8 , 9 ]. (
  • It may be important in the pathophysiological processes underlying chronic disease, including type 2 diabetes mellitus, coronary heart disease, cancer and Alzheimer's. (
  • When you use one through the production of IGF-1 also insulin therapy and type 2 diabetes mellitus with an increased HGH lowest price risk of developing CRC was found. (
  • ROS Acts as a Double-Edged Sword in the Pathogenesis of Type 2 Diabetes Mellitus: Is Nrf2 a Potential Target for the Treatment? (
  • Metformin (1,1-dimethylbiguanide hydrochloride) is a biguanide commonly used to treat type 2 diabetes mellitus. (
  • We conclude that therapeutic targeting of both InsR and IGF-IR should be more effective than targeting IGF-IR alone in abrogating resistance to endocrine therapy in breast cancer. (
  • Most circulating endocrine-acting insulin-like growth factor I (IGF-I) is produced by hepatocytes, and paracrine- or autocrine-acting IGF-I is produced by defined cell types within specific tissues (1,2). (
  • These findings indicate that SAR439859 may provide therapeutic benefit to patients with ER+ breast cancer, including those who have resistance to endocrine therapy with both wild-type and mutant ER. (
  • In the future, poly-endocrine therapy and combination therapies with biological agents might become valuable options for the first line treatment of hormone receptor-positive advanced breast cancer. (
  • 2010). The structure and function of dIlps and the putative precursor protein are similar to human insulin and insulin-like growth factor (IGF) peptides or pre-pro-insulin ,respectively, implying an analogous organization of the final secreted peptide (Brogiolo et al. (
  • The somatomedins, IGFs, comprise a family of peptides that play important roles in mammalian growth and development. (
  • IGF-I is distributed in several tissues and its expression is triggered by an assortment of factors, which is a hallmark of regulatory peptides. (
  • Review work on IGFs and various related peptides are available but information on IGF-I, its regulatory effects on growth, celldivision, adaptation, behavior, gonadal maturation and gamatogenesis etc are fragmentary. (
  • Evolutionary studies on IGFs , related peptides and their receptors have been carried out by many workers [115,78,177]. (
  • Role of IGFs and related peptides in gonadal development in fishes has been studied by Melamed et al [107] and Patino et al [125]. (
  • Reviews in relation to the regulation of growth by IGF-I and related peptides [37,135,114] are available in the literatures. (
  • IGF-I has independent evolutionary history than that of the related peptides as insulin. (
  • This discovery implied that ESE selection lead to acquisition of IGF2 binding to one of its fifteen domains 2 . (
  • New advances in the molecular basis of anti-IGF1R blocking antibodies reveal they are biased agonists and promote the binding of IGF1 to integrin β3 receptors in some cancer cells. (
  • Liver specific Igf1 knockout mice have lower levels of circulating IGF1 (by ~75%) than wild type mice ( 7 , 8 ). (
  • Specifically, breast tumors grow slower in IGF1 deficient mice than wild type mice ( 9 ). (
  • In contrast, Laron-type dwarfism is associated with low IGF1 levels and reduced cancer risk ( 12 ). (
  • Lyophilized IGF1 although stable at room temperature for 3 weeks, should be stored desiccated below -18°C. Upon reconstitution IGF1 should be stored at 4°C between 2-7 days and for future use below -18°C. (
  • Type 2 diabetes (T2D) is a modern socioeconomic burden, mostly due to its long-term complications affecting nearly all tissues. (
  • While growth of many cancers is influenced by IGF secreted in distant tissues, there is evidence that in some cancers, IGFs are locally produced. (
  • This receptor has been identified in essentially all tissues except liver, and virtually all of the biological activities of the IGFs result from binding to the type 1 receptor. (
  • insulin-like growth factor I (IGF-I) is synthesized in most if not all tissues, but the liver appears to be a major source of circulating IGF-I ( 17 , 19 ). (
  • IGF-I mRNA abundance is 40- to 100-fold higher in liver than in nonhepatic tissues ( 20 ). (
  • Furthermore, constitutive expression of daf-9 in the hypodermis suppresses dauer arrest of daf-7 mutant animals and inhibits dauer remodelling of some tissues in daf-2 mutant animals. (
