Database for Annotation, Visualization and Integrated Discovery 2.1
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insulin receptor(INSR) insulin receptor(INSR) Related Genes Homo sapiens
CYTOBAND 19p13.3-p13.2,
GENERIF_SUMMARY Chiral mutagenesis of insulin's hidden receptor-binding surface, Role of insulin receptor dimerization domains in ligand binding, cooperativity, and modulation by anti-receptor antibodies, cross-sectional data suggest a role of physiological concentration of fasting plasma adiponectin in the regulation of skeletal muscle IR tyrosine phosphorylation, an arginine to cysteine(252) mutation from a patient with severe insulin resistance inhibits receptor internalisation but preserves signalling events, Sam68 associates with the SH3 domains of Grb2 recruiting GAP to the Grb2-SOS complex in insulin receptor signaling, Transactivation of INSR by calcitrol, Insulin-IGF1 hybrid receptors have different tissue-specific responses based on their isoforms, insulin receptor may play a role in the regulation of ovarian cancer cell growth, alanine-scanning mutagenesis of the insulin receptor A and B isoforms has identified several new side chains contributing to insulin binding and indicates that the energetic contributions of certain side chains differ in each, A C/T single nucleotide polymorphism at the tyrosine kinase domain of the insulin receptor gene is associated with polycystic ovary syndrome., inhibition of insulin-stimulated insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase/Akt signaling pathway by disrupting the association of IRS-1/IRS-2 with the insulin receptor, Donohue's syndrome (leprechaunism) was found to be homozygous for an in-frame trinucleotide deletion within the insulin receptor gene resulting in the deletion of valine 335., The IR may serve as a cellular substrate for both protein tyrosine phosphatase forms TC48 and TC45. Differentially localized variants of TCPTP may dephosphorylate the IR and downregulate insulin-induced signaling in vivo., Cornea and conjunctiva express insulin receptor in cytoplasm of epithelium., dynamics of the interaction between this receptor and protein tyrosine-phosphatase 1B in living cells, This protein is activated both by human and Caenorhabditis elegans insulin., HMGI-Y physically interacts with Sp1 and C/EBP beta and facilitates the binding of both factors to the insulin receptor promoter, the human insulin receptor gene promoter has a vitamin D response element, Interaction of filamin A with the insulin receptor alters insulin-dependent activation of the mitogen-activated protein kinase pathway., High glucose impairs insulin secretion by affecting insulin receptor expression, splicing, and signaling in islets of Langerhans., the presence of a free heavy chain IgG in the circulation from spinal cord-injured subjects blocked insulin receptor binding sites and also blocked the prostacyclin receptor interaction in platelets; insulin-induced NO synthesis was markedly impaired., Fibroblasts from leprechaunism patients with mutant insulin receptors have altered gene expression., INSR-A, the predominant isoform in fetal tissues and malignant cells, binds with a high affinity insulin and IGF-II, which differentially regulate gene expression., None of the polymorphisms in INSR or IRS1 was associated with metabolic syndrome findings., Human micro- and macrovascular endothelial cells express more IGF-I receptor than insulin receptor., Insulin receptor splicing alteration is associated with myotonic dystrophy type 2, Linkage analysis and mutation screening revealed missense mutation (Arg1174Gln) in tyrosine kinase domain of insulin receptor gene that cosegregated with disease phenotype., Data show that in adipocytes the insulin receptor is localized to caveolae,and that part of insulin receptor substrate 1 (IRS1), the immediate downstream signal mediator, colocalizes with the insulin receptor in the plasma membrane and caveolae., The C and D domains of IGF-II promote higher affinity binding to the IR-A than the equivalent domains of IGF-I., The exon-definition model explains alternative splicing of exon 11 in the insulin receptor gene in-vivo but not in-vitro., Mrna elevated in polycystic ovary syndrome. Granulosa cell insulin receptor heterogeneity, together with adiposity-dependent intrafollicular insulin availability, is novel mechanism by which insulin may affect granulosa cell function within follicle., Increased systolic and diastolic blood pressure, heart rate, plasma insulin, and decreased erythrocyte insulin receptors preexist in healthy offspring of patients with essential hypertension., Molecular modeling of the IRK domain indicated that the ATP-binding site becomes distorted after releasing the nucleotide unless the IRK domain is oxidatively derivatized at Cys1245., the G972R naturally occurring polymorphism of IRS-1 not