胰高血糖素样肽-1对肥胖2型糖尿病大鼠胰岛素敏感性的改善作用

Effects of glucagon-like peptide-1 improving insulin sensitivity in obese type 2 diabetic rats

目的探讨胰高血糖素样肽(GLP)-1对肥胖2型糖尿病(T2DM)大鼠胰岛素敏感性的改善作用及机制。方法 12只6周龄雄性SD大鼠随机分为T2DM组、T2DM+GLP-1组及正常对照组(NC组)。T2DM组及T2DM+GLP-1组高脂喂养、NC组普食喂养4 w,给予T2DM组及T2DM+GLP-1组链脲佐菌素(STZ)30 mg/kg腹腔注射建立T2DM模型。受试大鼠进行高胰岛素-正葡萄糖钳夹实验。T2DM+GLP-1组大鼠在钳夹实验前30 min开始持续输注GLP-1,检测钳夹实验120 min葡萄糖输注率及0、30、60、90、120 min血清胰岛素浓度。Wester印迹法测定大鼠腓肠肌丝氨酸/苏氨酸激酶(Akt)磷酸化水平。结果与NC组比较,T2DM组钳夹实验120 min葡萄糖输注率降低(P<0.05),骨骼肌Akt磷酸化水平下降;与T2DM组比较,T2DM+GLP-1组钳夹实验120 min葡萄糖输注率增加(P<0.05),骨骼肌Akt磷酸化水平升高;各组间胰岛素浓度变化无差异(P>0.05)。结论 GLP-1可以增加平静状态T2DM大鼠葡萄糖摄取,改善骨骼肌的胰岛素敏感性,这一改善作用不依赖于胰岛素浓度的增加。

Objective To investigate the mechanism of Glucagon-like peptide(GLP)-1acted with insulin sensitivity in obese type 2 diabetic(T2DM)rats.Methods Twelve SD rats were randomized into T2DM,T2DM+GLP-1 and normal control(NC)groups.Rats of T2DM and T2DM+GLP-1 groups were fed with high fat diet for four weeks .The glucose infusion rate at 120 min and insulin concentration at 0,30, 60,90,120 min were measured by Hyperinsulinemic-euglycemic clamps.The gastrocnemius serine/threonine protein kinase(Akt)phosphoryl-ation was measured by Western blot .Results Compared with that of NC group ,the glucose infusion rate at 120 min of T2DM group was low-er〔(3.03±1.39)vs(6.52±1.73)mg? kg-1min-1,P<0.05〕,the skeletal muscle Akt phosphorylation levels of T2DM group was decreased. Compared with that of T2DM group,the glucose infusion rate at 120 min of T2DM+GLP-1 group was raised〔(6.09±1.75)vs(3.03± 1.39)mg? kg-1min-1,P<0.05〕,so do the Akt phosphorylation levels of skeletal muscle in T 2DM+GLP-1 group.There was no difference of insulin concentration among three groups .Conclusions GLP-1 increases glucose uptake and improves insulin sensitivity of skeletal muscle in tranquility status of T2DM rats.This action of GLP-1 is not with an increase of blood insulin concentration .