  • 2 Several lines of evidence indicate that PAPP-A is induced in response to, and within, damaged tissues, as a promoter of repair, in virtue of its IGF-1-dependent actions on vasculogenesis, vasodilation, cell preconditioning, cell survival, and insulin-sensitivity. (
  • The latter scenario of an autocrine or a paracrine dependence on IGF may turn a cancer to be more aggressive. (
  • This suggests that both IGFs maybe involved in paracrine action on multiple cell types throughout development with each IGF having its own spectrum of targets. (
  • Insulin-like growth factor-I receptor (IGF-IR) antisense, but not full mismatch treatment, decreased IGF-IR expression in both conductance and resistance blood vessels. (
  • Finally, an insulin/IGF-I gene expression signature predicted recurrence-free survival in patients with ER + breast cancer treated with the antiestrogen tamoxifen. (
  • Adipokine receptor expression was explored among breast cancer cell lines ( n = 47) and primary breast tumors ( n = 1,881), where associations with survival outcomes were investigated. (
  • In addition, our analysis in vitro using C 2 C 12 myotubes shows that Ang-(1-7), through a mechanism dependent on Mas, prevents the decrease in the levels of MHC and the increase in the expression of the atrogin-1 and MuRF-1, both induced by AngII. (
  • Relative expression of SkM androgen receptor was similar in male (1·63 ± 0·37) vs. female (1·57 ± 0·30) subjects, despite the significant difference in plasma testosterone levels. (
  • Plasma IGF-1 and SkM expression of IGF-1 and IGF-1 receptor were also similar between males and females. (
  • Following dexamethasone, there was a significant down-regulation of SkM androgen receptor (1·60 ± 0·23 vs. 1·11 ± 0·16, P 0·05) and IGF-1 (1·72 ± 0·29 vs. 1·06 ± 0·14, P 0·05) mRNA, but no change in expression of the IGF-1 receptor. (
  • IGF-II mRNA was scored semi-quantitatively: 2.6% breast tumour specimen expressed no IGF-II mRNA, 46.7% had low levels of expression (IGF-II) and 50.7% had moderate or high IGF-II mRNA content(IGF-II+). (
  • To this end, recent reports have identified gene expression[2, 3] and an integrated genomic classifier that are associated with response to IGF-1R inhibitors. (
  • Her lab found that daf-2 affects lifespan through a second gene, known as daf-16, whose function was known to control the expression of other genes. (
  • Changes in the cerebral gene expression profiles seemed to be specific for the type 2 diabetic model, as no such alterations were found in streptozotocin-treated animals. (
  • In the present study, we compared the levels of expression of type 1 IGF receptor mRNA in RNA extracted from whole adult rat liver and from freshly isolated hepatocytes, Kupffer cells, and endothelial cells prepared from adult liver. (
  • To test this idea, D'Angelo and colleagues used RNA interference (RNAi) to knock down expression of various nucleoporins in wild-type worms and daf-2 worms (these have longer life spans due to an insulin/IGF-1 receptor mutation). (
  • Previous studies of the GH-IGF system gene expression in growth plate using immunohistochemistry and in situ hybridization have yielded conflicting results. (
  • These results suggest that although the proliferative and vasodilator effects of IGF-I are impaired in SHR, the effects on angiotensin receptor expression remain profound. (
  • In VSMC, angiotensin II has been shown to potentiate IGF-I and IGF-IR expression, and this potentiation has been found to be important in the vascular growth-promoting effects of angiotensin II ( Delafontaine and Lou, 1993 ). (
  • We therefore investigated the impact of IGF-IR knockdown by IGF-IR AS on angiotensin receptor expression, resting blood pressure, and responses to noradrenaline and angiotensin II in a systolic hypertension model, the spontaneously hypertensive rat. (
  • In our study of H9c2 cardiornyoblast cell cultures, we used the rhodamine phalloidin staining to measure the cell hypertrophy and western blot to measure tho expression of cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cells treated with IGF-II. (
  • GFP expression in the hypodermis is absolutely dependent on daf-12 , the nuclear receptor that is negatively regulated by daf-9 gene activity, suggesting feedback control between daf-9 and daf-12 in this tissue. (