only reduces phosphorylation of the substrate but allows IRS-1 to act as an inhibitor of the insulin receptor kinase, producing global insulin resistance, Our findings suggest, for the first time, that AMPK activation could reduce the expression of insulin receptor, at least in part, by a down-regulation of the transcriptional level, and this effect may be liver specific., This study suggests an association between the affinity of insulin receptors and number of IGF-1 receptors with placental and/or fetal growth., This study provides evidence to suggest cross down-regulation of leptin and insulin receptors at both receptor and downstream signalling levels., analysis of insulin receptor functional insulin binding epitopes, Transcriptional repression of the human insulin receptor gene mediated by estrogen receptor beta in U-937 cells., Polymorphism in exon 17 of insulin receptor leads to increased risk of insulin resistance in women with polycystic ovary syndrome., activation of T-cells with development of insulin receptors in hyperglycemic conditions may serve as a mechanism for control of glucose entry into these cells and protect them against glucose toxicity, Receptor binding studies indicate that alpha-PGG binds to the IR and affects the binding between insulin and IR by reducing the maximum binding of insulin to IR without significantly altering the binding affinity of insulin to IR., 3-phosphoinositide-dependent protein kinase 1 (PDK1) directly binds to the insulin receptor, followed by PDK-1 activation and insulin metabolic effects., In conclusion, this study detected no INSR mutations in affected members of a chromosome 19 linked migraine pedigree. Hence, migraine linkage to this chromosomal region may involve other candidate genes., Results led to a conclusion that the novel T/C SNP at codon Cys1008 of INSR is associated with decreased insulin sensitivity in Chinese women with polycystic ovary syndrome., Impaired insulin clearance in part rescues in vivo insulin signalling in muscle in these carriers of a mutant INSR by increasing insulin action on the non-mutated insulin receptors, C/T polymorphism in exon 17 of the INSR gene is not associated with susceptibility of polycystic ovary syndrome in a Korean population., These data strongly suggest that these domains contain an insulin binding site., Data show that hybrid receptors formed by insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant., coordinated physical and functional interactions between hnRNP H, CUG-BP1 and MBNL1 dictate IR splicing in normal and DM1 myoblasts, Differential expression of insulin receptor, IGF-IR, and IGF-I in adhesion fibroblasts may contribute to pathogenesis of fibrosis in diabetic patients., These data suggest a role for the IR, but not the IGF-IR, in KSHV-induced transformation of vascular ECs., 6 sites of mucin-type O-glycosylation were found at residues T744, T749, S757, S758, T759, & T763 in a 20-residue segment lacking secondary structure, followed by residues 765-770, the mAb 18-44 epitope., APS-mediated ubiquitination of the IR induced enhancement of the IR internalization, but did not affect the IR degradation., High levels of insulin receptor expression in early stage breast cancers is independently and significantly associated with more favorable clinical outcomes., Alpha 1,3-fucosyltransferase-VII regulates the signaling molecules of the insulin receptor pathway, Data show that IGF-1 acts through insulin receptors to preferentially activate insulin receptor substrate 2 (IRS-2) , but not IRS-1., the regulation of glucose uptake, proliferation, and type I collagen production by visfatin in human osteoblasts involves IR phosphorylation, the same signal-transduction pathway used by insulin, Insulin uptake & dose-response experiments toward activation of downstream signal transduction molecules demonstrated that presence of intact hIR-JM domain which harbors the NPEY motif is essential for Shc phosphorylation but not for IRS-1 phosphorylation, PPAR-gamma, insulin receptor with its signaling pathways, and StAR protein constitute a novel human ovarian regulatory system with complex interactions among its components, Since HMGA1 regulates IR promoter activity, expression of IR gene was impaired causing reduction of IR on cell surface and that compromises with insulin sensitivity., provide evidence for a mechanism of adiponectin resistance and corroborate the notion that adiponectin potentiates hepatic insulin sensitivity, These results demonstrate that the InsR regulates choriocarcinoma cell invasion through activation by IGF-II., increased soluble insulin receptor ectodomain level appears to be a more rapid glycemic marker than A1C or glycoalbumin, CALR and Hsp90 stabilize INSR., These data indicate that IR is a tyrosine kinase receptor, which undergoes PS/gamma-secretase-dependent processing., Among