• We recently reported that genetic or pharmacological inhibition of insulin-like growth factor receptor (IGF-1R) slows DNA replication and induces replication stress by downregulating the regulatory subunit RRM2 of ribonucleotide reductase, perturbing deoxynucleotide triphosphate (dNTP) supply. (nature.com)
  • IGF-1 binds IGF-IR, IGF-IIR, and the insulin receptor and plays a key role in cell cycle progression, cell proliferation and tumor progression. (joplink.net)
  • Control fibroblasts exhibited the usual affinity labeling of the disulfide-linked Mr = 350,000 insulin and IGF-I receptor structures. (diabetesjournals.org)
  • These observations suggest that a common genetic defect alters the expression of the homologous receptor structures for insulin and IGF-I. (diabetesjournals.org)
  • The Insulin Receptor (INS R) and insulin-like growth factor-1 receptor (IGF-1 R) constitute a subfamily of receptor tyrosine kinases (1‑4). (rndsystems.com)
  • The intracellular region contains the kinase domain sandwiched between the juxtamembrane domain used for docking insulin-receptor substrates (IRS), and the carboxy-terminal tail that contains two phosphotyrosine-binding sites. (rndsystems.com)
  • The cation-independent mannose 6-phosphate (M6P)/Insulin-like growth factor-2 receptor (CI-MPR/IGF2R) is an ∼300 kDa transmembrane protein responsible for trafficking M6P-tagged lysosomal hydrolases and internalizing IGF2. (ox.ac.uk)
  • IGF-I deficiency can be the result of GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency (growth hormone receptor deficiency [GHRD], Laron syndrome) or postreceptor defects, including the principal transduction agent STAT5b, the IGF-I/IGFBP3 stabilizer acid labile subunit (ALS), the IGF-I gene, or the IGF-I receptor. (medscape.com)
  • IGF binding involves 3 basic types of receptors: the structurally homologous insulin receptor and type 1 IGF receptor and the distinctive type 2 IGF-II/mannose-6-phosphate receptor. (medscape.com)
  • In addition to these receptors, hybrid receptors consisting of a dimer from the IGF-I receptor paired with the insulin receptor, are ubiquitous and the respective expression of these receptors varies from tissue to tissue. (medscape.com)
  • Although the insulin receptor has a low affinity for IGF-I, IGF-I is present in the circulation at molar concentrations that are 1000 times those of insulin. (medscape.com)
  • The overexpression of miRNA‑375 significantly suppressed the levels of protein expression of ubiquitin‑protein ligase E3A (UBE3A) and Insulin‑like growth factor‑1 receptor (IGF‑1R) in HPV‑18(+) cervical cancer cells. (spandidos-publications.com)
  • In breast cancer and head and neck squamous cell carcinoma cells, we are examining IGF-1 receptor crosstalk to vascular endothelial growth factor (VEGF) signaling in mediating enhanced tumorigenicity and metastasis. (musc.edu)
  • Using retinal pigment epithelial cells as a model, we are studying the interplay between IGF-1 receptor signaling and hypoxia in the regulation of vascular endothelial growth factor production and the loss of intercellular tight junctions. (musc.edu)
  • The IGFBPs are a class of six homologous secretory proteins, which function to block access of the IGFs to the IGF-1 receptor. (musc.edu)
  • Furin (PACE, paired basic amino acid cleaving enzyme, membrane associated receptor protein) is serine endoprotease responsible for processing a variety of substrates (proparathyroid hormone, transforming growth factor beta 1 precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-nerve growth factor and von Willebrand factor). (eu.org)
  • IGF-1 only binds to insulin receptor at extremely high doses, as IGF-1 has 100 fold higher affinity for IGF-1R compared to insulin receptor [16]. (m2cobalt.com)
  • IGF-2 usually binds to insulin receptor during fetal development, as later in development when IGF-1R is usually expressed, IGF-2 binds to IGF-1R more tightly [16,17]. (m2cobalt.com)
  • IGF-1 is the favored ligand for IGF-1R/insulin receptor hybrid receptors compared to insulin, as IGF-1 can tightly bind in the presence of only one subunit of the MRT-83 hemireceptor, while insulin requires two subunits of the hemireceptor to provide optimal binding [16]. (m2cobalt.com)
  • Insulin receptor and IGF-1 receptor are both tyrosine kinases. (m2cobalt.com)
  • Insulin receptor and IGF-1R are homologous and form hemireceptors. (m2cobalt.com)
  • it binds to insulin MRT-83 receptor only at very high concentrations. (m2cobalt.com)
  • IGF-2 binds to IGF-1R, MRT-83 IGF-2R and binds to insulin receptor only during early fetal development. (m2cobalt.com)
