• Stimulation of insulin secretion from pancreatic β-cells by glucagon-like peptide 1 receptor (GLP-1R) agonists is known to be glucose-dependent. (nih.gov)
  • GLP-1R agonists potentiate glucose-stimulated insulin secretion and have little or no activity on insulin secretion in the absence of elevated blood glucose concentrations. (nih.gov)
  • This review aims to discuss the current understanding of the mechanisms by which GLP-1R signalling promotes insulin secretion from pancreatic β-cells via a glucose-dependent process. (nih.gov)
  • Is the Subject Area "Insulin secretion" applicable to this article? (plos.org)
  • Glucagon secretion, insulin and IGF-IR autophosphorylation, and insulin receptor substrate (IRS)-1, IRS-2, phosphatidylinositol kinase (PI3K) (p85 alpha), and serine-threonine protein kinase (Akt) phosphorylated (active) forms were measured. (unict.it)
  • Basal glucagon secretion was increased and the inhibitory effect of acute insulin exposure reduced in alpha-TC1 cells cultured with palmitate. (unict.it)
  • In this study, we investigated the significance of β 2 - adrenergic receptor (β 2 AR) in age-related impaired insulin secretion and glucose homeostasis. (elsevierpure.com)
  • Interestingly, with aging, wild-type (β 2 AR +/+ ) littermates developed impaired insulin secretion and glucose tolerance. (elsevierpure.com)
  • Biochemically, the insulin receptor is encoded by a single gene INSR, from which alternate splicing during transcription results in either IR-A or IR-B isoforms. (wikipedia.org)
  • Immunoprecipitation assays revealed that insulin activated the insulin receptor (INSR), but not the IGF1 receptor (IGF1R). (scienceopen.com)
  • In conclusion, insulin exhibits direct mitogenic activities in PCa cells, which are mediated exclusively through the INSR. (scienceopen.com)
  • Genetic testing showed that the patient (proband), his mother , and his grandfather had a novel p.Val1086del heterozygous mutation in exon 17 of the insulin receptor gene (INSR). (bvsalud.org)
  • These changes facilitate the recruitment of specific adapter proteins such as the insulin receptor substrate proteins (IRS) in addition to SH2-B (Src Homology 2 - B ), APS and protein phosphatases, such as PTP1B, eventually promoting downstream processes involving blood glucose homeostasis. (wikipedia.org)
  • Insulin receptor substrate (IRS) proteins play essential roles in mediating insulin/IGF signaling by recruiting a series of downstream effectors 23 . (nature.com)
  • Since these intrinsically disordered regions, which are conformationally dynamic and do not adopt stable secondary or tertiary structures, are often essential for mediating the phase transition of proteins 9 , it is therefore of interest to consider if the C-terminus of IRS-1 is involved in phase separation and to further delineate such implications upon insulin/IGF signaling. (nature.com)
  • The IRS proteins function as adaptors and transmit signals from multiple receptors. (scielo.br)
  • The IRS proteins (IRS1-4) are the family of adaptors regulating metabolic and mitogenic signaling pathways ( Hanke and Mann , 2009 Hanke S and Mann M (2009) The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. (scielo.br)
  • Following insulin binding, the insulin receptor (IR) autophosphorylates itself and creates docking sites for IRS proteins. (scielo.br)
  • Immunoblot analysis of wheat germ agglutinin-agarose purified retinal membrane proteins revealed that retinas from diabetic rats expressed higher insulin receptor levels than retinas from control rats. (diabetesjournals.org)
  • Affinity labeling analysis of WGA-purified retinal membrane proteins indicated a 1.5-fold increase in neuronal and a 9% decrease in peripheral receptor subtypes, corroborating the immunoblot analysis. (diabetesjournals.org)
  • Both hormones are small proteins that are recognized by receptors on the surface of cells. (rcsb.org)
  • Insulin receptor substrate-2-deficient (IRS2-/-) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. (uam.es)
