肝线粒体相关内质网膜在袖状胃切除术改善糖尿病大鼠胰岛素敏感性中的作用

doi:10.6040/j.issn.1671-7554.0.2017.205

摘要/Abstract

摘要： 目的探讨袖状胃切除术(SG)对糖尿病大鼠肝脏线粒体相关内质网膜(MAMs)的影响及其机制。方法建立Wistar大鼠糖尿病模型,选取20只随机分为SG手术组(n=10)和SHAM假手术组(n=10),测量两组大鼠术前术后的体质量、进食量以及胰岛素敏感性变化,并在术后12周取大鼠肝脏检测MAMs中1,4,5-三磷酸肌醇受体(IP3R)、线粒体融合蛋白2(Mfn2)、葡萄糖调节蛋白75(Grp75)、线粒体钙单向转运体(MCU)等蛋白分子的表达量变化。结果与SHAM组比较,SG组术后4周起进食量减少,6周起体质量降低;术后第2、12周,口服葡萄糖耐量试验曲线下面积、胰岛素耐量试验曲线下面积、稳态模型评估胰岛素抵抗明显减少;SG组术后MAMs中与钙离子平衡相关的IP3R、MCU及与内质网线粒体连接相关的Mfn2等蛋白表达量均低于SHAM组(P<0.05)。结论糖尿病大鼠SG术后胰岛素的敏感性改善可能与术后MAMs钙离子通道相关蛋白的表达下降有关。

关键词: 袖状胃切除术, 大鼠, 线粒体相关内质网膜, 糖尿病

Abstract: Objective To investigate the effects of sleeve gastrectomy(SG)on mitochondria-associated membranes in diabetic rats and the mechanism. Methods Models of Wistar rats with type 2 diabetes mellitus were established. A total of 20 models were randomly divided into surgery group(SG, n=10)and sham operation group(SHAM, n=10). The changes of body weight, food intake and insulin sensitivity were measured before and after operation. At the end of week 12 after surgery, liver samples were collected to detect protein expressions of inositol 1,4,5-trisphosphate receptor(IP3R), mitochondrial fusion protein 2(Mfn2), glucose-regulated protein 75(Grp75), and mitochondrial calcium uniporter(MCU)in mitochondria-associated membranes. Results Compared with SHAM group, SG group showed significant food intake reduction from week 4, and weight loss from week 6 postoperatively. In week 2 and 12, the areas under the curve of the oral glucose tolerance test, insulin tolerance test, and homeostasis model assessment of insulin resistance(HOMA-IR)were significantly decreased in SG group. The SG group had lower expressions of IP3R and MCU, which were associated with calcium homeostasis, and Mfn2, which was correlated with connection between mitochondria and endoplasmic reticulum(P<0.05). Conclusion The improvement of insulin sensitivity after SG in diabetic rats may be related to the decreased expression of MAMs proteins associated with calcium channel.

Key words: Sleeve gastrectomy, Rats, Mitochondria-associated membranes, Diabetes

中图分类号:

R656.6+1

谢海滨,武群政,刘少壮,黄鑫,程玉刚,胡三元,张光永. 肝线粒体相关内质网膜在袖状胃切除术改善糖尿病大鼠胰岛素敏感性中的作用[J]. 山东大学学报（医学版）, 2017, 55(10): 36-40.

XIE Haibin, WU Qunzheng, LIU Shaozhuang, HUANG Xin, CHENG Yugang, HU Sanyuan, ZHANG Guangyong. Role of mitochondria-associated membranes in the improvement of insulin sensitivity in diabetic rats after sleeve gastrectomy[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(10): 36-40.

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