Roux-en-Y胃旁路术对肥胖大鼠肾脏糖异生的影响

摘要

Objective To investigate the effect of Roux-en-Y gastric bypass surgery on renal gluconeogenesis, and to explore the mechanism of improving glucose control and insulin sensitivity in obese rats.Methods Rats were randomly divided into the obese group (n=30) consumed high-fat diet (HFD) and control group (NC group, n=8).Top 24 of animals fed HFD by change in body mass were subdivided into three groups: obese control group (OB group, n=8), obese under RYGB group (RYGB group, n=8) or sham-operation (sham group, n=8).Intraperitoneal glucose tolerance tests (IPGTT) were performed meanwhile the AUC of blood glucose concentration-time after surgery.Fasting glucose, insulin and lipid were measured respectively and HOMA-IR were calculated.The mRNA level and protein level of the key enzymes (G6P and PEPCK) of renal gluconeogenesis were examined with RT-PCR and Western blot respectively.Results Compared with OB group and Sham group, the body mass, lipid, blood glucose, insulin, HOMA-IR and AUG were significantly decreased (P<0.05), the expression of G6P and PEPCK mRNA and protein were significantly reduced(P<0.05) in RYGBgroup.Conclusions Roux-en-Y gastric bypass surgery can improve glucose control and insulin resistance, which may be related to the decreased level of mRNA, protein of G6P and PEPCK, reduced gluconeogenesis and glucose output in renal cortex.%目的研究胃旁路术后肥胖大鼠糖代谢及肾脏糖异生的改变.方法将大鼠分为:对照组、肥胖模型组(高脂饮食诱导)、假手术组和手术组(胃旁路术干预模型组).术后检测血脂、血糖和胰岛素并计算胰岛素抵抗指数(HOMA-IR),行葡萄糖耐量实验并计算曲线下面积(AUG);q-PCR检测肾脏葡萄糖6磷酸酶(G6P)和磷酸烯醇式丙酮酸羧激酶(PEPCK)mRNA表达,Western blot检测G6P、PEPCK、p-IRS1和p-Akt蛋白表达.结果相较肥胖模型组和假手术组,手术组大鼠体质量、血糖、血脂、胰岛素、HOMA-IR和AUG均明显降低(P<0.05);G6P和PEPCK mRNA表达及蛋白含量明显降低(P<0.05);p-IRS1和p-Akt蛋白含量明显升高(P<0.05).结论胃旁路术能够显著改善肥胖大鼠糖代谢和胰岛素抵抗,其机制可能与肾脏糖异生关键酶表达降低,肾脏糖异生及糖输出减弱有关.