  • Here the possibility that this is accompanied by a corresponding episode of accelerated evolution of IGF1 receptor (IGF1R), insulin receptor (IR) and/or IGF binding proteins (IGFBPs) was investigated. (figshare.com)
  • The insulin receptor substrate (IRS) proteins are a family of cytoplasmic adaptor proteins recognized for their role in insulin signaling. (biomedcentral.com)
  • 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)
  • site 1, which binds to the 'classical' binding surface of insulin: consisting of L1 plus αCT domains and site 2, consisting of loops at the junction of FnIII-1 and FnIII-2 predicted to bind to the 'novel' hexamer face binding site of insulin. (wikipedia.org)
  • In addition to binding to the insulin receptor, IRS1 also binds to and transmits signals from the receptors of prolactin, growth hormone (GH), leptin, vascular endothelial growth factor (VEGF), tropomyosin receptor kinase B (TrkB), anaplastic lymphoma kinase (ALK), insulin like growth factor (IGF1), and integrins ( Vuori and Ruoslathi , 1994 Vuori K and Ruoslahti E (1994) Association of insulin receptor substrate-1 with integrins. (scielo.br)
  • The receptor for insulin is a large protein that binds to insulin and passes its message into the cell. (rcsb.org)
  • Two copies of the protein chains come together on the outside of the cell to form the receptor site that binds to insulin. (rcsb.org)
  • When insulin is not present, they are held in a constrained position, but when insulin binds, these constraints are released. (rcsb.org)
  • When insulin binds to the receptor, it is thought to cause a change in shape that is propagated inside the cell, activating the tyrosine kinases. (rcsb.org)
  • Surprisingly, insulin binds to the outer edge of the receptor, and typically only binds to one side of the symmetrical receptor. (rcsb.org)
  • Insulin binds outside the cell on the extracellular domain of its receptor and induces a structural change that is transmitted inside the cell to initiate the response. (mcgill.ca)
  • The GH molecule binds to its specific cell surface receptor (GHR), which dimerizes with another GHR molecule so that the single GH molecule is enveloped by 2 GHR molecules. (medscape.com)
  • All 22 exons of the insulin receptor gene were screened for mutations using denaturing gradient gel electrophoresis. (bmj.com)
  • The patient was homozygous for a point mutation in exon 2 of the insulin receptor gene which results in the substitution of methionine for isoleucine at codon 119. (bmj.com)
  • Met mutation in the insulin receptor gene, and are clinically affected with varying degrees of severity. (bmj.com)
  • In mammals, the insulin receptor (IR) gene has acquired an additional exon, exon 11. (scienceopen.com)
  • Given that, in Type II diabetes, successive generations of various cell types in the body ranging from muscles, tissues, blood, and organs are resistant to glucose uptake and exhibited reduced sensitivity to insulin, the underlying aetiology of Type II diabetes might involve the altered gene expression of stem cells in stem cell niches that adapted to a high glucose diet through an evolutionary conserved mechanism that aimed at homeostasis. (peerj.com)
  • Thus, successive generations of cells generated from the stem cell niche would exhibit an epigenetically controlled programme of gene expression that exhibited down regulation of genes for glucose transporters and insulin receptors. (peerj.com)
  • The above hypothesis helped explain why high sugar intake by the body could result in impaired sensitivity to insulin and reduced glucose uptake by cells, and more importantly, the widespread nature in which many cell types (principally muscle cells) are affected by a possible epigenetically controlled gene expression programme which hitherto appeared clinically irreversible. (peerj.com)
  • This study aims to identify insulin receptor substrate 1 (IRS-1) gene polymorphism Gly972Arg as the risk factor for ischemic stroke among Indonesian subjects. (biomedcentral.com)
  • This gene provides instructions for making a protein called an insulin receptor, which is found in many types of cells. (medlineplus.gov)