  • Approximately 50% of KIT/PDGFR WT show high expression of insulin-like growth factor 1 receptor (IGFR1). (
  • This expression may correlate also with the loss of SDH due to IGF autocrine loop26. (
  • The latter finding is consistent with (3) the decreased absolute and specific force measured in the EDL muscle in vitro and (4) the decreased charge movement and peak intracellular Ca2+ mobilization in individual muscle fibers from old IGF-I Tg mice compared to young wild-type mice, which also is associated with (5) decreased dihydropyridine receptor α1-subunit expression in old compared to young IGF-I Tg mice. (
  • Shved et al, 2005 & Eppler et al, 2005 studied expression patterns of IGF-I in various stages of development in bony fishes with limited emphasis on Oreochromis species. (
  • We evaluated IR isoforms expression in human carotid atherosclerotic plaques by consecutive immunoprecipitations of insulin receptor isoform B (IRB) and IRA. (
  • Western blot analysis was performed to measure IGF-IR, IGF-IIR, and α-smooth muscle actin (α-SMA) expression in human plaques. (
  • Moreover, complicated plaques showed a reduced IGF-IR expression, an increased IGF-IIR expression, and lower levels of α-SMA indicating a loss of VSMCs. (
  • IGF-I, IGFBP-3, and an acid labile subunit form a 150-kDa ternary complex that prolongs the plasma half-life of IGF-I and limits the amounts of free, biologically active IGF-I in circulation. (
  • 14. An antibody-nerve growth factor conjugate wherein said conjugate is bindable to transferrin receptors on brain capillary endothelial cells. (
  • Type 1 IGF receptor mRNA was detected in endothelial cells, indicating that these cells are a local target for IGF actions in liver. (
  • In addition, receptors for IGF-I and IGF-II and their structures are reported to be similar to known vascular cells, In the area of biological activities, however, the effects of IGFs on vascular cells are multiple, One unusual function of the IGF-I receptor in endothelial cells could be the involvement of transcytosis of IGF-I across the endothelium. (
  • Nuclear CREB3L3 mutually activates the peroxisome proliferator-activated receptor (PPAR) α promoter in an autoloop fashion and is crucial for the ligand transactivation of PPARα by interacting with its transcriptional regulator, peroxisome proliferator-activated receptor gamma coactivator-1α. (
  • Although it is highly homologous to G-PROTEIN-COUPLED RECEPTOR KINASE 2, it is not considered to play an essential role in regulating myocardial contractile response. (
  • Analysis of 570 random Y53G8 M13 subclone DNA sequences from the Genome Sequencing Center revealed that four sequences (00667, 00622, 00318, and 00706) were homologous to regions of the mammalian insulin receptor family. (
  • Increased responsiveness of vascular cells to the growth factor IGF-I has been implicated in complications associated with diabetes. (
  • Here we describe the development of an assay and screening of a library of compounds for their ability to accelerate cleavage of the transmembrane protein integrin-associated protein (IAP) thereby disrupting the association between IAP and SHPS-1 which we have shown as critical for the enhanced response of vascular cells to IGF-I. The cell-based ELISA utilizes an antibody that specifically detects cleaved, but not intact, IAP. (
  • This is generally attributed to the adverse effects of hyperglycemia and oxidative stress on vascular biology ( 2 ). (
  • it depends on fat depots (visceral or subcutaneous), the cell type composition (mature adipocytes, stromal-vascular cells, and nonfat cells including macrophages), and so on. (
  • Individuals with pre-diabetes, undiagnosed type 2 diabetes, and long-lasting type 2 diabetes are at high risk of all complications of macrovascular disease, coronary heart disease (CHD), stroke, and peripheral vascular disease. (
  • There are profound interactions between IGF-I and the renin-angiotensin system with respect to vascular resistance. (
  • Vascular smooth muscle cells (SMCs) have been shown to contain insulin-like growth factor I (IGF-I) receptors and respond to IGF-I with increases in DNA and protein synthesis ( 1 - 3 ), as well as cell migration ( 4 , 5 ). (