the analyzed single nucleotide polymorphisms (SNPs), +176477 C>T, a novel SNP in the INSR gene, was associated with the pathogenesis of polycystic ovary syndrome in a Korean population., Insulin receptor serine kinase, PSD-95, and the Kv1.3 potassium channel co-localize to regulate membrane excitability and synaptic transmission at critical locations in the olfactory bulb., physiologically relevant levels of naturally secreted Abeta interfere with insulin receptor function in hippocampal neurons and prevent the rapid activation of specific kinases required for long term potentiation, Carrying the variant allele of the IRS1 Gly972Arg SNP further decreased the risk for colorectal cancer among the INSR-603G allele carriers., despite binding equipotency, insulin, and S597 initiate different signaling and biological responses through the same insulin receptor isoform, compositions of the glycans were determined, Partial DNA sequences of defective insulin receptor gene in two sisters with elevatetd plasma adiponectin and leptin levels., 24 insulin analogues and four IGF analogues were expressed and analyzed to explore the role of amino acid differences in the A- and B-domains between insulin and the IGFs in binding affinity for the insulin receptor, Polymorphism in postinsulin receptor signaling pathway is not associated with polycystic ovary syndrome., differential gene expression of insulin receptor in cells, by insulin and S597, Corosolic acid may exert its antidiabetic effects by enhancing insulin receptor phosphorylation., The first replication study for the reported association of the insulin receptor gene (INSR) with migraine with aura was perfoermed., reduced adipose tissue lipoprotein lipase expression, being significantly correlated with the decrease in insulin and prolactin, suggests a role of hyperinsulinemia and hyperprolactinemia in inducing and sustaining obesity., autoimmunity to insulin receptors may be causal in insulin resistance syndrome especially for females with ovarian hyperandrogenism, and that IR-ab may be found in insulin resistance syndrome besides those previously defined by the type B phenotype, Competitive equilibrium binding assays revealed significantly reduced specific binding to the insulin, IGF-I, and IGF-II and their receptors in both the anterior cingulate and vermis of alcoholic human brains., IR and IGF-IR are present in human preadipocytes and adipocytes. Differentiation is characterized by an increased IR/IGF-IR ratio., Microvascular endothelial cells are sensitive to IGF-I but resistant to insulin due to a preponderance of IGF-I receptors and sequestration of insulin receptors into insulin/IGF-I hybrid receptors., The role of the IGF/insulin receptors in cervical cancer cell lines with different Human papillomavirus (HPV) status, SiHa (HPV positive), and C33a (HPV negative), was assessed., Crystal structures for inhibitor-kinase complexes in which the inhibitor has different binding orientations and hydrogen-bonding patterns with extracellular-signal regulated kinase 2 and insulin receptor tyrosine kinase, are reported., observations document the presence of insulin receptors on primary human prostate cancers, testosterone and 17beta-estradiol can directly enhance insulin receptor mRNA expression, insulin binding and glucose oxidation in Chang liver cells and thereby glucose metabolism, the PTPase activity in patients with insulin receptor gene mutation and severe insulin resistance may differ from that in ordinary type 2 diabetes, Insulin interacts in trans with two receptor binding sites to generate high-affinity interactions., SRp20, SF2/ASF, and CUG-BP1 act antagonistically to regulate IR alternative splicing in vivo and that the relative ratios of SRp20 and SF2/ASF to CUG-BP1 in different cells determine the degree of exon inclusion., An analysis of some of these sequences shows that TCR from both human diabetics and NOD mice mimic insulin, glucagon, the insulin receptor, and the glucagon receptor., Two sisters with heterozygous mutations in the insulin receptor gene associated with mild glucose intolerance., Val(43), Phe(28), and Val(14) (equivalent to site 1) are critical to IGF-1R and IR binding, whereas mutation to alanine of Gln(18) affects only IGF-1R and not IR, R1174 of the IR gene may be a candidate locus for hyperinsulinaemic hypoglycaemia., Significant association of C/T polymorphism at His1058 of INSR with PCOS in the lean rather than obese Indian women., IR-beta levels were unchanged from the resting levels after both exercise trials in deltoid, Results show that leptin and insulin receptors are strongly up-regulated in placentas of hydatidiform mole and abortion, and suggest that they may be candidates for the endocrine control of human pregnancy., RNA for the insulin-independent IR-A isoform was significantly increased and appeared related to