  • Insulin binds to insulin receptor, and it binds to IGF-1R/Insulin Receptor hemireceptor at high concentration. (m2cobalt.com)
  • Signal transduction is usually activated after the activation of IGF-1R, IGF-1R/Insulin Receptor hemireceptor and insulin. (m2cobalt.com)
  • Glioblastoma (GBM), a very aggressive and incurable tumor, often results from constitutive activation of EGFR (epidermal growth factor receptor) and of phosphoinositide 3-kinase (PI3K). (sdbonline.org)
  • A molecular understanding of membrane traffic has broad implications for our understanding of growth control in cancer, receptor trafficking errors in heart disease, regulation of insulin secretion in diabetes and synaptic vesicle biogenesis and transport in neurological disorders. (stanford.edu)
  • Insulin-like growth factor I (IGF1) belongs to the family of insulin-like growth factors that are structurally homologous to proinsulin. (joplink.net)
  • The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. (joplink.net)
  • The receptors for insulin and the insulin-like growth factor (IGF) I are two structurally homologous disulfide-linked multisubunit complexes of apparent Mr = 350,000. (diabetesjournals.org)
  • Insulin-like growth factor (IGF)-I (also known as somatomedin C and somatomedin A) and IGF-II (multiplication stimulating activity or MSA) belong to the family of insulin-like growth factors that are structurally homologous to proinsulin. (reliatech.de)
  • These studies have profound implications for the development of IGF-1 antagonists by designing small molecular weight analogs, structurally identical to the binding site for use in inhibiting the growth of IGF-dependent tumors. (musc.edu)
  • They are, however, slightly different from insulin structurally by made up of an additional domain name, which could account for their dramatically different role in neoplasms in comparison with insulin [16]. (m2cobalt.com)
  • Preptin is present in islet beta-cells, undergoes glucose-mediated co-secretion with insulin, and acts as a physiological amplifier of glucose-mediated insulin secretion. (wikipedia.org)
  • c Somatostatin's effects on metabolism are indirect via suppression of secretion of insulin, glucagon, growth hormone, and thyroid hormone and by effects on gastric acid secretion, gastric emptying time, and pancreatic exocrine secretion (see text). (basicmedicalkey.com)
  • For several years, researchers have focused on the role of insulin-like growth factor (IGF)-1 as a primary signaling molecule that mediates skeletal-muscle growth in response to resistance exercise, given that resistance exercise stimulates the secretion of IGF-1. (humankinetics.com)
  • What factors decrease GH secretion? (flashcardmachine.com)
  • Ngenla ® (somatrogon-ghla): The FDA has approved Pfizer's Ngenla (somatrogon-ghla), a once-weekly, human growth hormone analog indicated for treatment of pediatric patients aged three years and older who have growth failure due to inadequate secretion of endogenous growth hormone. (primetherapeutics.com)
  • Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. (justia.com)
  • In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs. (justia.com)
  • To track differentiating cell populations, reporter cell lines generated by homologous recombination (knock-in) or via BAC transgenes have been widely used in mouse cells (5-8 ). (lu.se)
  • Many cancers show aberrant signalling via the insulin-like growth factor (IGF) axis, activating type 1 IGF receptors (IGF-1Rs) and variant insulin receptors (INSRs) to signal via phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) and mitogen-activated protein kinase kinase-extracellular signal-regulated kinases (MEK-ERK) [ 1 ]. (nature.com)
  • The receptors for IGF-I and insulin in skin fibroblasts from this patient were affinity labeled with 125 I-IGF-I and 125 I-insulin, respectively, and visualized by electrophoresis and autoradiography in polyacrylamide gels. (diabetesjournals.org)
  • Background and Purpose The ATP-binding cassette transporter A-1 (ABCA1) gene is a key target of the transcription factors liver-X-receptors (LXRs). (bioinf.org)
  • Open in a separate windows Physique 1 Binding of insulin and IGF ligands to their receptors. (m2cobalt.com)
  • The exchange of GDP to GTP and thus the activation of Rho GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), which act downstream of numerous growth factor receptors, integrins, cytokine receptors, and cadherins. (biomedcentral.com)
  • The insulin-like growth factor binding proteins (IGFBPs) comprise a family of six distinct proteins which modulate insulin-like growth factor action. (eur.nl)