  • In addition, IGF can stimulate both metabolic and growth-promoting activities in cultured vascular cells. (
  • However, IGFs' biological effects appear to be much more potent in microvascular cells than in macrovascular cells, The interest in IGFs' effect on vascular cells is derived mainly from the possibility that they could be responsible for some of the vascular complications of diabetes, The clinical and animal studies involving IGFs and their possible roles in the development of diabetic proliferative retinopathy and glomerular sclerosis have been reviewed. (
  • 27 Angiogenesis is also induced in malignant endometrial cells and hyperplastic endometrial cells through activation of vascular endothelial growth factor (VEGF) and VEGF receptors. (
  • Early clinical data from anti-IGF-1R trials were awaited with bated breath-and they did not disappoint. (
  • Two large phase III trials of figitumumab were closed due to futility or potential futility, major toxicities have become apparent, and several drug companies have curtailed or totally eliminated their anti-IGF-1R programs. (
  • One has to wonder why it is, given the large literature on the absolute requirement of IGF-1R for mitogenesis and tumorigenesis,[1] that IGF-IR positivity is not used as an enrollment criteria for all anti-IGF-1R trials (similar to the restriction to HER2-positive disease in the development of trastuzumab). (
  • In addition, the authors comment on the need to combine anti-IGF-1R therapies with chemotherapy, but there are several important nuances to this approach that deserve mention. (
  • An exploratory cohort of an additional up to 10 subjects with prior exposure to anti-IGF-1R therapy and who have progressed or recurred after at least one prior chemotherapy regimen will also be assessed. (
  • If a total of two or more responses (partial and complete) in EFTs/DSRCTs are documented in this or the ongoing phase 1 study (20050118), then the study will allow enrollment of up to 10 additional EFT/DSRCT subjects who have been exposed to prior anti-IGF-1R targeting therapy. (
  • Subjects with relapsed Ewing's Family Tumors (EFTs) and Desmoplastic Small Round Cell Tumors (DSRCTs) who have not received prior anti-IGF-1R therapy will receive AMG 479 at 12mg/kg. (
  • A protein-tyrosine kinase receptor that is closely related in structure to the INSULIN RECEPTOR. (
  • AMG 479 inhibits the binding of both IGF-1 and IGF-2 to IGF-1R, thus inhibiting ligand‑dependent receptor activation. (
  • Structural basis for σ receptor ligand recognition. (
  • Ligand-directed serotonin 5-HT receptor desensitization, β-arrestin recruitment, and sensitization. (
  • Their insulin levels are not significantly different from those of wild-type mice ( 5 ), although Brüning et al. (
  • These mice are unique in that they do not have white fat but do develop type 2 diabetes. (
  • S1/2 −/− mice show enhanced cortex (Cx)-dependent remote fear memory formation as well as improved reversal learning, but do not display alterations in hippocampus (Hi)-dependent recent fear memory formation. (
  • A new Joslin-led study has identified the insulin receptor as an important protein that promotes islet cell growth in mice whose bodies are unable to use insulin properly, or are insulin resistant, a precursor to type 2 diabetes. (
  • In spite of their insulin resistance, the mice didn't show an appropriate growth response in the islets because the beta cells lacked insulin receptors. (
  • Both these mouse models were then compared to a control group of mice normally expressing both insulin and IGF-1 receptors in their beta cells. (
  • BALB c mice were immunized with rIGF-II receptors purified from 18-54, SF cells by chromatography of solubilized receptors over agarose-immobilized rIGF-II. (
  • The in vivo actions of insulin-like growth factor-I (IGF-I) on the growth and development of the hippocampal dentate gyrus were investigated in transgenic mice that overexpress IGF-I postnatally in the brain and in normal nontransgenic littermate controls. (
  • These transgenic mice, therefore, provide a unique opportunity to investigate the in vivo role of IGF-I in controlling the final number of neurons and synapses generated in the dentate gyrus during postnatal development. (