  • As a critical node for insulin/IGF signaling, insulin receptor substrate 1 (IRS-1) is essential for metabolic regulation. (nature.com)
  • Our findings delineate a mechanism in which LLPS of IRS-1-mediated signalosomes serves as an organizing center for insulin/IGF-1 signaling and implicate the role of aberrant IRS-1 LLPS in metabolic diseases. (nature.com)
  • Metabolic cell labeling followed by immunoprecipitation with monoclonal alpha and beta subunit-specific antibodies revealed the presence of hybrid rat/truncated human receptors, truncated transfected human receptors, and WT human IGF-I holotetramers. (jci.org)
  • Sesti G, Federici M, Hribal ML, Lauro D, Sbraccia P and Lauro R (2001) Defects of the insulin receptor substrate (IRS) system in human metabolic disorders. (scielo.br)
  • In addition to its normal spectrum of metabolic effects, insulin can act as a growth factor and has the ability to promote mitogenic activity. (scienceopen.com)
  • Conversely, IR-B is predominantly expressed in adult, well-differentiated tissues, including the liver, where it enhances the metabolic effects of insulin. (scienceopen.com)
  • Insulin-like growth factor 1 receptor is the primary target of the approved drug mecasermin, a recombinant form of endogenous IGF1. (guidetopharmacology.org)
  • Previous work has shown that the evolution of both insulin-like growth factor 1 (IGF1) and insulin shows an episode of accelerated change on the branch leading to New World monkeys (NWM). (figshare.com)
  • Analysis of receptor sequences from a range of primates and some non-primate mammals showed that accelerated evolution did indeed occur on this branch in the case of IGF1R and IR, but not for the similar insulin receptor-related receptor (IRRR) which does not bind insulin or IGF1. (figshare.com)
  • Overall the results suggest that adaptive coevolution of IGF1, insulin and their receptors and some IGFBPs occurred during the evolution of NWM. (figshare.com)
  • IRS-1 was the first of these to be identified as a 185 kDa protein that is detectable by immunoblot analysis in response to insulin stimulation [ 1 ]. (biomedcentral.com)
  • Hybrid receptors were studied in GC rat pituitary cells overexpressing either wild-type 950Tyr (WT) human insulin-like growth factor I (IGF-I) receptors or mutant human IGF-I receptors truncated at position 952 in the beta subunit transmembrane region (952STOP). (jci.org)
  • Thus mutant IGF-I receptors block ligand-mediated endogenous rat IGF-I signaling by functioning as a dominant negative forming nonfunctional human/rat hybrid receptors. (jci.org)
  • Finally, IR isoforms form heterodimers, IR-A/IR-B, and hybrid IR/IGF-IR receptors (HR-A and HR-B). The functional characteristics of such hybrid receptors and their role in physiology, in diabetes, and in malignant cells are not yet fully understood. (scienceopen.com)
  • These residues were concentrated in the N-terminal half of the IGF1R ectodomain but the C-terminal half of the IR ectodomain, which could have implications for the formation of hybrid receptors. (figshare.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)
  • Impairment of IRS-1 LLPS attenuated its positive effects on insulin/IGF-1 signaling. (nature.com)
  • We further identified that the 301-600 residues, as a self-association region (SAR), is essential to the formation of IRS-1 droplets and the transduction of insulin/IGF signaling. (nature.com)
  • Several signaling molecules have been identified as critical players in the regulation of insulin-induced IR activation. (mdpi.com)
  • The integration of GPCR and receptor tyrosine kinase (RTK) signaling, including IR upon ligand stimulation, is eloquently reviewed. (mdpi.com)
  • Mutant 952STOP cells were therefore completely devoid of biological signaling to GH despite the presence of endogenous rat IGF-I receptors. (jci.org)
  • Piceatannol, natural polyphenolic stilbene, inhibits adipogenesis via modulation of mitotic clonal expansion and insulin receptor-dependent insulin signaling in early phase of differentiation. (oregonstate.edu)
