AICAR Administration Causes an Apparent Enhancement of Muscle and Liver Insulin Action in Insulin-Resistant High-Fat-Fed Rats

• DOI: 10.2337/diabetes.51.10.2886
• Publication Date: 2007-03-06T19:04:22Z
• Authors: Miguel A. Iglesias; Ji-Ming Ye; Georgia Frangioud...; Asish K. Saha; Eva Tomas; Neil B. Ruderman; Gregory J. Cooney; Edward W. Kraegen
• Keywords: Carbohydrate Metabolism

Exercise improves insulin sensitivity. As AMP-activated protein kinase (AMPK) plays an important role in muscle metabolism during exercise, we investigated the effects of AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) on action insulin-resistant high-fat-fed (HF) rats. Rats received a subcutaneous injection 250 mg/kg AICAR (HF-AIC) or saline (HF-Con). The next day, euglycemic-hyperinsulinemic clamp studies were performed. Glucose infusion rate was enhanced (50%) HF-AIC compared with HF-Con Insulin-stimulated glucose uptake improved white but not red quadriceps, whereas glycogen synthesis both and quadriceps rats also showed increased suppressibility hepatic output (HGO). AICAR-induced responses liver accompanied by reduced malonyl-CoA content. Clamp HGO correlated closely triglyceride content (r = 0.67, P < 0.01). Thus, single dose leads to apparent enhancement whole-body, muscle, HF that extends beyond expected time activation. Whether altered tissue lipid mediates remains be determined. Follow-up suggest at least some post-AICAR insulin-enhancing occur normal Independent this, results pharmacological activation may have potential treating states type 2 diabetes.