摘要
目的建立十二指肠-空肠转流手术(duodenal-jejunal bypass surgery,DJB)动物模型,观察术后GK大鼠胰岛素抵抗情况的变化,研究DJB手术治疗2型糖尿病的机理。方法雄性Wistar大鼠为空白对照组;雄性GK大鼠分为模型对照组和DJB手术组。分别于手术后3、6和9周每组随机抽取6只动物进行高胰岛素-正葡萄糖钳夹实验;钳夹实验结束后1周,检测肝脏Gc K、G6P以及PEPCK mRNA表达情况以及骨骼肌细胞膜GLUT4含量变化。结果术后3周和6周,DJB手术组动物的葡萄糖输注率(GIR)较模型对照组差异无显著性(P>0.05),肝脏Gc K、G6P以及PEPCK mRNA表达量较模型对照组差异无显著性(P>0.05);术后9周,DJB手术组动物的葡萄糖输注率(GIR)显著高于模型对照组(P<0.05),肝脏Gc K表达量DJB手术组显著高于模型对照组(P<0.05),而G6P以及PEPCK mRNA表达量显著低于模型对照组(P<0.05);DJB手术后3、6和9周,DJB手术组骨骼肌细胞膜GLUT4的含量较模型对照组差异无显著性(P>0.05)。结论 DJB手术改善血糖的水平是通过改善体内肝脏组织的胰岛素抵抗,通过调节糖代谢酶的表达,进而提高肝脏葡萄糖摄取并抑制肝脏糖异生作用。在实验周期内,DJB手术对于骨骼肌组织的胰岛素抵抗未发现有明显改善,提示DJB手术治疗2型糖尿病的效果与时间有一定关系。
Objective To establish a Goto-Kakizaki （ GK） rat model of duodenal-jejunal bypass（ DJB） and ob-serve the changes in insulin-resistance after surgery, and to explore the mechanism of DJB surgery in treatment of type 2 di-abetes mellitus.Methods Male Goto-kakizaki diabetic rats（GK,n=36）were used as experiment group and 18 healthy male Wistar rats as blank group.GK rats were randomly divided into two groups： diabetic control group and DJB surgery group （ n=18） .Euglycemic-hyperinsulinemic clamp technique was performed in 6 rats randomly taken from each group at third week, sixth week and ninth week after surgery, respectively.The expression levels of Gck, G6P, PEPCK mRNA in the liver and GLUT4 content on skeletal muscle cell plasma membrance were detected one week after the clamp test. Results In the DJB surgery group at the end of third week and sixth week after surgery, the levels of glucose infusion rates and the expression levels of Gck, G6P, PEPCK mRNA in the liver showed no statistically significant difference as com-pared with the diabetic control group （P〉0.05）.In the DJB surgery group at the end of 9th week after surgery, the glu-cose infusion rate and expression level of Gck mRNA in the liver were significantly higher, and the expression of G6P and PEPCK mRNA was significantly lower than those in the diabetic control group （ P〈0.05 for all） .At the three time points （3rd week, 6th week and 9th week after surgery）, there was no significant difference in the GLUT4 content on skeletal muscle cell plasma membrane between the diabetic control group and DJB surgery group （ P〉0.05 for all） .Conclusions Our results indicate that the mechanism of DJB surgery improving blood glucose level may be closely related to the amel-ioration of insulin-resistance in the liver, thereby augmenting glucose uptake and inhibiting gluconeogenesis in liver through the regulation of glucose metabolism-related enzymes.There is no significant improvement in insulin-resistance in the skele-tal muscles during the experiment period.This result implies that the effect of DJB surgery on type 2 diabetes is related to the duration of therapy.
出处
《中国实验动物学报》
CAS
CSCD
北大核心
2015年第2期159-164,共6页
Acta Laboratorium Animalis Scientia Sinica
基金
上海市科学技术委员会科研计划项目(No.11140900702)
关键词
2型糖尿病
GK大鼠
十二指肠-空肠转流术
高胰岛素-正葡萄糖钳夹实验
Type 2 diabetes mellitus
Goto-Kakizaki rats
Duodenal-jejunal bypass surgery
Euglycemic-hyperin-sulinemic clamp technique
Insulin resistance