  • Furthermore, the piceatannol-suppressed mitotic clonal expansion was accompanied by reduced activation of the insulin-signaling pathway. (oregonstate.edu)
  • Taken together, our study reveals an anti-adipogenic function of piceatannol and highlights IR and its downstream insulin signaling as novel targets for piceatannol in the early phase of adipogenesis. (oregonstate.edu)
  • A novel dual GLP-1/GIP receptor agonist alleviates cognitive decline by re-sensitizing insulin signaling in the Alzheimer icv. (lancs.ac.uk)
  • Importantly, insulin signaling was re-sensitized as evidenced by a reduction of phospho-IRS1Ser1101 levels and phospho-AktSer473 up-regulation. (lancs.ac.uk)
  • In conclusion, the novel dual agonist DA-JC4 shows promise as a novel treatment for sporadic AD, and reactivating insulin signaling pathways may be a key mechanism that prevents disease progression in AD. (lancs.ac.uk)
  • Two hormones, insulin and glucagon, are at the center of this signaling system. (rcsb.org)
  • Problems with insulin signaling can impair the proper management of glucose levels in the blood, leading to the widespread disease diabetes mellitis . (rcsb.org)
  • Immunoglobulins against insulin-like growth factor 1 (IGF-1) receptors activate signaling in the orbital fibroblasts. (medscape.com)
  • IGF-1 stimulation enhanced IRS-1 phase separation which then recruited downstream effectors to form insulin/IGF signalosomes. (nature.com)
  • Similar results were observed with IRS-1-P, PI3K (p85 alpha), and Akt-P. In contrast, with IGF-IR and IRS-2-P, the basal levels (i.e. in the absence of insulin stimulation) were higher in cells cultured with palmitate. (unict.it)
  • Stimulation of a receptor in the brain that controls insulin responses has been shown to halt or diminish the neurodegeneration of Alzheimer's disease, providing evidence that the disease can be treated in its early stages, according to a study by researchers at Rhode Island Hospital and Brown Medical School. (news-medical.net)
  • Structural basis for recognition of phosphodiester-containing lysosomal enzymes by the cation-independent mannose 6-phosphate receptor. (nih.gov)
  • 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)
  • Insulin signalling controls access to blood glucose in body cells. (wikipedia.org)
  • However, treatment with common therapies such as insulin or insulinotrophic sulphonylureas (SU), while effective in reducing hyperglycaemia, may impose a greater risk of hypoglycaemia, as neither therapy is self-regulated by ambient blood glucose concentrations. (nih.gov)
  • Fasting blood glucose ( D ) and insulin ( E ) levels were measured ( n = 7-13), and a GTT ( F ) was performed. (jci.org)
  • When insulin falls, especially in those with high insulin sensitivity, body cells begin only to have access to lipids that do not require transport across the membrane. (wikipedia.org)
  • In HFD-fed mice, supplementation with the sialic acid precursor N-acetyl-D-mannosamine restored IgG sialylation and preserved insulin sensitivity without affecting weight gain. (jci.org)
  • 2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. (scielo.br)
  • 2005) Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. (scielo.br)
  • Marked accelerated evolution on this branch was also seen for some IGFBPs, but not the mannose 6-phosphate/IGF2 receptor or epidermal growth factor receptor. (figshare.com)
  • Insulin is an anabolic hormone that promotes glucose uptake, glycogenesis, lipogenesis, and protein synthesis of skeletal muscle and fat tissue through the tyrosine kinase receptor pathway. (medscape.com)
  • Thus, the mutant allele encodes a receptor that has a mutation in the putative insulin binding domain. (bmj.com)
  • Upon receptor dimerisation, after proteolytic cleavage into the α- and β-chains, the additional 12 amino acids remain present at the C-terminus of the α-chain (designated αCT) where they are predicted to influence receptor-ligand interaction. (wikipedia.org)
  • Despite their markedly increased ligand binding and prolonged receptor half-life, 952STOP transfectants failed to transduce the IGF-I signal to suppress growth hormone (GH). (jci.org)
