Disease relevance of Insr

• Despite the clear memory-correlated alterations in IR signaling pathways, insulin deficits in experimental diabetes mellitus (DM) rats induced by intraperitoneal injections of streptozotocin resulted in only minor memory impairments [1].
• Intramuscular triglyceride (IMTG) deposition in skeletal muscle is associated with obesity and type 2 diabetes (T2DM) and is thought to be related to insulin resistance (IR) [2].
• In contrast, metabolic effects such as insulin-induced glucose utilization in adipocytes, and insulin-induced amino acid utilization in Fao hepatoma cells were inhibited (70-80%) in cells overexpressing the JM but not the CT domains of IR [3].
• Monkeys (Macaca mulatta) were CR for a mean of 10.4 years, preventing weight gain and IR [2].
• Methylatropine further accelerated tachycardia and diminished the enhanced BRS in the IR group [4].

Psychiatry related information on Insr

• After long-term memory consolidation following a water maze learning experience, gene expression of IR showed an up-regulation in the CA1, but a down-regulation in the CA3 region [1].
• The insulin-resistant brain state is related to late-onset sporadic Alzheimer's disease, and alterations in the insulin receptor (IR) and its downstream phosphatidylinositol-3 kinase signalling pathway have been found in human brain [5].
• They suggested that diets high in fat and energy and low in complex carbohydrates and a sedentary life-style lead to IR and that the associated hyperinsulinemia, hypertriglyceridemia, and glycemia lead to increased CRC risk through the growth-promoting effect of insulin or the increased availability of energy [6].

High impact information on Insr

• Insulin receptor phosphorylation may not be a prerequisite for acute insulin action [7].
• Insulin receptor antiserum and plant lectins mimic the direct effects of insulin on nuclear envelope phosphorylation [8].
• SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2 and the insulin receptor [9].
• Systemic inhibition of nitric oxide synthase (NOS) with NG-monomethyl-L-arginine (L-NMMA) causes acute insulin resistance (IR), but the mechanism is unknown [10].
• We tested whether L-NMMA-induced IR occurs via NOS blockade in the central nervous system (CNS) [10].

Chemical compound and disease context of Insr

• The HR and BRS in reflex tachycardia were significantly increased in the IR and IS groups, but the BRS in reflex bradycardia was not different among all rats [4].
• Insulin receptor tyrosine kinase activity and substrate 1 (IRS-1) expression in human myometrium and leiomyoma [11].
• To better understand the mechanisms underlying these effects, the abilities of insulin and vanadate to affect IR gene expression have been comparatively examined in Fao hepatoma cells, an insulin-responsive cell line [12].
• This study examines the relationship between insulin resistance (IR) induced by fructose feeding (FF) and susceptibility to myocardial ischemia/reperfusion injury (MI/R) [13].
• In summary, the development of IR and hypertension is governed not by gender per se but by the interactions of specific sex hormones such as estrogen and testosterone [14].

Biological context of Insr

• Sennidin A did not induce tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), but induced phosphorylation of Akt and glucose transporter 4 (GLUT4) translocation [15].
• The current study sought to verify whether glucosamine (GlcN)-induced insulin resistance is associated with impaired insulin receptor (IR) autophosphorylation [16].
• AIM: To examine the effects of Astragalus polysaccharide (APS), a component of an aqueous extract of Astragalus membranaceus roots, on protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin-receptor (IR) signal transduction, and its potential role in the amelioration of insulin resistance [17].
• In situ hybridization was used to investigate the cellular distribution of IDE mRNA and to compare it with insulin receptor (IR) and IGF-I receptor (IGFR) gene expression in serial thin sections from a variety of tissues in embryonic and adult rats [18].
• A current view is that endocytosis of the insulin receptor (IR) kinase results in its rapid deactivation and sorting of the IR back to the cell surface or to late endocytic compartments [19].

