• ligand
  • Receptor activation occurs through ligand binding, which facilitates receptor dimerization and autophosphorylation of specific tyrosine residues in the cytoplasmic portion. (abcam.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)
  • The binding of ligand to the α-chains of the IR ectodomain induces structural changes within the receptor leading to autophosphorylation of various tyrosine residues within the intracellular TK domain of the β-chain. (wikipedia.org)
  • Although the precise binding mechanism of IR and its ligand has not yet been elucidated structurally, as identified using a systems biology approach, biologically relevant prediction of the IR-ligand kinetics (insulin/IGF-I) has been identified in the context of the currently available IR ectodomain structure. (wikipedia.org)
  • As a result, interaction of a receptor with its specific ligand which is located outside of the cell causes changes to the receptor part which is inside the cell. (wikipedia.org)
  • Following receptor activation by the ligand, several steps can sequentially ensue. (wikipedia.org)
  • In canonical notch signaling, ligand proteins bind to the extracellular domain of the notch receptor and induce the cleavage and release of the intracellular domain into the cytoplasm. (wikipedia.org)
  • pathway
  • kinase pathway in a cell line by treating with insulin (1 uM). (bio.net)
  • 7 , 8 The dual role of metformin in inhibiting both the activation of the IR/IGF-1R by lowering systemic insulin levels, and interfering with signaling downstream of these receptors by inhibiting mTORC1 signaling, highlights the IR/IGF-1R pathway as a key mediator of both the response of tumor cells to the metabolic microenvironment and the regulation of tumor cell metabolism. (pubmedcentralcanada.ca)
  • Stud- ies are proposed to assess the mechanisms of GPR120 signaling to decipher precisely how signals from this receptor intersect with the inflammatory pathway. (labome.org)
  • Lyn has also been implicated to have a role in the insulin signaling pathway. (wikipedia.org)
  • resistance
  • In some patients, insulin resistance results from a decrease in the number of insulin receptors on the cell surface. (diabetesjournals.org)
  • Impaired insertion in the plasma membrane also causes insulin resistance. (diabetesjournals.org)
  • In two sisters (patients A-5 and A-8) with type A extreme insulin resistance, there is an 80-90% decrease in the number of insulin receptors expressed on the surface of their cells. (diabetesjournals.org)
  • 3 However, numerous microenvironmental insults can inhibit the function of the IR/IGF-1R signaling pathways and cause insulin resistance, hyperglycemia and hyperinsulinemia. (pubmedcentralcanada.ca)
  • DESCRIPTION (provided by applicant): Obesity is the dominant cause of acquired insulin resistance and it is the epidemic of obesity in the United States which is driving the dramatically increasing incidence of Type 2 diabetes. (labome.org)
  • Our previous work has shown that genetically disabling macrophage inflamma- tory pathways in knockout mice protects animals from obesity and high fat diet induced insulin resistance, lead- ing to the idea that the tissue macrophage can be an orchestrating or initiating cell type underlying this inflam- mation-induced insulin resistance. (labome.org)
  • These cells are highly proinflammatory releasing large amounts of tissue cytokines which can cause insulin resistance through paracrine mechanisms. (labome.org)
  • An improved understanding of the biology of these cells should provide new mechanistic insights into the etiology of inflammation/insulin resistance. (labome.org)
  • These results should identify relevant mechanisms where-by modification of inflammatory pathways in macrophages and in insulin target cells regu- lates systemic insulin resistance. (labome.org)
  • This knowledge should lead to a better understanding of insulin resistance in Type 2 diabetes and could potentially lead to novel therapeutic approaches. (labome.org)
  • PUBLIC HEALTH RELEVANCE: Obesity is the dominant cause of acquired insulin resistance and the epidemic of obesity in the United States is driving the dramatic increase in incidence of Type 2 diabetes. (labome.org)
  • Chronic low-grade tissue inflammation is a major cause of insulin resistance and the studies in this application will identify new mechanisms underlying the regulation of inflammation and how inflammation causes insulin resistance. (labome.org)
  • An increased expression level of this protein was found in the insulin-responsive tissue of obese, insulin-resistant individuals, and may contribute to the pathogenesis of insulin resistance. (wikipedia.org)
  • A much milder form of the disease, in which there is some insulin resistance but normal growth and subcutaneous fat distribution, is also known. (wikipedia.org)
  • allele
  • In the allele derived from the father, there is a nonsense mutation at codon 672 that truncates the insulin receptor by deleting the COOH-terminal of the α-subunit and the entirβ-subunit. (diabetesjournals.org)
  • A heterozygous individual (i.e. one who is a carrier for the disease, having only one normal allele for the insulin receptor) will not be affected. (wikipedia.org)
  • In one case, it was found (by culturing pancreatic cells) that the receptor produced by the mutant allele is only about 15% as effective as the normal receptor. (wikipedia.org)
  • Binding
  • An insulin-resistant patient has been identified in whose insulin receptors there is a defect in tyrosine kinase activity due to a mutation that substitutes valine for glycine-1008, the third glycine in the conserved Gly-X-Gly-X-X-Gly motif in the ATP-binding domain of the β-subunit of the insulin receptor. (diabetesjournals.org)
  • 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)
  • Many of the problems associated with Donohue syndrome may be due to the insulin receptor binding the insulin-like growth factor, regulating the growth of the embryo, in addition to its well-known role in the regulation of blood sugar. (wikipedia.org)
  • precursor
  • This mutation, identified in two sisters from a consanguineous pedigree, inhibits the cleavage of the receptor precursor into separate subunits. (diabetesjournals.org)
  • After removal of the precursor signal peptide, the insulin receptor precursor is post-translationally cleaved into two chains (alpha and beta) that are covalently linked. (genetex.com)
  • subunit
  • Both sisters, whose parents are first cousins, are homozygous for a point mutation in which valine is substituted for phenylalanine at position 382 in the a-subunit of the insulin receptor. (diabetesjournals.org)
  • induces
  • This addition of phosphate induces what are called "cell signaling" cascades - and the usual result of activation of the IGF-1 receptor is survival and proliferation in mitosis-competent cells, and growth (hypertrophy) in tissues such as skeletal muscle and cardiac muscle. (wikipedia.org)
  • mutation
  • As the mutation causing the disorder affects insulin receptor function, those with the disease are also insulin resistant, with hypoglycemia and profound hyperinsulinemia (very high levels of insulin in the blood) Another feature of the disease is that the subcutaneous adipose tissue is markedly diminished, which contributes to the unusual appearance of affected individuals. (wikipedia.org)