  • For the most part, the residues that change on this branch could not be associated with specific functional aspects (ligand binding, receptor dimerization, glycosylation) and the physiological significance of this coevolution remains to be established. (figshare.com)
  • Out of 29 liver tissue sections examined, 14 had a low level of expression of insulin receptor type 1 by immunohistochemical studies. (who.int)
  • A standard insulin test is positive for endogenous insulin and exogenous insulin. (medscape.com)
  • However, it is still challenging to generate insulins that recapitulate the full spectrum of endogenous insulin action," explains Ünal Coskun, group leader at the Institute for Pancreatic Islet Research and Paul Langerhans Institute Dresden (IPI/PLID). (mcgill.ca)
  • Enables insulin-like growth factor binding activity and mannose binding activity. (nih.gov)
  • Orthologous to human IGF2R (insulin like growth factor 2 receptor). (nih.gov)
  • Human insulin-like growth factor I receptor function in pituitary cells is suppressed by a dominant negative mutant. (jci.org)
  • Insulin-like growth factor-1 receptor expression in pediatric tumors: " by RESUL KARAKUŞ, ESRA KARAKUŞ et al. (tubitak.gov.tr)
  • Background/aim: Insulin-like growth factor-1 receptor (IGF-1R) is a pivotal receptor tyrosine kinase involved in the cell cycle and malignant tumor transformation. (tubitak.gov.tr)
  • Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. (scienceopen.com)
  • The table contains 1 products whose active ingredient are classified under the same pharmacologic class Insulin-like Growth Factor-1 Receptor Inhibitor [EPC]. (ndclist.com)
  • Insulin-like growth factor-I receptor in metanephric development. (elsevierpure.com)
  • Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates essential processes of vascular maturation and stabilization. (lu.se)
  • Insulin-like growth factor I (IGF-I) is the effector of growth induced by growth hormone (GH). (medscape.com)
  • Our results indicated that insulin induces cell proliferation in a dose-dependent fashion in the LNCaP, C4-2, and P69 cell lines. (scienceopen.com)
  • Several of the structures of the insulin-binding portion of the molecule, including entry 3loh, were determined by attaching antibodies to the receptor and crystallizing the complex. (rcsb.org)
  • Ma Z, Gibson SL, Byrne MA, Zhang J, White MF and Shaw LM (2006) Suppression of insulin receptor substrate 1 (IRS-1) promotes mammary tumor metastasis. (scielo.br)
  • Over the past century, scientists have detailed the central role of insulin as a regulator of blood sugar and demonstrated its involvement in diabetes and other chronic conditions, including neurodegeneration and cancer. (mcgill.ca)
  • Further research is needed to fully dissect the molecular mechanisms underlying the biological actions of insulin in PCa. (scienceopen.com)
  • The biological actions of insulin are mediated by its receptor, which is localized to the cell surface. (mcgill.ca)
  • The research proposed in this grant will have a significant impact because when successfully completed it will fill key gaps in our understanding of the basic mechanism of insulin deficiency and type 2 diabetes in a large segment of the aging and androgen-deficient male population of the Veterans Healthcare system. (grantome.com)
  • You can use the Protein Feature View for insulin receptor at the RCSB PDB to determine which portion of the receptor is included in each PDB entry. (rcsb.org)
  • Type I diabetes is caused by problems with insulin: in some cases, the pancreatic cells that produce insulin are destroyed by autoimmunity, and in other cases insulin is mutated and inactive. (rcsb.org)
  • To better understand the role(s) of insulin or its lack and the resultant hyperglycemia in the etiology of these events, peripheral and neuronal (having 125 kDa and 115 kDa alpha subunits, respectively) insulin receptor subtype levels in the retinas of Streptozocin-induced diabetic rats were quantified. (diabetesjournals.org)
