Physical exercise enhances hepatic insulin signaling and inhibits phosphoenolpyruvate carboxykinase activity in diabetes-prone Psammomys obesus.
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 < .02). G6Pase activity was higher in the CH and EH groups compared with the CL group (261 +/- 54 nmol/min/mg protein, 251 +/- 34 nmol/min/mg protein, and 75 +/- 32 nmol/min/mg protein, respectively) (P < .01). After insulin administration in the fast state, tyrosine phosphorylation of IR and association of IRS-2 with PI3-K were higher in the EH and CL groups than in the CH group. We conclude that exercise improves in vivo hepatic insulin sensitivity in diabetes-prone Psammomys-obesus.
Heled
Yuval
Y
Heller Institute of Medical Research and Pediatric Division, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Shapiro
Yair
Y
Shani
Yoav
Y
Moran
Daniel S
DS
Langzam
Lea
L
Barash
Varda
V
Sampson
Sanford R
SR
Meyerovitch
Joseph
J
D000818:Animals; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005849:Gerbillinae; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D007328:Insulin / Q000502:physiology*; D008099:Liver / Q000502:physiology*; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D007328:Insulin; D011506:Proteins; D005952:Glucose-6-Phosphatase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)