The Effects Of Exenatide On Insulin Sensitivity And Glucose-Lipid Metabolism In High Fat-Fed Rats

Objective To investgate the effects of Exenatide on isletβ-cell function, insulin sensitivity and glucose-lipid metabolism in insulin resistant rats induced by high-fat-diet.Methods High fat-fed rats were treated by exenatide for 6 weeks. The insulin sensiyivity, isletβ-cell function and glucose lipid metabolism in awake rats were evaluated by intravenous glucose tolerance test (IVGTT), insulin tolerance test (ITT) and hyperinsulinemic-euglycemic clamp technique combined with 3-[3H] glucose as a tracer. In addition, plasma adiponectin levels were measured by ELISA.Results Plasma free fatty acids (FFA), triglyceride (TG), total cholesterol (TC) levels were significantly reduced in high fat-fed rats after exenatide treatment (all P<0.01). In these rats exenatide also improved IVGTT and ITT, and increased the levels of insulin secretion, especially when a high dose was given. In addition, plasma adiponectin levels also significantly increased in group with high dose exenatide (HFH, P<0.01). During the clamp steady-state, there were a significant increase in plasma FFA and insulin and significant decrease in glucose infusion rate (GIR), glucose disposal rate (GRd) in high-fat group (HF) compared to control group (NC, all P<0.01). The suppressive effect of insulin on hepatic glucose production (HGP) was significantly blunted (only 26%) in HF group. In HFH group, plasma insulin and FFA levels were significantly decreased (all P<0.01), GIR and GRd significantly increased (all P<0.01), and HGP was suppressed by 72%.Conclusion Exenatide pretreatment ameliorates high-fat induced insulin resistance by promotingβ-cell insulin secretion, elevating adiponectin level, and improving glucose-lipid metabolism.