  • Amelioration of diabetes by hepatic activation of CREB3L3 was also observed in several types of diabetic obese mice. (
  • While the association with inhaled insulin was inconclusive, this issue is going to require special vigilance for any inhaled insulin delivery system "until concerns about the effects of high concentrations of insulin on local IGF-I receptors are resolved," they wrote in the editorial. (
  • Rates of secretion of IGF-I from isolated, perfused rat liver are sufficient to account for the concentrations of IGF-I found within the circulation ( 31 ). (
  • When used in high concentrations, it can activate the INS receptor, and can even complement the effects that INS has on the body. (
  • IGFBP-2 can act as a weak stimulator of IGF-I action in the presence of high concentrations of IGF-I ( 15 ). (
  • To determine whether these effects were caused by alterations in receptor kinase activity, the IGF-I receptor was immunoprecipitated and then analyzed for phosphotyrosine. (
  • We conclude that occupancy of the αVβ3 integrin is necessary for IGF-I to fully activate the kinase activity of the IGF-I receptor and phosphorylate IRS-1. (
  • At birth, IR-deficient homozygous null ( IR -/- ) pups could not be distinguished from their wild-type or heterozygous littermates, but IR deficiency leads to a number of major metabolic alterations soon after suckling begins. (
  • The incidence of metabolic disorders, including type 2 diabetes (T2D) and obesity-related insulin resistance, is increasing at alarming rates worldwide, largely due to poor lifestyle habits. (
  • Using DNA microarray technology, the researchers found that the single life-extending mutation - a change in the gene known as daf-2-exerts its influence through antimicrobial and metabolic genes, through genes controlling the cellular stress response, and by dampening the activity of specific life-shortening genes. (
  • The insulin-like growth factor 1 receptor (IGF1R) and the insulin receptor (IR) are receptor tyrosine kinases that are expressed in cancer cells. (
  • For instance, the SV40 large T antigen, H-Ras , EWS/FLI-1 , and c-Src transform wild type, but not Igf1r null, MEFs ( 1 - 4 ). (
  • By comparison, in situ hybridization revealed IGF-I mRNA only in the medullary thick ascending limbs while IGF-II mRNA was localized to the wall of the renal microvasculature in all kidneys. (
  • IGF-II mRNA was evaluated by in situ hybridisation method and ER, PR by immunohistochemistry. (
  • Studies involving in situ hybridisation have revealed that both IGF-I and IGF-II mRNA are produced predominantly in cells of mesenchymal origin. (
  • IGF-I or somatomedin C is a mitogen that mediates the growth-stimulatory effects of growth hormone throughout childhood and adolescence. (
  • In the body, insulin-like growth factor (IGF-1) is produced in response to growth hormone, and as a Receptors for growth hormone and IGF-1 were isolated from human skin, indicating that growth (Nutrition, 2001). (
  • Growth hormone (GH) is a major determinant of levels of circulating IGF-I and abundance of hepatic class 1 and class 2 IGF-I mRNAs ( 13 , 14 ). (
  • Insulin and insulin-like growth factor (IGF)-1 coupled with growth hormone helps control timing of sexual maturation. (
  • IGF-1 is produced primarily by the liver in response to the stimulation of growth hormone. (
  • The GHR gene provides instructions for making a protein called the growth hormone receptor. (
  • The growth hormone receptor has three major parts: An extracellular region that sticks out from the surface of the cell, a transmembrane region that anchors the receptor to the cell membrane, and an intracellular region that transmits signals to the interior of the cell. (
  • Growth hormone and IGF-I have a wide variety of effects on the growth and function of many parts of the body. (
  • Researchers have identified two major versions (isoforms) of the growth hormone receptor. (
  • All of the identified mutations impair the function of the growth hormone receptor. (
  • Most of the mutations affect the extracellular region of the receptor, preventing it from binding to growth hormone effectively. (
  • Although people with GHR gene mutations produce growth hormone, the defective receptors prevent cells from responding to the hormone by producing IGF-I or triggering cell growth and division. (
