A critical component of insulin action is the enzyme phosphoinositide (PI) 3-kinase. The major regulatory subunits of PI 3-kinase, p85alpha and its splice variants, are encoded by the Pik3r1 gene. Heterozygous disruption of Pik3r1 improves insulin signaling and glucose homeostasis in normal mice and mice made insulin-resistant by heterozygous deletion of the Insulin receptor and/or insulin rece...

Objective(s): Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex proteins are involved in membrane trafficking. The expression of isoforms of SNAP-23, syntaxin-4, and VAMP-2 is significantly done in skeletal muscles; they control GLUT4 trafficking. It is believed that type 2 diabetes could be caused by the modifications in the express...

Chronic hepatitis C virus (HCV) infection greatly increases the risk for type 2 diabetes and nonalcoholic steatohepatitis; however, the pathogenic mechanisms remain incompletely understood. Here we report gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) transcription and associated transcription factors are dramatically up-regulated in Huh.8 cells, which stably express an HCV subg...

objective(s): we aimed to examine association of gene expression of mor1 and glun1 at mrna level in the lumbosacral cord and midbrain with morphine tolerance in male wistar rats. materials and methods: analgesic effects of morphine administrated intraperitoneally at doses of 0.1, 1, 5 and 10 mg/kg were examined using a hot plate test in rats with and without a history of 15 days morphine (10 mg...

Background & aimsThe physiological regulation and contribution of the multiple phosphorylation sites insulin receptor substrate 1 (IRS1) to pathogenesis resistance is unknown. Our aims were map phosphorylated motifs IRS1 in skeletal muscle from people with normal glucose tolerance (NGT; n = 11) or type 2 diabetes mellitus (T2DM; 11).MethodsSkeletal biopsies obtained under fasted conditions duri...

Insulin resistance, reduced β-cell mass, and hyperglucagonemia are consistent features in type 2 diabetes mellitus (T2DM). We used pancreas and islets from humans with T2DM to examine the regulation of insulin signaling and cell-cycle control of islet cells. We observed reduced β-cell mass and increased α-cell mass in the Type 2 diabetic pancreas. Confocal microscopy, real-time PCR and western ...

CONTEXT Ovarian hormones modulate insulin sensitivity, but their exact role remains unclear. OBJECTIVE We tried to determine whether different doses of 17-beta-estradiol cause changes in the regulation of insulin receptor substrate (IRS-1) levels, and if so, the possible implications in insulin sensitivity. DESIGN Ovariectomized rats were treated with different doses of 17-beta-estradiol at...

A possible breakthrough in the treatment of diabetes was made with the discovery that a fungal natural product, demethylasterriquinone B1 (DAQ B1), is an orally active, small-molecule mimic of insulin. Subsequent work has shown that the glucose-lowering effects of DAQ B1 are not accompanied by enhanced vascular proliferation, which is a side effect of chronic insulin administration that can lea...

Recruitment of activated immune cells into white adipose tissue (WAT) is linked to the development of insulin resistance and obesity, but the mechanism behind this is unclear. Here, we demonstrate that Y1 receptor signaling in immune cells controls inflammation and insulin resistance in obesity. Selective deletion of Y1 receptors in the hematopoietic compartment of mice leads to insulin resista...