the fibre-type composition in the majority of the myotonic dystrophy cases examined., dysfunctions of brain insulin and IGF-1 receptors contribute to Abeta aggregation and subsequent synaptic loss, A thermodynamic study of ligand binding to the first three domains of the human insulin receptor., cellular levels of IR are down-regulated in obesity as well as in obese fat tissues., Data show that ICT-EIA for sIRalpha may be useful as a good marker for evaluating diabetes risk., At least partially overlapping signaling pathways are essential for the development of normal rod photoreceptors in IR transgenic mice., the 5'-UTR of the mRNA encoding human insulin receptor contains a functional internal ribosome entry segment., The lack of similar mutation records in literature and genetic data banks may suggest a geographic pattern for these INSR gene variants in our population., Likely digenic cause of insulin resistance and growth deficiency resulting from the combined heterozygous disruption of INSR and CHN2, implicating CHN2 for the first time as a key element of proximal insulin signaling in vivo., LRP1 mediates anti-apoptotic function in neurons by regulating insulin receptor and the Akt survival pathway, insulin action on platelet function in platelets expressing hybrid Insulin/IGF-1 receptors, Taken together, these findings suggest that the structural movements within the receptor upon ligand binding are small and are possibly limited to local rotation of domains., this study provides the first demonstration that serum deprivation may not be sufficient, and G0/G1 synchronization may be required to obtain optimal responsiveness of hIR-overexpressing cell lines., The association of insulin receptor (IotaNSR) and insulin receptor substrates (IRSs) polymorphisms with the risk of developing polycystic ovary syndrome, was investigated., The autophosphorylation of insulin receptors decreases in polycystic ovary syndrome patients., Studies show that BMS-754807 is a reversible inhibitor of the insulin-like growth factor 1 receptor/insulin receptor and increases poly ADP ribose polymerase and Caspase 3 cleavage, findings indicate that TNF-alpha induces a loss of sensitivity to stimulation by IGF-I, through reducing amount of IGF-I/insulin hybrid receptor and the stimulation of HR tyrosine kinase activity by IGF-I., Stduies indicate that cGMP-dependent protein kinase I modulates the RhoA-ROCK pathway and insulin receptor signaling to elicit BAT differentiation and stimulate thermogenesis., a nonsense mutation causing premature termination after amino acid 331 in the alpha subunit of the insulin receptor was identified in Japanese diabetes patients., analysis of a tandem hormone-binding element in the insulin receptor, IR and IGF1R act as identical portals to the regulation of gene expression, with differences between insulin and IGF-1 effects due to a modulation of the amplitude of the signal created by the specific ligand-receptor interaction, Study revealed that insulin receptor endocytosis is necessary for two identified feedback mechanisms involving mass and information transfer., Association of insulin receptor genetic variants with polycystic ovary syndrome in european women., Case Report, insulin binds the IR in two distinct phases, hybrid insulin/IGF-I receptor (hybrid-R), which is present in endometrial carcinoma cells, may have an important role in mediating IGF- and insulin-induced cell growth and in preventing apoptosis., our findings suggest that increased expression of the IR is a consequence of epileptic seizures and a cause of intractable epilepsy, These results suggest that the PKD family is involved in the transcriptional regulation of the InsR gene., these results identify a novel aspect in the crosstalk between insulin receptor and GPCR signaling systems in pancreatic cancer cells., rs3745551 located in 3'-UTR of the INSR is associated with insulin resistant phenotype, Our data suggest that IR isoforms and IGF-I receptor play a role in the biology of follicular thyroid precursors, Studies indicate that insulin, IGF-1, TrkA, and TrkC receptors as trophic and as dependence receptors., Studies provide a clear biological rationale to test anti-IGF-IR/InsR therapy in combination with chemotherapy in patients with TNBC., INSR H1085H C>T polymorphism seems to be associated with prostate cancer risk., A pathway-based tagging SNP approach allowed us to identify novel INSR SNPs associated with PCOS, one of which confirmed association in a large replication cohort., The p.Ile119Met INSR appears to have arisen around the Horn of Africa, and should be sought first in severely insulin resistant patients with ancestry from this region, The findings provide direct evidence for a functional interaction between CB1R and IR signaling involved in the regulation of beta-cell proliferation., in breast cancer