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.

参考文献

[1] Internationnal Diabetes Federation. IDF Diabetes Atlas. 7th ed[EB/OL]. Vancouver: International Diabetes Federation, 2015. http://www.diabetesatlas.org.
[2] Rubino F, Nathan DM, Eckel RH, et al. Metabolic surgery in the treatment algorithm for type 2 diabetes: a jointttatement by International Diabetes Organizations[J]. Obes Surg, 2017, 27(1): 2-21.
[3] Abbatini F, Capoccia D, Casella G, et al. Long-term remission of type 2 diabetes in morbidly obese patients after sleeve gastrectomy[J]. Surg Obes Relat Dis, 2013, 9(4): 498-502.
[4] Angrisani L, Santonicola A, Iovino P, et al. Bariatric surgery worldwide 2013[J]. Obes Surg, 2015, 25(10): 1822-1832.
[5] Tarasov AI, Griffiths EJ, Rutter GA. Regulation of ATP production by mitochondrial Ca(2+)[J]. Cell Calcium, 2012, 52(1): 28-35.
[6] Carafoli E. The fateful encounter of mitochondria with calcium: how did it happen?[J]. Biochim Biophys Acta, 2010, 1797(6-7): 595-606.
[7] Tubbs E, Theurey P, Vial G, et al. Mitochondria-associated endoplasmic reticulum membrane(MAM)integrity is required for insulin signaling and is implicated in hepatic insulin resistance[J]. Diabetes, 2014, 63(10): 3279-3294.
[8] Rowland AA, Voeltz GK. Endoplasmic reticulum-mitochondria contacts: function of the junction[J]. Nat Rev Mol Cell Biol, 2012, 13(10): 607-625.
[9] Arruda AP, Pers BM, Parlakgul G, et al. Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity[J]. Nat Med, 2014, 20(12): 1427-1435.
[10] Tubbs E. Mitochondria-associated endoplasmic reticulum membrane(MAM)integrity is required for insulin signaling and is implicated in hepatic insulin resistance[J]. Diabetes, 2014, 63(10): 3279-3294.
[11] Srinivasan K, Viswanad B, Asrat L, et al. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening[J]. Pharmacol Res, 2005, 52(4): 313-320.
[12] Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man[J]. Diabetologia, 1985, 28(7): 412-419.
[13] Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis[J]. Am J Med, 2009, 122(3): 248-256 e5.
[14] 张芳林, 李果, 刘优萍,等. 2型糖尿病大鼠模型的建立及其糖代谢特征分析[J]. 中国实验动物学报, 2002, 10(1):16-20. ZHANG Fanglin, LI Guo, LIU Youping, et al. Rat model of type 2 diabetic mellitus and its glycometabolism characters[J]. Acta Lab Anim Sci Sin, 2002, 10(1):16-20.
[15] Trung VN, Yamamoto H, Yamaguchi T, et al. Effect of sleeve gastrectomy on body weight, food intake, glucose tolerance, and metabolic hormone level in two different rat models: Goto-Kakizaki and diet-induced obese rat[J]. J Surg Res, 2013, 185(1): 159-165.
[16] 孙栋, 张光永, 刘少壮, 等. 胃袖状切除术对2型糖尿病大鼠糖脂代谢的调控作用[J]. 中华消化外科杂志, 2014, 13(7): 551-556. SUN Dong, ZHANG Guangyong, LIU Shaozhuang, et al. Regulatory effects of sleeve gastrectomy on the glucose and lipid metabolism in rats with type 2 diabetes mellitus[J]. Chin J Dig Surg, 2014, 13(7): 551-556.
[17] Defronzo RA, Simonson D, Ferrannini E. Hepatic and peripheral insulin resistance: a common feature of type 2(non-insulin-dependent)and type 1(insulin-dependent)diabetes mellitus[J]. Diabetologia, 1982, 23(4): 313-319.
[18] Lim JH, Lee HJ, Ho Jung M, et al. Coupling mitochondrial dysfunction to endoplasmic reticulum stress response: a molecular mechanism leading to hepatic insulin resistance[J]. Cell Signal, 2009, 21(1): 169-177.
[19] Rieusset J. Mitochondria and endoplasmic reticulum: mitochondria-endoplasmic reticulum interplay in type 2 diabetes pathophysiology[J]. Int J Biochem Cell Biol, 2011, 43(9): 1257-1262.
[20] Kornmann B. The molecular hug between the ER and the mitochondria[J]. Curr Opin Cell Biol, 2013, 25(4): 443-448.
[21] Szabadkai G, Bianchi K, Varnai P, et al. Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels[J]. J Cell Biol, 2006, 175(6): 901-911.
[22] Arruda AP, Hotamisligil GS. Calcium homeostasis and organelle function in the pathogenesis of obesity and diabetes[J]. Cell Metab, 2015, 22(3): 381-397.
[23] 应岚, 卢中秋, 姚咏明. 线粒体融合蛋白2的结构与功能研究进展[J]. 生理科学进展, 2016(2):108-112.
[24] de Brito OM, Scorrano L. Mitofusin 2 tethers endoplasmic reticulum to mitochondria[J]. Nature, 2008, 456(7222): 605-610.
[25] Filadi R. Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling[J]. Proc Natl Acad Sci USA, 2015, 112(17): 2174-2181.
[26] Cosson P, Marchetti A, Ravazzola M, et al. Mitofusin-2 independent juxtaposition of endoplasmic reticulum and mitochondria: an ultrastructural study[J]. PLoS One, 2012, 7(9): e46293. DOI:10.1371/journal.pone.0046293.

