Physical exercise enhances hepatic insulin signaling and inhibits phosphoenolpyruvate carboxykinase activity in diabetes-prone Psammomys obesus.

Abstract We have shown that physical exercise enhances insulin sensitivity of skeletal muscle in diabetes-prone Psammomys-obesus . In this study, we examined the effect of physical exercise on the liver of these animals. Three groups of animals were exposed to a 4-week protocol; high-energy diet (CH), high-energy diet and exercising (EH), and low-energy diet (CL). Different groups were studied either in a fed state or after an overnight fast, 30 minutes after intraperitoneal (IP) injection of 1 U insulin. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) activity was measured. Insulin signaling response was examined after insulin injection in the fast state by analyzing tyrosine phosphorylation of insulin receptor (IR) and the association between insulin receptor substrate-1 (IRS-1) and IRS-2 with phosphatidylinositol 3 kinase (PI3-K). After 4 weeks, none of the EH animals became diabetic, whereas all the CH animals became diabetic. PEPCK activity in the fed state was higher in the CH group compared with the CL and EH groups (480 ± 28 nmol/min/mg protein, 280 ± 30 nmol/min/mg protein, and 208 ± 13 nmol/min/mg protein, respectively) ( P P Psammomys-obesus .