cells, IGF-2 activates ER-alpha and ER-beta, and modulates their translocation to nucleus, membrane organelles and mitochondria; IGF-2 actions are mediated by IGF-1R and insulin receptor, PTP1B plays a crucial role in the control of the activity of the IR precursor during its biosynthesis. In addition, this new substrate-trapping mutant may be a valuable tool for the identification of new PTP1B substrates., insulin and IGF-I activate their cognate receptors and IGF-I also activates naturally occuring IGF-I/insulin hybrid receptors (HR) IGF-II activates insulin receptor, IGF-I receptor and HR, IGF1 might inhibit insulinogenic differentiation of HEAC, whereas IGF2 enhances differentiation, and enhancement of IGF2 appears to be mediated via IR, Partial methylation of the INSR gene occurs in the endometria of polycystic ovary syndrome patients, but this study does not provide a strong evidence supporting the relationship between insulin resistance and INSR gene methylation in women with PCOS., No significant evidence of association or linkage was found in the four tested markers, indicating that our family samples did not support susceptibility of the INSR gene to PCOS., These findings indicate that IR-A activation by IGF-II elicits a unique signaling pathway that may play a distinct role in physiology and in disease., Thus the results of the present study provide a structural insight into the mechanism of the regulation of insulin receptor binding by exon 11, The A1028V mutaion is associated with a decrease in expression of the insulin receptor, potentially accounting for its loss of function., A kinome-wide siRNA screen showed that the insulin receptor is required for growth of MCF-7 cells resistant to long-term estrogen deprivation., higher INSR-A and lower INSR-B contribute to higher proliferation and lower metabolic response. Thus, differential expression of INSR isoforms represents a potential biological link between breast cancer and diabetes., Biallelic c.433 C>T (p.R118C) mutation of INSR causes significant damage to insulin binding and insulin-mediated signal transduction, the mRNA levels of IR-B were significantly decreased in tumors. The IR-A, Met stimulates hepatocyte glucose uptake through crosstalk with insulin receptor., The placental lectins reduced the binding of insulin and to IR in a dose-dependent manner., complexes could mediate crosstalk among STATs, estrogen receptor beta (ERbeta), and AP-1 regulating the ERbeta-mediated transcriptional repression of the hIR gene and insulin resistance in U-937 cells, These data point to a functional interaction between hnRNP F and SRSF1 as a mutant that eliminates SRSF1 binding to exon 11, or a SRSF1 knockdown, which prevents the stimulatory effect of hnRNP F over expression., This study has therefore lead to a greater understanding of the mechanisms of IGF-II binding and activation of the IGF-1R and IR-A., These data provide evidence that human beta- and alpha-cells can enter the cell-cycle, but proliferation of beta-cells in type 2 diabetes mellitus fails due to G1-to-S phase arrest secondary to defective insulin signaling., Data support the concept for dual IGF-1R/IR targeting in hepatocellular carcinoma (HCC)., Despite tenfold elevated fasting insulin and marked insulin resistance in Arg1174Gln insulin receptor carriers, the levels of total adiponectin, leptin, IGFBP1 and IGFBP2 are similar to those observed in controls., Data suggest that INSR, leptin receptor (LEPR), and carnitine palmitoyltransferase 1A (CPT1A) mRNA levels are higher in blood cells/blood from overweight children compared with normal weight children; INSR and CPT1A are increased only in males., co-association of LDLR with IR and their dissociation by insulin may be an important part of the regulatory mechanism of the normal physiological receptor function in a biological system., insulin evoked significant IR-A internalization, a process modestly affected by IGF-II, Studies indicate that PTP1B and TCPTP act together in vitro and in vivo to regulate insulin receptor (IR) signaling and glucose homeostasis., both IGF1R and IR were N-linked glyosylated in figitumumab-sensitive cells, the fine regulation of the expression of different isoforms of insulin receptor(IR) during osteogenic differentiation confirms the important role played by IR in bone homeostasis, In this study, we investigated 31 SNPs across the INSR gene and identified a novel SNP of rs17254521 in intron 2 which is associated with hypertension., Insulin promotes the proliferation of Reh cells. High expression levels of IR and IGF-IR may be closely related with the growth of leukemia cells., Extracellular nucleotides inhibit insulin receptor signaling, stimulate autophagy and control lipoprotein secretion., This study provides evidence that IR secretion is increased in HIV-seropositive women, and increased IR secretion