The Mechanism Study Of Exendin-4 Amelioration Insulin Resistance

Objective: To investigate the effects of Exendin-4 on insulin sensitivity and adipocytokine.Methods: Rats were divided randomly into standard (NC group, n=10 ) or high fat (n=20) chow groups for 10 weeks. After 10 weeks, 10 rats fed by high-fat diet (HE group) were were given Exendin-4 at a dose of 2μg/kg and 10 rats (HF group) were given saline. The insulin sensitivity were evaluated by intravenous insulin tolerance test (IVITT) and insulin signal, visfatin and adiponectin expression levels were also observed in these rats.Results:1) In HF rats plasma cholesterol (TC), triglyeride(TG) and free fatty acid (FFA) levels were significantly increased and insulin- sensitiving index was significantly decreased, compared with NC group. After exendin-4 treatment, TC, TG and FFA levels were significantly decreased and IR was obviously ameliorated. 2) The protein tyrosine phosphorylation of IRS-1 in muscle and adipose tissue was significantly decreased in HF rats ( P<0.05). There was no different between HE and NC groups in the levels of IRS-1 tyrosine phosphorylation. 3) There was no different among three groups in visfatin mRNA expression of muscle and adipose tissue. But plasma visfatin levels in HF and HE groups were significantly reduced compared with NC group(P﹤0.05). The adiponectin mRNA expression of adipose tissue was highest in HE group, and lowest in HF. And plasma adiponectin level was significantly increased in HE group compared with NC group(P<0.01).Conclusion: Chronic Exendin-4 treatment improved insulin sensitivity accompanied by a decrease in plasma FFA levels. The mechanism of amelioration insulin resistance may relate to tyrosine phosphorylation of IRS-1 and adipokine.