  • The two isoforms of the growth hormone receptor have been studied in several conditions involving problems with growth. (
  • Some studies have found that children with these disorders respond differently to treatment depending on which isoform of the growth hormone receptor they have. (
  • THOUSAND OAKS, Calif., June 4 /PRNewswire-FirstCall/ -- Amgen ( NASDAQ: AMGN ) today announced results from a small, randomized, placebo-controlled Phase 2 study indicating that adding AMG 479 to gemcitabine improved overall survival at six months (primary endpoint) and progression-free survival in patients with metastatic pancreatic cancer. (
  • Metformin treatment reduces the risk of pancreatic cancer in patients with type 2 diabetes. (
  • In the United States, 43,920 pancreatic cancer patients are diagnosed each year, resulting in approximately 37,390 deaths [ 2 ]. (
  • Possible mechanism of activation of ERK1/2 and AP-1 in skeletal muscles. (
  • Schematic representation of the potential mechanism of activation of ERK1/2 and AP-1 transcription factor in response to mechanically loading of skeletal muscles either axially or transversely as supported by the data. (
  • The two isoforms differ by the presence or absence of a particular segment known as exon 3, which is located in the extracellular region of the receptor. (
  • Obesity has increased dramatically over the past 20 years in the United States ( 1 ) and in other developed countries and is associated with increased incidence ( 2 , 3 ) and mortality rates ( 4 ) of various cancers. (
  • In this issue of ONCOLOGY, Golan and Javle provide an excellent update on targeting the insulin-like growth factor 1 receptor (IGF-1R) in gastrointestinal cancers. (
  • However, type 2 diabetes is also associated with a constellation of additional risk factors, such as obesity, dyslipidemia, and hypertension, which concur to promote CVD. (
  • In addition to increased body adiposity and secretion of fat-derived hormones, obesity is also linked to insulin resistance, type 2 diabetes, and chronic inflammation. (
  • Moreover, the novel finding of this study is that while IGF-1 receptor-mediated Akt activation contributes to cardiac hypertrophy, it is not involved in mTOR activation and autophagy suppression in obesity and T2DM. (
  • BACKGROUND: Obesity is a global phenomenon and is associated with various types of cancer, including colon cancer. (
  • elevated during obesity) and elucidated the mechanisms of action using IGF-1R siRNA in HT-29 cells which represents advanced colon carcinogenesis. (
  • 6 Obesity has been associated with a 2-5 fold increased risk in endometrial cancer. (
  • Affected individuals appear to develop these common diseases much less frequently than their unaffected relatives, despite having obesity (a risk factor for both cancer and type 2 diabetes). (
  • As demonstrated for human IGFBP-5, the N terminus is the primary binding site for IGF. (
  • For example, IGFBP-5 stimulates markers of bone formation in osteoblasts lacking functional IGFs [ PMID: 11874691 ]. (
  • GH receptor was expressed in all cell preparations, consistent with GH regulation of IGF-I and IGFBP synthesis in multiple liver cell types. (
  • IGFBP-4, in contrast, is usually a negative regulator of IGF-I action ( 16 , 17 ). (
  • People with both type 1 and type 2 diabetes develop atherosclerosis at a significantly accelerated rate compared to non diabetics [ 17 - 19 ]. (
  • RESULTS In comparison to NGT, CD34+ cells were significantly reduced in IGT and had a first nadir in newly diagnosed type 2 diabetes and a second nadir after 20 years of diabetes. (
  • Plasma testosterone fell significantly in both sexes (male: 15·0 ± 1·3 vs. 11·3 ± 1·2 nmol/l, P 0·01, female: 1·8 ± 0·5 vs. 0·5 ± 0·1 nmol/l, P 0·05). (
  • Studies suggest that people with Laron syndrome have a significantly reduced risk of cancer and type 2 diabetes. (
  • It stimulates the synthesis and release of endogenous GH, with an increase in level of insulin-like growth factor (IGF-1). (
  • Knockdown of InsR and/or insulin-like growth factor-I receptor (IGF-IR) inhibited growth of 3 of 4 LTED cell lines. (
  • The newly identified resistin receptor, CAP1, was expressed across a large panel of breast cancer cell lines and primary breast tumors. (