is associated with cognitive impairment in these women., genetic association studies in Chinese populations, Mutation of the insulin receptor gene in a preterm infant is associated with Donohue syndrome and heart failure, The "T" allele of the His1085His polymorphism in the INSR gene shows significant protection against diabetes. This study gains importance because there are no data available to date on the role of INSR variants in T2D in the Indian population., Human cardiac microvascular endothelial cells express more IGF1Rs than IRs, and mainly react to IGF1 due to the predominance of IGF1Rs and insulin/IGF1 hybrid receptors., The nuclear localization and function of the IGF-1R/INSR (Hybrid-R) and the role of IGF-1/IGF-1R and Hybrid-R signaling in the human corneal epithelium., Data from normally cycling young women suggest that expression of INSR (and glucose transporter 1) in endometrium is higher in luteal/secretory phase (compared to follicular phase) and is localized to stromal cells (compared to epithelial cells)., Data suggest that only a fraction of circulating insulin-like activity is due to insulin itself; serum IGF-I and IGF-II may substantially contribute to insulin receptor signaling., Group B streptococci-induced formation of polymorphonuclear leukocyte function is specifically downmodulated by insulin via insulin receptor-mediated induction of phosphatidylinositol 3-kinase., study reports that expression of the insulin receptor in kidney is altered during diabetes; a strong expression in proximal and distal tubules from renal cortex, and a significant reduction in type 2 diabetic patients was detected, Studies indicate that insulin receptor (IR) and IGF Type 1 Receptor (IGFR) have been identified as important partners of Grb10/14 and SH2B1/B2 adaptors., Insulin receptor isoform A to B ratio was significantly higher in cancer as well as in tumor adjacent benign prostate tissue compared to purely benign prostates, presentation of the first view of the interaction of insulin with its primary binding site on the insulin receptor, on the basis of four crystal structures of insulin bound to truncated insulin receptor constructs, INSR rs1366600, ACSL1 rs2292899 and FABP2 rs11724758 could influence the susceptibility to type 2 diabetes in Chinese Han population, most likely through their effects on the specific miRNA-binding sites., Using all-atom structural models this work endeavored to understand the conformational reorganization of insulin on binding to its receptor in the presence of a recently resolved critical tandem hormone-binding element, the CT-peptide., Results of this study demonstrated the dependence of INSR and related to insulin receptor signaling gene expressions in U87 glioma cells on ERN1 enzyme function indicating its participation in the regulation of metabolic and proliferative processes via endoplasmic reticulum stress which is important component of tumor growth and metabolic diseases., Indinavir and nelfinavir inhibit proximal insulin receptor signaling and salicylate abrogates inhibition, the LRP6(R611C) mutation diminishes TCF7L2-dependent transcription of the IR while it increases the stability of IGFR and enhances mTORC1 activity., A mechanism responsible for the generation of mitogenic IR-A via a novel interplay between IR and EGFR pathways in hepatocellular carcinoma., Data suggest that the distinct fiber type involvement in DM1 and DM2 muscle tissues would not be related to qualitative differences in the expression of insulin receptor gene (INSR)., this study did not find an association between VNTR INS, C/T INSR and Gly792Arg IRS-1 polymorphism and susceptibility to polycystic ovary syndrome or insulin resistance in Croatian women with PCOS, Data indicate that insulin receptor isoformA (IR-A) mRNA was differentially expressed in four endometrial carcinoma cell lines., LMBD1 plays an imperative role in mediating and regulating the endocytosis of the IR., The impact of insulin on different cell types in the intestinal epithelium might differ depending on relative IR-B IR-A expression levels., INSR (rs1052371) was not associated with colorectal cancer risk in an Iranian cohort., Protective effects of breastfeeding are reflected in higher expression levels of SLC27A2, FASN, PPARalpha and INSR in blood cells., A novel heterozygous mutation of the insulin receptor gene (INSR) was identified in this family with with type A insulin resistance syndrome, Findings show that in vitro model could be useful for determining the molecular mechanism underlying insulin receptor (IR) cleavage., REVIEW, Grb14-insulin receptor interaction is regulated in part by GSK-3 activity., study concluded that the His 1058 C/T polymorphism at the tyrosine kinase domain of the INSR gene had a relationship to the pathogenesis of lean polycystic ovary syndrome patients in a Japanese