The insulin receptor
is expressed in the heart and regulates cardiac cell activity though the PI3K-AKT pathway.
Increased hepatic levels of the insulin receptor
inhibitor, PC-1/NPP1, induce insulin resistance and glucose intolerance.
Zueco et al., "Insulin receptor
substrate-4 signaling in quiescent rat hepatocytes and in regenerating rat liver," Hepatology, vol.
Abbreviations ADN: Adiponectin ADNR: Adiponectin receptor ALT: Alanine aminotransferase AMPK: 5-AMP-activated protein kinase AUC: Area under the curve HOMA-IR: The homeostasis model assessment of insulin resistance IKK: Inhibitory-[kappa]B kinase pIKK: Phosphorylated inhibitory-[kappa]B kinase protein NF: Nuclear factor pNF: Phosphorylated nuclear factor IRS: Insulin receptor
substrate tIRS: Total insulin receptor
substrate LETO: Long-Evans Tokushima Otsuka NEFA: Nonesterified fatty acids OGTT: Oral glucose tolerance test OLETF: Otsuka Long-Evans Tokushima Fatty PPAR: Peroxisome proliferator-activated receptor TZD: Thiazolidinedione WAT: White adipose tissue.
These mediators activate the serine/threonine kinase cascade leading to serine phosphorylation of the insulin receptor
and insulin receptor
substrates (IRS-1/2), causing a decrease in PI3K activation [14, 69-73] (Figure 1).
Primary antibodies used included Epac1, IL-1[beta], Rap 1 (Abcam, Cambridge, MA), phosphorylated p38 MAPK, total p38 MAPK, phosphorylated JNK, total JNK, phosphorylated insulin receptor
(Tyr 1150/1151), total insulin receptor
, phosphorylated Akt (Ser473), total Akt, Akt2, phosphorylated IRS-1 (Ser307), total IRS-1 (Cell Signaling Corp, Danvers, MA), and beta-actin (Santa Cruz, CA).
Donohue syndrome is a condition in which binding of insulin to insulin receptors
(INSR) and signalization of insulin is disrupted.
Conclusion: Hepatitis C virus has no effect on insulin receptor
substrate 2 content thus indicating absence of hepatic insulin resistance in patients with HCV infection.
Transcriptional activation of the human insulin receptor
gene by 1,25-dihydroxyvitamin D(3).
The c-Jun NH2-terminal kinase promotes insulin resistance during association with insulin receptor
substrate-1 and phosphorylation of Ser307.
Cardiac fibroblasts, indeed, express the insulin receptor
(IR) , the insulin growth factor-like 1 and its receptor (IGF-1/IGF-1R) , and the insulin-responsive glucose transporter (Glut4) .
High insulin concentration in insulin resistance stimulates lipogenesis through the activation of sterol regulatory element-binding protein 1 (SREBP-1c) , which inhibits insulin receptor
substrate 2 (IRS-2) mediated insulin signaling .