The study of mechanism for exendin-4(exenatide)improving insulin resistance / 中国糖尿病杂志

ABSTRACT

Objective To investigate the effects of exendin-4 (exenatide) on insulin sensitivity and adipocytokine in high-fat-fed rats. Methods Rats were divided randomly into normal-chow group (NC), high-fat group (HF) and high-fat+exendin treated group (HE). HE rats were given exenatide (2 μg/kg) twice daily for 6 wk. The insulin sensitivity was evaluated by intravenous insulin tolerance test (IVITT). Insulin-stimulated changes in insulin signal transduction, visfatin and adiponectin mRNA expressions as well as their plasma levels were also observed in these rats. Results Plasma free fatty acids (FFA), triglyceride (TG), total cholesterol (TC) levels were significantly reduced after exenatide treatment (in HE rats all P<0.01). And IVITT parameters were also improved in these rats. Insulin-stimulated IRS-1 tyrosine phosphorylation was slightly increased in exenatide-treated rats as compared with HF rats (P<0.05). In addition,plasma visfatin level was significantly reduced in HF and HE groups as compared with controls (P<0.05 and P<0.01). The adiponectin mRNA expression in adipose tissues and circulating adiponectin level were significantly elevated in exenatide-treated rats as compared with untreated rats and controls (P<0.01). Conclusions Chronic exenatide treatment improves insulin resistance in high-fat-fed rats, and the changes of IRS-1 tyrosine phosphorylation and adiponectin may be related to the role of exenatide in elevating insulin sensitivity