population, Insulin-induced phosphorylation of the insulin receptor is dependent on Neu1 sialidase activity., Data suggest that insulin/insulin receptor signaling plays pivotal roles in differentiation, function, and survival of osteoblasts; osteoblastic insulin signaling is also required for energy metabolism. [REVIEW], Different insulin receptor family expression levels were measured in six cancer cell lines., CUL7, OBSL1 and CCDC8 modulate the alternative splicing of the INSR, Overexpression of INSR increased cell proliferation, colony formation, migration, invasion and resistance to apoptosis in prostate cancer., These results show that IR can be activated through a pathway that bypasses its canonical ligand-binding domain., Data indicate that changes in tyrosine phosphorylation of insulin receptor (InsR) are associated with insulin resistance (IR) in patients with gestational diabetes mellitus (GDM), Data indicate that engineered ubiquitin ligase is an effective therapeutic strategy for the treatment of the cancers with co-expressed insulin receptor/insulin-like growth factor receptor (IR/IGF-1R)., MET, HER3, IGF1R, and INSR pathways activation represent novel mechanism underlying lapatinib unresponsiveness in HER2+ gastric cancer. Combination strategy may be recommended in treating patients with HER2+ gastric cancer with these pathways activation, Our work provides evidence supporting a link between IGFIR and IR isoform expression levels and colorectal adenoma risk., Determining the amount of phosphorylated insulin receptor could thus represent a novel prognostic/predictive tool in colorectal adenocarcinoma patients., studied whether the reversal of gestational diabetes mellitus effects on transport by insulin depends on restoration of insulin receptor-A expression, Results suggest INSR CT or TT genotype carriers have an increased risk for developing refractory temporal lobe epilepsy, Data suggest that PBEF/NAMPT (nicotinamide phosphoribosyltransferase) inhibits insulin/insulin receptor beta (IR) signaling via PBEF/NAMPT-dependent promotion of IR translocation into non-raft domains of lung epithelial cell membrane., found significant associations between other variants of the INSR gene and colorectal cancer risk, It is reported here that both splice variants of insulin/IGF1 receptor hybrids are activated by IGF1 with >20-fold higher potency than insulin., The rs2059807 could be a promising candidate SNP that might be involved in the development of Polycystic ovary syndrome., Insulin receptor (IR) signaling and endocytosis are regulated by AMPK,enzyme of purine de novo synthesis pathway ATIC,putative tyrosine phosphatase PTPLAD1. IR/PTPLAD1/ATIC/AMPK form a complex within the plasma membrane and Golgi/endosome.ATIC deletion increases AMPK-Thr172 phosphorylation.Both ATIC and PTPLAD1 affect IR tyrosine phosphorylation.With AICAR, they regulate insulin mediated translocation of Glut2 in HEK 293., Data revitalizes the role of the INSR isoforms in the pathogenesis of type 2 diabetes mellitus, and suggests that an abrogated INSRB, A disease entity of adult-onset hyperinsulinemic hypoglycemia syndrome associated with mutations in INSR gene., The insulin receptor and IGF1 receptor kinase domains are functional dimers in the activated state., rs2059806 of INSR was associated with both type 2 diabetes mellitus and type 2 diabetic nephropathy, while rs7212142 of mTOR was associated with type 2 diabetic nephropathy but not type 2 diabetes mellitus in a Chinese Han population., only Ptprj was co-expressed with the IR in major insulin target tissues , Three SNPs of the INSR, rs2059807, s8109559 and rs919275, were significantly associated with obesity-related cancers (p value < 0.02) with the most significantly associated SNP being rs2059807 (p value = 0.008)., The INSR rs2059806 SNP is associated with small for gestational age pregnancies., Non-small cell lung cancer cell survival crucially depends on functional insulin receptors, novel nonsense mutations are associated with reduced expression of the mature INSR beta-subunit, which was most likely due to impaired proreceptor processing, INSR (rs1799816) polymorphism conferred risk towards T2D in Brahmins., Study provides evidence that IR, irrespective of isoform type, mediates primary resistance to IGF-IR-targeted therapy and can be used as a potential biomarker for patient selection., Down-regulation of IR and IGF1R, achieved by insulin + fructose and monoclonal antibody treatments, results in decreased downstream signaling., The results demonstrate an increased IR-A, remarkable therapeutic window observed for BI 885578 is achieved by virtue of the distinctive pharmacokinetic properties of the compound capitalizing on the physiologic mechanism of glucose homeostasis and differential levels of IGF1R and INSR expression, Low-oxygen tension can modify the IGF-1 or