  • The present study was designed to describe the extent and potential mechanisms of progenitor cell reduction during the natural history of type 2 diabetes. (
  • CONCLUSIONS Circulating progenitor cell reduction marks the clinical onset of type 2 diabetes. (
  • 2 Center for Integrative Genomics and Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. (
  • Using a range of experimental stem and cell type-specific systems in human and model organisms, York Biomedical Research Institute researchers study the processes of development, differentiation and regeneration. (
  • Human IGF-II belongs to a family of growth factors that includes insulin, relaxin, and insulin-like growth factor I (IGF-I). Members of the family share limited sequence homology but are presumed to exhibit similar structures on the basis of aconserved pattern of disulphide bond formation (Dafgard et al, Journal of Cell Science, 3:53-64 (1984). (
  • Insulin exerts its effects by interaction with a cell-surface receptor, which may also result in the promotion of cell growth [ PMID: 6243748 ]. (
  • RESULTS: Resveratrol (100-150 microM) exhibited anti-proliferative properties in HT-29 cells even after IGF-1 exposure by arresting G0/G1-S phase cell cycle progression through p27 stimulation and cyclin D1 suppression. (
  • Two IGF-I mRNA subtypes with different 5′ ends (class 1 and class 2) were detected in all isolated liver cell preparations. (
  • The liver has not been traditionally considered a major target tissue for IGF-I actions because hepatocyte cell membranes contain few type 1 IGF receptors and type 1 IGF receptor mRNA is not readily detected in poly(A) + RNA prepared from whole rat liver ( 23 , 26 ). (
  • Because hepatocytes represent the majority of cells within the liver, these observations do not exclude the possibility that type 1 IGF receptor is expressed in less abundant liver cell types. (
  • These two receptors have been a major focus of research studies by Dr. Kulkarni and others at Joslin Diabetes Center who want to better understand beta cell growth and functioning so that these essential cells can be increased in people with diabetes. (
  • By investigating the cellular mechanisms that affect islet cell growth and development, Joslin researchers hope to improve the process to better treat type 2 diabetes, the most common form of diabetes. (
  • This study investigated whether insulin receptors in the beta cell play a key role in promoting their growth as a response to overcome insulin resistance. (
  • In the first model, an insulin-resistant mouse was crossed with a mouse lacking insulin receptors in the beta cell. (
  • The resulting offspring had insulin resistance with no receptors in the beta cell. (
  • This provided genetic evidence that insulin receptors are important for the islet cell growth response to insulin resistance," said Dr. Kulkarni. (
  • They used two mouse models--beta-cell-specific insulin receptor knockouts (beta-IRKO), which lack insulin receptors in beta cells, and IGF-1 receptor knockout (beta-IGF1RKO), which lack IGF-1 receptors in beta cells. (
  • The results clearly showed that it is the insulin receptor -- not the IGF-1 receptor -- that is critical for the islet cell growth response to insulin resistance," said Dr. Kulkarni. (
  • More recently, IGF-I has been shown to have an antiapoptotic effect in this cell type ( 6 ). (
  • Natural killer cells are part of our immune system's rapid-response team against cancer cells, taking them out through the activation of cancer cell suicide via "death receptors. (
  • The treatment of H9c2 cardiomyoblast cells with IGF-II not only induced cell hypertrophy but also increased the protein level of ANP and BNP. (
  • The U-2 OS cell line, originally known as the 2T line, was derived from the bone tissue of a fifteen-year-old human female suffering from osteosarcoma. (
  • Moreover, although the U-2 OS cell line was derived from a female, boys, who typically grow more than girls, are about twice as likely to experience the disease. (
  • Golgi Network and Filamentous Actin in U-2 OS Cell Cultures - The adherent culture of human osteosarcoma (U-2 OS) cells illustrated in this section was stained with Oregon Green 488 conjugated to wheat germ agglutinin, a plant-derived lectin that targets the Golgi apparatus, as well as Alexa Fluor 568 conjugated to phalloidin for cytoskeletal actin. (