相关文章 15

[1]	吴逸南葛志明李方贺红姜虹张运. 自发性高血压大鼠肾脏血管紧张素转换酶2的表达[J]. 山东大学学报(医学版), 2209, 47(6): 5-.
[2]	祝林胡三元张光永丁祥就. 前列腺素E2对阻塞性黄疸大鼠小肠粘膜形态的保护作用[J]. 山东大学学报(医学版), 2209, 47(6): 12-.
[3]	孙涛张道来谢珊珊王玉卓冯玉新辛华. 酒精对原代培养的神经前体细胞间隙连接蛋白43表达的影响[J]. 山东大学学报(医学版), 2209, 47(6): 20-.
[4]	张道来孙涛谢珊珊王玉卓赵玲冯玉新辛华. 体外原代培养胎鼠大脑皮层神经元NMDAR1亚基表达的发育性变化[J]. 山东大学学报(医学版), 2209, 47(6): 28-32.
[5]	孟晓梅,郝亚平,王亮,于晓,唐与晓. 血清Isthmin1、Gremlin2水平与2型糖尿病患者视网膜病变的相关性[J]. 山东大学学报 (医学版), 2025, 63(9): 102-107.
[6]	王梦星,薛付忠,杨帆. 基于多模态交叉注意力机制融合的1型糖尿病血糖浓度预测方法[J]. 山东大学学报 (医学版), 2025, 63(8): 41-50.
[7]	申路佳,逯天威,巩伟明,赵岩松,王淑康,袁中尚. 代谢风险评分在2型糖尿病人群心血管结局预测中的应用[J]. 山东大学学报 (医学版), 2025, 63(8): 69-78.
[8]	陈莹莹,王鲁,胡锡峰,朱高培,薛付忠. 基于贝叶斯网络的2型糖尿病患者并发脑卒中风险预测[J]. 山东大学学报 (医学版), 2025, 63(8): 94-102.
[9]	陈绪军, 何国伟. 着力进一步推进动脉桥在我国冠心病冠脉旁路移植术中的应用[J]. 山东大学学报 (医学版), 2025, 63(5): 1-5.
[10]	卢圣勋,邢亚闯,罗俊辉,刘杰,何厚乐,王志强,张娜. 糖尿病患者冠脉旁路移植手术中动脉桥的研究现状[J]. 山东大学学报 (医学版), 2025, 63(5): 33-39.
[11]	杜学识,倪向敏,梁馨予,白倩,朱文艺,王建. 雌马酚对DN的保护作用及潜在靶点[J]. 山东大学学报 (医学版), 2024, 62(8): 49-58.
[12]	许沛晨,李晓博,庄向华,娄能俊,吕丽,周玲雁,牟亚朋,宋玉文,陈诗鸿. 儿童Alstrom综合征2例并文献复习[J]. 山东大学学报 (医学版), 2024, 62(3): 107-111.
[13]	赵子辉,王旭阳,张鹏,方宁宁,石端博,杨帆,杨晓玫,吴剑波. 经膈肌穿刺法快速准确评估大鼠肺动脉高压[J]. 山东大学学报 (医学版), 2024, 62(2): 20-28.
[14]	林晓倩,封茂燕,牟正. 二肽基肽酶-4抑制剂的药学特点及临床应用[J]. 山东大学学报 (医学版), 2024, 62(12): 43-48.
[15]	祁少俊,唐延金,张正铎,吴虹,张佳程,秦川,刘锐,高希宝. 补充多种微量元素对高糖饮食大鼠的保护作用[J]. 山东大学学报 (医学版), 2023, 61(7): 19-26.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed