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目的探讨Exenatide对高脂诱导胰岛素抵抗(insulin resistance,IR)大鼠胰岛素敏感性及血浆脂联素、瘦素水平的影响。方法将69只清洁级健康雄性(SD)大鼠分为对照组(NC组,n=22),高脂组(HF组,n=23),Exenatide治疗组(HE组,n=24)。高脂诱导胰岛素抵抗大鼠给予Exenatide10周后,采用扩展胰岛素钳夹技术测定机体胰岛素敏感性和糖脂代谢,并观察血浆脂联素、瘦素水平的变化。结果高脂诱导IR大鼠经Exenatide处理(HE组)后,Lee’s指数、空腹血浆游离脂肪酸(FFA)、甘油三酯(TG)、总胆固醇酯(TC)、低密度脂蛋白(LDL)明显降低(P<0.01),高密度脂蛋白(HDL)明显升高(P<0.01)。同时,HE组血浆脂联素水平明显升高(P<0.01),瘦素水平明显降低(P<0.01)。在钳夹稳态时,高脂组(HF)与对照组(NC)相比,血浆FFA、胰岛素(INS)水平均明显升高(P<0.01),葡萄糖输注率(GIR)、葡萄糖清除率(GRd)明显降低(P<0.01),且胰岛素对肝糖输出(HGP)的抑制作用明显障碍(仅抑制16%)。经Exenatide处理后,血浆FFA、INS水平则明显降低(P<0.01),GRd、GIR明显升高(P<0.01),胰岛素对HGP的抑制作用明显增强(抑制67%)。结论 Exenatide处理可能通过下调血浆瘦素水平和上调血浆脂联素水平,改善糖脂代谢而使机体胰岛素敏感性增加。
Objective To investigate the effects of Exenatide on insulin sensitivity and plasma adiponectin and leptin levels in insulin resistance (IR) -induced rats. Methods Ninety-nine healthy male SD rats were divided into control group (NC group, n = 22), hyperlipidemia group (HF group, n = 23) and Exenatide treatment group (n = 24). After 10 weeks of Exenatide administration in rats with high fat-induced insulin resistance, insulin sensitivity and glucose and lipid metabolism were measured by extended insulin clamp and the changes of plasma adiponectin and leptin levels were observed. Results The Lee’s index, fasting plasma free fatty acid (FFA), triglyceride (TG), total cholesterol ester (TC), and low density lipoprotein (LDL) were significantly decreased after Exenatide treatment (P <0.01), and high density lipoprotein (HDL) increased significantly (P <0.01). At the same time, plasma adiponectin level was significantly increased (P <0.01) and leptin level was significantly lower in HE group (P <0.01). Compared with the control group (NC), the levels of plasma FFA and insulin (INS) were significantly increased (P <0.01), the glucose infusion rate (GIR), glucose clearance (GRd) was significantly lower (P <0.01), and insulin inhibition of hepatic glycogen output (HGP) was significantly impaired (only 16% inhibition). After Exenatide treatment, plasma FFA and INS levels were significantly decreased (P <0.01), GRd and GIR were significantly increased (P <0.01), insulin inhibition of HGP was significantly enhanced (67% inhibition). Conclusion Exenatide treatment may increase the body’s insulin sensitivity by down-regulating plasma leptin levels and up-regulating plasma adiponectin levels and improving glucose and lipid metabolism.