  • It was also demonstrated that PTPϵM suppressed insulin-induced glycogen synthesis and inhibited insulin-induced suppression of phosphoenol pyruvate carboxykinase (PEPCK) expression in primary hepatocytes. (bioone.org)
  • G protein-coupled receptors (GPCR) have recently been implicated in intracellular crosstalk pathways with IR. (mdpi.com)
  • Insulin receptor, with the extracellular portion at the top, intracellular portion at the bottom, and the cell membrane shown schematically in gray. (rcsb.org)
  • This study investigated in a pancreatic alpha-cell line the effects of chronic exposure to palmitate on the insulin and IGF-I receptor (IGF-IR) and intracellular insulin pathways. (unict.it)
  • Upon binding of insulin to the insulin receptor (IR), IRS1 is phosphorylated at several YXXM motifs creating docking sites for the binding of PI3Kp85, which activates AKT kinase. (scielo.br)
  • This analysis identified the insulin receptor substrate 1 and 2 (IRS1/2) as potential Pim substrates. (oncotarget.com)
  • The scientists hope that these details concerning insulin-receptor interactions will ultimately expand the current models of insulin binding to its receptor and inform new approaches to structure-based drug design. (mcgill.ca)
  • The up-regulated receptors retained their ability to undergo insulin-dependent autophosphorylation and, as such, did not appear functionally impaired. (diabetesjournals.org)
  • In this study, we examined the adipose expression of both TNF receptors (TNFR1 and TNFR2) in human obesity and demonstrated that obese female subjects express approximately twofold more TNFR2 mRNA in fat tissue and approximately sixfold more soluble TNFR2 in circulation relative to lean control subjects. (nih.gov)
  • This increase reflected a doubling of neuronal and a ∼20% decrease in peripheral insulin receptor subtypes, respectively. (diabetesjournals.org)
  • Insulin-treated diabetic rats had neuronal receptor levels equal to control values, at the same time having a further reduced number of peripheral insulin receptors relative to controls. (diabetesjournals.org)
  • Neuronal insulin receptors in WGA-purified cortical synaptosomal membranes also were increased in diabetic rats, with insulin treatment reducing this effect. (diabetesjournals.org)
  • These data suggest that the expression of neuronal insulin receptors in retina and brain and peripheral insulin receptors in the retina of diabetic rats is sensitive to levels of insulin/glucose in peripheral circulation. (diabetesjournals.org)
  • 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 key was to examine the outer part, or ectodomain, of the insulin receptor after saturating it with high concentrations of insulin," explains Theresia Gutmann, co-first author of the study from the Paul Langerhans Institute and the German Center for Diabetes Research. (mcgill.ca)
  • 125I-IGF-I binding was increased in both 950Tyr (WT) (14-fold) and truncated human IGF-I receptor (952STOP) stable transfectants (50-fold), when compared to untransfected cells that contained endogenous rat IGF-I receptors. (jci.org)
  • Defective IGF-I receptors may function therefore as dominant negative phenotypes which suppress normal receptor responses in pituitary cells. (jci.org)
  • We also demonstrated that insulin enabled LNCaP and C4-2 cells to progress through the cell cycle. (scienceopen.com)
  • IR-A is often aberrantly expressed in cancer cells, thus increasing their responsiveness to IGF-II and to insulin and explaining the cancer-promoting effect of hyperinsulinemia observed in obese and type 2 diabetic patients. (scienceopen.com)
  • cells that amplify GLP-1 receptor action. (grantome.com)
  • Although insulin is present in the bloodstream, the defective receptors make it less able to exert its effects on cells and tissues. (medlineplus.gov)
  • Acinar cells of the lacrimal glands express thyroid-stimulating hormone (TSH) receptors. (medscape.com)
  • At the beginning of this reaction, 1 molecule of 'phospho-IRS:activated insulin receptor' is present. (reactome.org)