IGF-2 signaling via the IGF-1R and IR in placental mesenchymal stem cells., Given the limited number of patients treated with KW-2450 in our study, it is not possible to make a meaningful comparison of efficacy with other IGF-1R/IR dual kinases inhibitors, Data indicate that a highly specific qRT-PCR assay to quantify levels of the insulin-like growth factor receptor and insulin receptor isoforms (IR-A, IR-B, and IGF-1R) on the same scale to provide a critical diagnostic and predictive tool., results indicate a significant correlation between T132903C and C109869T single nucleotide polymorphisms in the insulin receptor and solute carrier family 6 member 14 amino acid transporter (SLC6A14) genes with idiopathic infertility in Persian males,
OMIM_DISEASE Leprechaunism, Rabson-Mendenhall syndrome, Hyperinsulinemic hypoglycemia, familial, 5, Diabetes mellitus, insulin-resistant, with acanthosis nigricans,
SP_COMMENT catalytic activity:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate., disease:Defects in INSR are the cause of familial hyperinsulinemic hypoglycemia 5 (HHF5) [MIM:609968]. Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels., disease:Defects in INSR are the cause of insulin resistance (Ins resistance) [MIM:125853]., disease:Defects in INSR are the cause of insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:610549]. This syndrome is characterized by the association of severe insulin resistance (manifested by marked hyperinsulinemia and a failure to respond to exogenous insulin) with the skin lesion acanthosis nigricans and ovarian hyperandrogenism in adolescent female subjects. Women frequently present with hirsutism, acne, amenorrhea or oligomenorrhea, and virilization. This syndrome is different from the type B that has been demonstrated to be secondary to the presence of circulating autoantibodies against the insulin receptor., disease:Defects in INSR are the cause of leprechaunism [MIM:246200]; also known as Donohue syndrome. Leprechaunism represents the most severe form of insulin resistance syndrome, characterized by intrauterine and postnatal growth retardation and death in early infancy. Inheritance is autosomal recessive., disease:Defects in INSR are the cause of Rabson-Mendenhall syndrome [MIM:262190]; also known as Mendenhall syndrome. It is a severe insulin resistance syndrome characterized by insulin-resistant diabetes mellitus with pineal hyperplasia and somatic abnormalities. Typical features include coarse, senile-appearing facies, dental and skin abnormalities, abdominal distension, and phallic enlargement. Inheritance is autosomal recessive., disease:Defects in INSR may be associated with noninsulin-dependent diabetes mellitus (NIDDM) [MIM:125853]; also known as diabetes mellitus type 2., enzyme regulation:Autophosphorylation activates the kinase activity., function:This receptor binds insulin and has a tyrosine-protein kinase activity. Isoform Short has a higher affinity for insulin. Mediates the metabolic functions of insulin. Binding to insulin stimulates association of the receptor with downstream mediators including IRS1 and phosphatidylinositol 3'-kinase (PI3K). Can activate PI3K either directly by binding to the p85 regulatory subunit, or indirectly via IRS1. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin., online information:Insulin receptor entry, PTM:After being transported from the endoplasmic reticulum to the Golgi apparatus, the single glycosylated precursor is further glycosylated and then cleaved, followed by its transport to the plasma membrane., PTM:Autophosphorylated on tyrosine residues in response to insulin., PTM:Phosphorylation of Tyr-999 is required for IRS1- and SHC1-binding., similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily., similarity:Contains 1 protein kinase domain., similarity:Contains 3 fibronectin type-III domains., subunit:Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chains carry the kinase domain. Interacts with SORBS1 but dissociates from it following insulin stimulation. Binds SH2B2. Interacts with the PTB/PID domains of IRS1 and SHC1 in vitro when autophosphorylated on tyrosine residues. The sequences surrounding the phosphorylated NPXY motif contribute differentially to either IRS1 or SHC1 recognition. Interacts with the SH2 domains of the 85 kDa regulatory subunit of PI3K (PIK3R1) in vitro, when autophosphorylated on tyrosine residues. Interacts with SOCS7. Forms a hybrid receptor with IGF1R, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R., tissue specificity:Found as a hybrid receptor with IGF1R in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibrobasts, spleen and placenta (at protein level). Isoform Long and isoform Short are expressed in the peripheral nerve, kidney, liver, striated muscle, fibroblasts and skin. Isoform Short is expressed also in the spleen and lymphoblasts.,