Anatomical context of Insr

• Here we investigated changes in long-term memory-associated expression of the IR and downstream molecules in the rat hippocampus [1].
• IR autophosphorylation was measured in skeletal muscle after in vivo insulin stimulation (ie, during clamp) by Western blot and then retested after subsequent in vitro 0.1 to 100 nmol/L insulin stimulation (by enzyme-linked immunosorbent assay [ELISA]) [16].
• Our results suggest that in rat adipocytes, sennidin A stimulates glucose incorporation in the phosphatidylinositol 3-kinase (PI3K)- and Akt-dependent, but in the IR/IRS1-independent manner [15].
• It was found that insulin could bind with IR at the membrane of the neurons, and IR distribute not only on the somas, but also on the neurites [20].
• We conclude that in vivo endothelial cells rapidly take up and concentrate insulin relative to plasma and muscle interstitium and that IGF-IR, like IR, may mediate insulin transit through endothelial cells in a process involving caveolae [21].

Associations of Insr with chemical compounds

• In rat INS-1E beta cells, only Pklr expression was suppressed by low glucose as in islets, while Insr and Insrr were suppressed by high and increased by low glucose levels [22].
• Our results suggest that the IR and/or IGF-IR signaling pathway may be involved in the mechanism of action of HCB [23].
• Sections of fed liver were incubated with fluorescein-tagged anti-GLUT2 or Texas Red-tagged anti-IR [24].
• Our results demonstrated that the increase in PTP1B expression and/or association with IR in MSG animals may contribute to the impaired insulin signaling mainly in liver and muscle [25].
• AII increased the serine phosphorylation of both the IR beta-subunit and IRS-1 [26].

Physical interactions of Insr

• HepG2 cells were firstly selected to be the model for methodological study, the results showed that insulin could bind with IR at the membrane of the studied cells after incubated 1 minute with the cells [20].

Enzymatic interactions of Insr

• Analysis of the catalytic activity of partially purified rat adipocyte PTP-alpha and LAR and recombinant PTP-1B showed that all three PTPases dephosphorylate IR [27].

Regulatory relationships of Insr

• These results demonstrate that TNF-alpha participates in obesity-related systemic insulin resistance by inhibiting the IR tyrosine kinase in the two tissues mainly responsible for insulin-stimulated glucose uptake: muscle and fat [28].
• Insulin caused an immediate stimulation of Src and induced its physical association with both IR and PKCdelta [29].
• Insulin receptor tyrosine kinase activity solubilized from hind limb muscle of control and streptozocin-induced diabetic (STZ-D) rats (2-3 wk) was studied with the substrates histone H2B and poly glutamic acid-tyrosine (glu-tyr) (4:1) [30].

Other interactions of Insr

• Furthermore, beta cell expression of IGF-I receptor (Igf1r) and insulin receptor (Insr) is mandatory for several steps of insulin secretion [22].
• Insulin receptor and IRS-1 appeared to be translocated to the nucleus in a time dependent manner by insulin whereas Akt levels remained unchanged by insulin treatment [31].
• It is rarely reported the direct imaging on the binding of insulin with IR of neurons by microcopy system in live cells [20].
• Protein tyrosine phosphatase 1B (PTP1B) acts as a physiological negative regulator of insulin signaling by dephosphorylating the activated insulin receptor (IR) [32].
• There was some but less overlap of IR or IGF-IR or FITC-insulin with caveolin-1 [21].

Analytical, diagnostic and therapeutic context of Insr

• METHODS: We performed chronic hyperinsulinaemic-euglycaemic clamps and delineated, by western blotting, an IR/IRSs/phosphatidylinositol 3-kinase(PI[3]K)/Akt pathway in insulin-responsive tissues of hyperinsulinaemic rats [33].
• The association of IR and GLUT2 was further assessed by confocal microscopy [24].
• The expression and localization of the insulin receptor (IR) was examined in rat dorsal root ganglia (DRG) and spinal cord using Western blotting, in situ hybridization and immunocytochemistry [34].
• Here, using two-hybrid assays and in vitro assays of protein interaction, we show that the epsilon isoform of 14-3-3 interacts with the insulin-like growth factor I receptor (IGFIR) and with insulin receptor substrate I (IRS-1), but not with the insulin receptor (IR) [35].
• After rats were fed a protein-free diet (PF) or a 12% casein diet for 1 week, their IR and IRS-1 states were analyzed by immunoblotting using various antibodies [36].

References