高脂饮食对胃旁路术后2型糖尿病大鼠糖代谢及GLP-1的影响

Effect of a high-fat diet on glucose/lipid metabolism and GLP-1 secretion in rats with type 2 diabetes after gastric bypass surgery

目的:研究高脂饮食对胃旁路术后2型糖尿病大鼠糖代谢及胰高血糖素样肽-1(glucagonlike peptide-1,GLP-1)分泌的影响,为临床研究糖尿病胃旁路术后复发提供实验数据.方法:选择♂7-8周龄SD大鼠24只,建立2型糖尿病动物模型后随机等分为对照组和高脂组,均行保留胃容积的胃旁路手术,术后对照组和高脂组分别自由进食普通词料和高脂饲料,观察10wk.术前及术后每2wk同一时间测体质量、平均进食量、空腹血糖;术前及术后第10周检测糖耐量、血清胰岛素、GLP-1,并计算胰岛素抵抗指数.结果:(1)体质量和进食量:高脂组大鼠在术后先下降后升高,10wk实验结束时对照组进食量为(40.4g±7.9g),与高脂组大鼠进食量(41.7g±6.1g)比较差异无统计学意义(P>0.05);10wk实验结束时两组大鼠的体质量均较术前体质量有明显增加(P<0.05),且高脂组大鼠的体质量334.2g±47.5g明显高于对照组(302.4g±34.1g)(P<0.05);(2)空腹血糖、糖耐量、胰岛素、胰岛素抵抗指数:大鼠术后空腹血糖均逐渐降低,但随时间延长高脂组大鼠空腹血糖开始出现升高,第8周开始高脂组空腹血糖高于对照组(P>0.05);在第10周实验结束时,对照组及高脂组喂养的2型糖尿病大鼠糖耐量均较术前下降(分别较实验前AUC减小11.5%和5.2%);在术后第4周时对照组和高脂组空腹胰岛素水平及胰岛素抵抗指数均较术前有所升高(P<0.05),第10周时对照组空腹胰岛素水平和胰岛素抵抗指数无明显变化,而高脂组空腹胰岛素水平下降、胰岛素抵抗指数升高,但与术前差异仍有统计学意义(P<0.05);(3)GLP-1:术后10wk时对照组和高脂组大鼠的血清GLP-1浓度分别为22.69pmol/L±3.87pmol/L、39.33pmol/L±2.77pmol/L,均较术前8.15pmol/L±1.40pmol/L、7.76pmol/L±0.84pmol/L升高(P<0.05),其中高脂组GLP-1浓度增加的更为显著.结论:胃旁路手术可以降低2型糖尿病大鼠的血糖并改善胰岛素抵抗,在高脂饮食刺激下术后未见严重糖代谢紊乱,其机制可能与GLP-1分泌增加有关.

AIM： To assess the effect of a high-fat diet on glucose/lipid metabolism and glucagon-like peptide-1 （GLP-1） secretion in rats with type 2 diabetes after gastric bypass surgery. METHODS： Twenty-four SD rats were used to induce type 2 diabetes and then randomly divided into either a control group （n = 10） or a high-fat diet group （n = 10）. After gastric bypass surgery, the control group and high-fat diet group were fed a normal diet and a high-fat diet for 8 wk, respectively. Food intake, body weight, ,fasting plasma glucose and the levels of GLP-1 were measured. RESULTS： The body weight and average food intake first decreased and then gradually increased in both groups. At week 10 after surgery, there was a significant difference in body weight between the control group and high fat diet group （302.4 g ± 34.1 g vs 334.2 g ± 47.5 g, P 0.05）. Fasting plasma glucose gradually decreased after surgery in both groups; however, fasting plasma glucose began to increase with the prolongation of time in the high-fat diet group. At week 8, fasting plasma glucose was higher in the high-fat diet group than in the control group. At week 4 after surgery, insulin level increased and insulin resistance index decreased in both groups. The level of GLP-1 at week 10 after surgery significantly increased in the high-fat diet group compared to the control group （39.33 pmol/L ± 2.77 pmol/L vs 22.69 pmol/L ± 3.87 pmol/L, P 0.05）. CONCLUSION： Gastric bypass reduces blood glucose in rats with type 2 diabetes. A serious disturbance of carbohydrate metabolism stimulated by a high fat diet was not observed in rats after gastric bypass, and the underlying mechanism may be related to increased secretion of GLP-1.