胃旁路术对2型糖尿病大鼠肝脏葡萄糖转运体-2及葡萄糖激酶表达的影响

Expression of hepatic glucose transporter-2 and glucokinase after gastric bypass in rats with spontaneous type 2 diabetes mellitus

目的：观察胃旁路术（GBP）对自发性2型糖尿病（T2DM）大鼠（GK大鼠）肝细胞葡萄糖转运体-2（GLUT-2）及葡萄糖激酶（GCK）表达的影响，探讨其改善胰岛素抵抗的机制。方法30只8周龄雄性GK大鼠按照随机数字法分为手术组（10只）、假手术组（10只）、饮食配对组（10只），另8周龄雄性SD作为空白对照组（10只）。检测和比较术前及术后1、2、4周各组大鼠空腹血糖（FPG）、空腹胰岛素（FINS）水平，应用蛋白印迹（Western blot）及逆转录-聚合酶链反应（RT-PCR）技术检测各组术后4周肝脏组织GLUT-2、GCK mRNA及其蛋白的表达情况。结果 GK手术组术后1、2、4周FPG （（11.06±0.52） mmol／L、（7.49±0.34）mmol／L、（5.20±0.08）mmol／L）均低于术前水平（17.53±0.57）mmol／L）（均P＜0.05）；术后4周FINS由术前（11.90±0.75）mmol／L升至（14.20±1.23）mmol／L（P＜0.05）；术后4周GLUT-2、GCK mRNA及其蛋白表达明显增加（P＜0.01）。结论 GBP能上调T2DM大鼠肝细胞胰岛素信号转导通路中GLUT-2及GCK的表达，增强胰岛素受体后的信号转导，提高胰岛素的敏感性。

Objective To investigate the expression of hepatic glucose transporter-2 （ GLUT-2 ） and glucokinase（GCK）after gastric bypass（GBP）in type 2 diabetes mellitus（T2DM）GK rats and to discuss the mechanism of GBP improving insulin resistance .Methods 30 male GK rats aged 8 weeks were randomly divided into 3 groups：the operation group（10 rats）, the sham operation group（10 rats）and the diet control group（10 rats）, and 10 male SD rats aged 8 weeks were made as blank control group .The levels of fasting plasma glucose （ FPG） and fasting insulin（FINS）were measured and compared among the 4 groups before and 1,2 and 4 weeks after the operation and then the rats were sacrificed to retrieve the liver .The expressions of GLUT-2 and GCK mRNA and protein were detected by PT-PCR and Western blot respectively .Results As for GK operation group ,FPG levels at the 1st, 2nd,and 4th week after surgery （（11.06 ±0.52） mmol/L,（7.49 ±0.34） mmol/L,（5.20 ±0.08） mmol/L）respectively）were all lower than that before surgery （all P〈0.05）,and FINS level at the 4th week after surgery increased from（11.90 ±0.75）mmol/L to（14.20 ±1.23）mmol/L（P〈0.05）.The expressions of GLUT-2 and GCK mRNA and protein significantly increased in GK operation group 4 weeks after surgery （ P〈0.01 ） . Conclusion The expressions of hepatic GLUT-2 and GCK in insulin signal transmission in T2DM rats are up-regulated after GBP , which enhance the signal transmission of insulin receptor , and improves the insulin sensibility .