胃转流术对2型糖尿病大鼠脂肪组织胰岛素抵抗的影响

Influence on adipose tissue insulin resitance of type 2 diabetic rats after gastric bypass operation

目的 观察胃转流术（GBP）对2型糖尿病（T2DM）大鼠脂肪组织胰岛素受体底物1（IRS-1）、磷酸肌醇3激酶（PI3K）蛋白表达的影响,探讨GBP改善胰岛素抵抗的机制.方法 将36只T2DM SD大鼠随机分为手术组（T组）、饮食控制组（F组）和糖尿病对照组（C组）,每组12只.术前及术后第1、2、4、8周测空腹血糖（FPG）、空腹胰岛素（FINS）并计算术前及术后第8周胰岛素敏感指数（QUICKI）,Western blot检测各组术后第8周脂肪组织IRS-1、PI3K蛋白的表达.结果 与术前和同时间点对照组比较,GBP手术组大鼠FPG术后第1周开始降低,至术后第8周时T组大鼠FPG由术前的（17.28 ±2.15） mmol/L降至（5.79±1.83） mmol/L（P ＜0.05）；T组大鼠FINS经历了先升后降的过程,至第8周时FINS降至（7.69±1.73） mU/L（P＜0.05）；QUICKI在术后第8周时高于术前及对照组（P＜0.05）；手术组IRS-1、PI3K表达水平均显著高于对照组（P＜0.05）.结论 GBP可改善脂肪细胞IRS-1/PI3K胰岛素信号转导通路,纠正脂肪细胞的胰岛素抵抗,提高T2DM大鼠的胰岛素敏感性.

Objective To investigate the expressions of insulin receptor substrate-1 （IRS-1） and phosphatidylinositol 3 kinase （PI3K） in adipose tissue of type 2 diabetic rats after gastric bypass operation,and to study the possible mechanism of adipose tissue insulin resitance.Methods Thirty-six type 2 diabetic SD rats were randomly divided into 3 experimental groups：Gastric bypass operation group （T group）,food control group （F group）,type 2 diabetes rats control group （C group）,12 rats in each group.Plasma glucose concentration,insulin,were measured in preoperative and postoperative at week 1,2,4 and 8.Quantitative insulin sensitivity check index （QUICKI） were measured in preoperative and postoperative at week 8.And the protein of adipose tissue IRS-1and PI3K were measured at week 8 after operative.Results The fasting blood glucose of T group rats at the first week were so obviously lower than F and C group that at every point in time after surgery（P 〈 0.05）.FINS of T group have a progress of fist increase at the first week and then decrease in postoperative 8 weeks,FINS was （7.69 ± 1.73） mU/L（P〈0.05）,while F and C group had no significant changes post operation.The change of QUICKI：T group had increased dramaticly,from preoperative 0.43 ±0.05 to 0.61 ±0.05 （P 〈0.05） in 8 weeks post operation,while F and C group had no significant changes post operation.The result of Western blotting：compared T group to C group,a significantly increase in the expression of IRS-1 and PI3K protein respectively after eight weeks postoperative（P 〈 0.05）.However,the corresponding indicators of F and C group have no significantly difference.Conclusion GBP can improve the expression of IRS-1/PI3K insulin signal transmission in adipose tissue,thus increase the insulin sensitivity and improve insulin resistance of adipose tissue.