  • This review summarizes evidence for the role of proteolytic enzymes that degrade and inactivate insulin-like growth factor binding proteins (IGFBP) during follicular development in mammals. (bioone.org)
  • The most critical of these proteins is the signal transducer and activator of transcription 5b (STAT5b), which couples GH binding to the activation of gene expression that leads to the intracellular effects of GH, including synthesis of IGF-I, insulin-like growth factor binding protein 3 (IGFBP3), and ALS. (medscape.com)
  • In addition, numerous important cellular proteins, such as B-cell lymphoma-2 homologous antagonist/killer, Myc proto-oncogene protein, cyclin-dependent kinase inhibitor 1B, DNA replication licensing factor MCM-7, retinoblastoma 1 and Annexin A1, are degenerated through the UBE3A-mediated ubiquitin proteasome pathway ( 7 ). (spandidos-publications.com)
  • Its substrates include transforming growth factor beta-related proteins, proalbumin, and von Willebrand factor. (eu.org)
  • The major role of IGF-2 is as a growth promoting hormone during gestation. (wikipedia.org)
  • IGF-1 expression is regulated by growth hormone. (joplink.net)
  • IGF-1 is a hormone homologous to insulin, so-called insulin-like growth factor. (yephealth.net)
  • It also acts as a growth hormone (GH) mediator promoting chondroblasts, fibroblasts and myoblasts mitosis and myocytes hypertrophy, which results in bone and muscle growth of the organism. (yephealth.net)
  • In mammals, the order in which the hormones act is unresolved because insulin, insulin-like growth factor-1, growth hormone, and thyroid hormones are interdependent. (scite.ai)
  • The aging process is characterized metabolically by insulin resistance, changes in body composition, and physiological declines in growth hormone (GH), insulin-like growth factor-1 (IGF-1), and sex steroids. (scite.ai)
  • Growth hormone (GH) is a key determinant of postnatal growth and plays an important role in the control of metabolism and body composition. (scite.ai)
  • Insulin-like growth factor I (IGF-I) is the effector of growth induced by growth hormone (GH). (medscape.com)
  • Epinephrine , norepinephrine , cortisol , somatostatin , and growth hormone also have contrainsular activity. (basicmedicalkey.com)
  • Thyroid hormone also must be classified as an insulin counterregulatory hormone because it increases the rate of fuel consumption and also increases the sensitivity of the target cells to other insulin counterregulatory hormones. (basicmedicalkey.com)
  • IGF-1 & 2 are somewhat homologous to what other hormone? (flashcardmachine.com)
  • Which hormone (GH or IGF-1) increases tissue sensitivity to insulin? (flashcardmachine.com)
  • Insulin-like growth factor 2 (IGF-2) is one of three protein hormones that share structural similarity to insulin. (wikipedia.org)
  • In T2's with twice the protein consumption and equicaloric carbohydrate consumption (30% protein, 30% carb, 40% fat) the 24-hour glucose exposure decreased as the insulin exposure increased with specific mention of increasing IGF-1 inhibiting endogenous glucose production. (blogspot.com)
  • IGFBP7, also known as mac25, prostacyclin-stimulating factor (PSF), tumor adhesion factor (TAF), and angiomodulin (AGM), is a secreted protein that belongs to the insulin-like growth factor (IGF)-binding protein (IGFBP) family. (biofargo.com)
  • cell figures, protein and mRNA expression were analyzed using two-factor ANOVA followed by post-hoc Bonferroni test. (bioinf.org)
  • The protein is required for processing of precursors of alpha-factor and killer toxin. (eu.org)
  • Mutations in the INS R gene have been linked to insulin-resistant diabetes mellitus, noninsulin-dependent diabetes mellitus and leprechaunism, an extremely rare disorder characterized by abnormal resistance to insulin that results in a variety of distinguishing characteristics, including growth delays and abnormalities affecting the endocrine system. (rndsystems.com)
  • It is well known that the primary factor determining the hypertrophic response to contractile activity is the load across the muscle or the mechanical stretch/strain imposed on the muscle fibers, which is higher in resistance exercise than in endurance exercise. (humankinetics.com)
  • PCOS involves various pathophysiological factors, and affected women usually have significant insulin resistance (IR), which is a major cause of PCOS. (biomedcentral.com)
  • PCOS is a heterogeneous disease characterized by hyperandrogenism, dysfunctional ovulation, and polycystic ovary morphology, accompanied by metabolic abnormalities, such as insulin resistance (IR) and obesity. (biomedcentral.com)
