Insulin receptor and IRS-1 co-immunoprecipitation with SOCS-3, and IKKα/β phosphorylation are increased in obese Zucker rat skeletal muscle.

Abstract Aims We evaluated if selected pro-inflammatory cytokines and/or the protein suppressor of cytokine signaling 3 (SOCS-3) could account for decreased insulin-stimulated phosphatidylinositol 3-kinase (PI3-K) activity in the skeletal muscle of the obese Zucker rat. Main methods Eight lean and eight obese Zucker rats ~ 4 weeks of age were obtained and allowed to feed ad libitum for 4 weeks before undergoing hind limb perfusion in the presence of 500 μU/ml insulin. Key findings Insulin-stimulated skeletal muscle PI3-K activity and 3-O-methylglucose transport rates were reduced (P  Significance Increased IKKα/β and JNK serine phosphorylation may contribute to increasing IRS-1 serine phosphorylation, while concurrent co-localization of SOCS-3 with both IR-β and IRS-1 may prevent IRS-1 from interacting with IR-β. These two mechanisms thusly may independently contribute to impairing insulin-stimulated PI3-K activation in the skeletal muscle of the obese Zucker rat.