Glomerular-specific protein kinase C-β-induced insulin receptor substrate-1 dysfunction and insulin resistance in rat models of diabetes and obesity.

ABSTRACT: Insulin resistance has been associated with the progression of chronic kidney disease in both diabetes and obesity. In order to determine the cellular mechanisms contributing to this, we characterized insulin signaling in renal tubules and glomeruli during diabetic and insulin-resistant states using streptozotocin-diabetic and Zucker fatty-insulin-resistant rats. Compared with nondiabetic and Zucker lean rats, the insulin-induced phosphorylation of insulin receptor substrate-1 (IRS1), Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3α were selectively inhibited in the glomeruli but not in the renal tubules of both respective models. Protein, but not mRNA levels of IRS1, was decreased only in the glomeruli of streptozotocin-diabetic rats likely due to increased ubiquiti

SUBMITTER: Mima A 

PROVIDER: S-EPMC3612886 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature