Phosphatidylinositol-3-kinase is involved in the antihyperglycemic effect induced by resveratrol in streptozotocin-induced diabetic rats.
Resveratrol, a polyphenolic substance found in grape skin, is proposed to account in part for the protective effect of red wine in the cardiovascular system. The aim of the present study is to investigate the action and possible mechanisms of resveratrol-produced regulation of plasma glucose in normal and diabetic rats including the animal model of streptozotocin (STZ)-induced and nicotinamide-STZ-induced (NA-STZ), and insulin-resistant diabetic rats. Resveratrol (p.o.) produced a hypoglycemic effect in a dose-dependent manner in normal and diabetic rats, and the insulin level was increased following resveratrol treatment in normal and NA-STZ diabetic rats. In insulin-deficient STZ-diabetic rats, resveratrol significantly lowered the plasma glucose 90 min after oral treatment, and the hypoglycemic effect was abolished by phosphatidyl-3-kinase (PI3K) inhibitors (LY294002 and wortmannin) which also inhibited resveratrol-induced Akt phosphorylation in soleus muscle of STZ-diabetic rats. The change in the protein expression level of glucose transporter subtype 4 (GLUT4) in the soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of STZ-diabetic rats treated with resveratrol (3 mg/kg, p.o.) for 7 days was examined. Resveratrol normalized hepatic PEPCK expression and increased GLUT4 expression in the soleus muscle of STZ-diabetic rats. The results indicate that the mechanisms contributing to the hypoglycemic effect of resveratrol include insulin-dependent and insulin-independent pathway, and PI3K-Akt-signaling was involved in the latter mechanism to enhance glucose uptake in skeletal muscle.
Chi
Tzong-Cherng
TC
Institute of Pharmacology, College of Medicine, National Taiwan University, No 1, Sec 1, Jen-Ai Rd, Taipei, Taiwan.
Chen
Win-Pin
WP
Chi
Tsung-Li
TL
Kuo
Tzong-Fu
TF
Lee
Shoei-Sheng
SS
Cheng
Juei-Tang
JT
Su
Ming-Jai
MJ
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects*; D002262:Carboxy-Lyases / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D027843:Vitis / Q000737:chemistry; D000077191:Wortmannin
D000730:Androstadienes; D000975:Antioxidants; D001786:Blood Glucose; D002262:Carboxy-Lyases; D002867:Chromones; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol; D013267:Stilbenes; D000077191:Wortmannin; C495694:Slc2a4 protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one