  • In addition to the structural similarity with insulin, they are considered anabolic hormones for increasing the uptake of glucose and amino acids by the muscle fibers. (yephealth.net)
  • Two factors concur to determine specific Rho GTPase function: tissue specificity of GTPase effectors and distinct intracellular localizations of closely related Rho GTPases, due to different lipid modifications [ 1 ]. (biomedcentral.com)
  • In the nematode and the fly, secondary hormones downstream of insulin-like signaling appear to regulate aging. (scite.ai)
  • a Hormones with actions that are generally opposed to those of insulin. (basicmedicalkey.com)
  • It is believed to be a major fetal growth factor in contrast to insulin-like growth factor 1 (IGF-1), which is a major growth factor in adults. (wikipedia.org)
  • Primiparous ewes ( n =32) were assigned to dietary treatments in a 2×2 factorial arrangement to determine effects of nutrient restriction and melatonin supplementation on maternal and fetal pancreatic weight, digestive enzyme activity, concentration of insulin-containing clusters and plasma insulin concentrations. (cambridge.org)
  • Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. (joplink.net)
  • Solution hybridization/ribonuclease protection analysis of total RNA isolated from serum-free monolayer cultures of porcine granulosa cells revealed that insulin (3 μg/ml) increased HMG-CoA messenger RNA (mRNA) concentrations corrected for constitutive 18S ribosomal RNA expression in a time-dependent fashion, with significant effects observed at 12 h and a 6-fold increase by 48 h. (elsevierpure.com)
  • Insulin concentrations in plasma from the uterine vein, umbilical artery and umbilical vein were greater ( P ⩽0.01) in animals receiving 100% requirements. (cambridge.org)
  • As serum-free monolayer culture of (swine) granulosa cells offers an in vitro model of hormonally responsive HMG-CoA reductase, we generated a (porcine) complementary DNA and homologous complementary RNA to investigate by sensitive and specific ribonuclease protection assay the hormonal regulation of HMG-CoA reductase gene expression in ovarian cells from immature Graafian follicles. (elsevierpure.com)
  • We conclude that insulin alone or in combination with FSH or cAMP augments the accumulation of HMG-CoA reductase mRNA in ovarian (granulosa) cells. (elsevierpure.com)
  • Given the ability of IGF-I to mimic insulin action in the present studies and the putative intrafollicular role of IGF-I, we postulate that synergistic stimulation of the expression of HMG-CoA reductase gene transcript levels in vivo simultaneously by insulinomimetic peptides and activators of the cAMP signal transduction pathway can help meet the demand for increased sterol substrate by differentiating granulosa cells. (elsevierpure.com)
  • It has an anabolic impact on bone growth and exhibits osteogenic properties, increasing osteoblast mitogenic activity through phosphoactivation of MAPK1 and MAPK3. (wikipedia.org)
  • Phosphoinositide 3-kinase (PI3K) signaling contributes to a variety of processes, mediating many aspects of cellular function, including nutrient uptake, anabolic reactions, cell growth, proliferation, and survival. (mdpi.com)
  • PCSK1 (proprotein convertase 1, NEC1) and PCSK2 (proprotein convertase 2, NEC2) are type I proinsulin-processing enzymes that play a key role in regulating insulin biosynthesis. (eu.org)
  • Their names are based on the observation that both IGF-1 and IGF-2 are peptides, much like insulin, and they share MRT-83 40% homology with proinsulin [15,16]. (m2cobalt.com)
  • Reduced signaling of insulin-like peptides increases the life-span of nematodes, flies, and rodents. (scite.ai)
  • Despite the similarities among mammals and invertebrates in insulin-like peptides and their signal cascade, more research is needed to determine whether these signals control aging in the same way in all the species by the same mechanism. (scite.ai)
  • IR is present in all phenotypes, and insulin sensitivity varies according to the PCOS phenotype. (biomedcentral.com)
  • Therefore, recognizing the strong influence of IR on the occurrence and development of PCOS, accurate assessment of insulin sensitivity in the early stages of PCOS, and effective intervention on IR are essential to reduce the risk of long-term complications. (biomedcentral.com)
  • In addition, samples of pancreatic tissue were fixed in 10% formalin solution for histological examination including quantitative characterization of size and distribution of insulin-containing cell clusters. (cambridge.org)