  • During my career I have been working ondifferent projects including: 1) The development of immunomodulatory cancervaccines to treat Acute Myeloid Leukaemia (AML) (Clinical Immunology),2)Investigation of the role of endogenous retroviruses in Multiple Sclerosis(MS)(Clinical Virology) and 3) Revealing the signalling of orexinergic receptorstowards cell fate determination(Neuroscience). (
  • 0004] On the other hand, embryonic stem (ES) cells are pluripotent cells that are both self-renewing and have the capacity to differentiate into any cell type in the human organism. (
  • Otteson & Hitchcock at 2003 studied influence of IGFs in cell division and related functions. (
  • Thus, we demonstrate for the first time that Ang-(1-7) counteracts the skeletal muscle atrophy induced by AngII through a mechanism dependent on the Mas receptor, which involves AKT activity. (
  • The prognosis of patients with type 2 diabetes is highly dependent on the presence of CVD. (
  • Major molecular abnormalities in breast cancer include the deregulation of several components of the IGF system. (
  • A better understanding of IGF system signal diversification in breast cancer has important implications for cancer prevention measures, which should include control of insulin resistance and associated hyperinsulinemia. (
  • Phosphorylated InsR/IGF-IR is present in all breast cancer subtypes, and high levels have been correlated with poor survival ( 7 ). (
  • Furthermore, type II diabetes and hyperinsulinemia are associated with increased breast cancer risk, and use of an inhaled form of insulin in patients with type I diabetes has been linked with breast cancer development ( 1 ). (
  • Increased body fatness poses a major risk for developing several types of cancer, including breast cancer ( 2 , 3 ). (
  • In breast cancer, insulin-like growth factor II (IGF-II) is stromal in origin and is considered an important regulator of tumour epithelium growth. (
  • Numerous studies document both molecular and genetic factors as initiators and promoters of breast tissue oncogenesis [ 2 ]. (
  • The early effects of glucocorticoids on skeletal muscle (SkM) androgen and IGF-1 pathways have not been previously investigated in human subjects. (
  • Genetic analysis of daf mutants, which arrest at the dauer stage or enter the reproductive life cycle independent of pheromone regulation, has revealed that parallel genetic pathways regulate distinct aspects of the dauer metamorphosis ( 2 ). (
  • Insulin-like Growth Factor II (IGF-II) analogues in which at least one of R37 and R38 is replaced with another amino add residue, the most preferred being IGF-II R37Q R38Q, can readily be produced in E. coli, unlike natural IGF-II, which is cleaved on secretion. (
  • Since the body's natural response to insulin resistance is to increase insulin secretion from the pancreas and grow more islet cells, also known as beta cells, harnessing this growth response could lead to new treatments for type 2 diabetes. (
  • Changes in IGF-I receptor number have been determined, but they are usually minimal and are associated with a decrease in IGF-I synthesis and secretion ( 7 ). (
  • The predicted DAF-2 protein is 35% identical to the human insulin receptor, 34% identical to the human insulin-like growth factor-I (IGF-I) receptor, and 33% identical to the human insulin receptor-related receptor ( 4 ). (
  • Because it is equally distant from the human insulin, IGF-I, and insulin receptor-related receptors, DAF-2 is probably the homolog of the ancestor of these duplicated and diverged receptors, and thus may subserve any or all of their functions. (
  • An enrichment of PIK3CA exon 20 mutations was observed in progesterone receptor- positive tumors. (
  • IGFs are peptide hormones secreted from many different cells and their "insulin-like" designation originated from experiments in which treatment of serum with antibodies to insulin failed to eliminate all insulin activity. (
  • There are two principle IGFs, IGF-I and IGF-II, that have characteristics of both growth factors and hormones. (
  • Kenyon's team discovered ten years ago that a single mutation in the daf-2 gene, which encodes a hormone receptor similar to the human receptors for the hormones insulin and IGF-1, doubled the worms' lifespan. (