  • Melatonin supplementation decreased ( P =0.002) maternal pancreatic insulin-positive tissue area (relative to section of tissue), and size of the largest insulin-containing cell cluster ( P =0.04). (cambridge.org)
  • Nutrient restriction decreased pancreatic insulin-positive tissue area ( P =0.03) and percent of large (32 001 to 512 000 µm 2 ) and giant (⩾512 001 µm 2 ) insulin-containing cell clusters ( P =0.04) in the fetus. (cambridge.org)
  • 0.001) pancreatic insulin-positive area (relative to section of tissue) and a greater percent of small, large and giant insulin-containing cell clusters ( P ⩽0.02). (cambridge.org)
  • However, the combined action of either FSH and insulin or 8-bromo-cAMP and insulin resulted in synergistic increases in reductase mRNA by 31- and 17-fold, respectively. (elsevierpure.com)
  • Brain-ABCA1 deficient mice exhibited increased the level of matrix-metalloproteinase-9 (MMP9) and reduced the level of insulin-like growth factor-1 (IGF1) in the ischemic brain. (bioinf.org)
  • INS R signaling is important in metabolic regulation, but may also contribute to cell growth, differentiation and apoptosis. (rndsystems.com)
  • Both the A and B isoforms bind insulin with high-affinity, but the A isoform has considerably higher affinity for IGF‑I and IGF-II. (rndsystems.com)
  • Genetic, environmental, behavioral and dietary factors influence the pathways that regulate aging and life expectancy, thus rendering longevity a very complex phenomenon. (iospress.com)
  • Overexpression of IGF-1 in serum and tissue alters the growth of normal cells and causes uncontrolled proliferation, inhibits differentiation and reduces apoptosis, resulting in the incidence and development of malignant tumors ( 10 ). (spandidos-publications.com)
  • Components of IGF Axis The insulin-like growth factor (IGF) pathway has highly conserved function in mammals and plays a critical role in energy metabolism and cell renewal in response to nutrients [6-11]. (m2cobalt.com)
  • Mutant embryonic fibroblasts fail to respond to insulin-like growth factor I (IGF) by the IGF-I-induced increase in cell number observed in wild-type cells. (aacrjournals.org)
  • This development occurs under the influence of macrophage colony-stimulating factor (M-CSF), which is secreted by various cell types (eg, endothelial cells, fibroblasts). (msdmanuals.com)
  • Co-inhibition of IGF and CHK1 caused synergistic suppression of cell viability, cell survival and tumour growth in 2D cell culture, 3D spheroid cultures and in vivo. (nature.com)
  • Recently, the insulin-like growth factor (IGF) axis has emerged as an important pathway in the development and progression of HCC and as a potential therapeutic target. (m2cobalt.com)
  • IGF pathway is Flt4 not only involved in cell MRT-83 growth in tissue culture [12,13], but it also promotes cell proliferation, migration and transformation into malignant clone [12,14]. (m2cobalt.com)
  • The large INS R extracellular domain is organized into two successive homologous globular domains, which are separated by a Cysteine-rich domain, followed by three fibronectin type III domains. (rndsystems.com)
  • The extracellular region of the CI-MPR has 15 homologous domains, including M6P-binding domains (D) 3, 5, 9, and 15 and IGF2-binding domain 11. (ox.ac.uk)
  • RT-qPCR The ipsilateral brain and the homologous areas from your sham brain (Physique 1A) and the harvested astrocyte-cultures were utilized for RT-qPCR. (bioinf.org)
  • Insulin-like growth factor-1 (IGF-1), synthesized and secreted by human hepatocytes, is the primary regulator of insulin and serves an important function in regulating the growth and development of the body ( 8 ). (spandidos-publications.com)
  • Some interventions designed to address features of aging, such as caloric restriction or visceral fat depletion, have succeeded in improving insulin action and life span in rodents. (scite.ai)
  • At infection sites, activated T cells secrete cytokines (eg, interferon-gamma [IFN-gamma]) that induce production of macrophage migration inhibitory factor, preventing macrophages from leaving. (msdmanuals.com)
  • We have examined this possibility in an insulinresistant, diabetic patient who exhibits decreased insulin binding activity. (diabetesjournals.org)
  • Our results show that each of the six mIGFBPs is highly homologous to their human and rat counterparts, whereas only the N and C terminal ends are conserved between the six mIGFBPs. (eur.nl)
  • Detects human Insulin R/CD220 in direct ELISAs. (rndsystems.com)
  • Human and mouse IGFBP7 are highly homologous, sharing 94% a.a. sequence identity. (biofargo.com)