中国组织工程研究 第21卷 第12期 2017–04–28出版
Chinese Journal of Tissue Engineering Research April 28, 2017 Vol.21, No.12
ISSN 2095-4344 CN 21-1581/R CODEN: ZLKHAH 1909
www. CRTER .org ·研究原著·
秦凤,女,1981年生,四川省遂宁市人,汉族,主治医师,主要从事内分泌疾病和代谢病的研究。
通讯作者:张惠莉,教授,主任医师,青海大学附属医院内分泌科,青海省西宁市 810001
中图分类号:R318 文献标识码:B 文章编号:2095-4344 (201712-01909-06 稿件接受:2017-02-22
Qin Feng, Attending physician, Department of Endocrinology, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China
Corresponding author: Zhang Hui-li, Professor, Chief physician, Department of Endocrinology, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China
二甲双胍对2型糖尿病模型大鼠胰岛素抵抗的影响
秦 凤1,李春亮2,张惠莉1 (1青海大学附属医院内分泌科,青海省西宁市 810001;2青海大学医学院,青海省西宁市 810016 引用本文:秦凤,李春亮,张惠莉. 二甲双胍对2型糖尿病模型大鼠胰岛素抵抗的影响[J].中国组织工程研究,2017,21(12:1909-1914.
DOI:10.3969/j.issn.2095-4344.2017.12.018 ORCID: 0000-0003-2043-9136(秦凤 文章快速阅读: 文题释义:
胰岛素抵抗:是指各种原因使胰岛素促进葡萄糖摄取和利用的效率下降,机体代偿性的分泌过多胰岛素产生高胰岛素血症,以维持血糖的稳定。胰岛素抵抗易导致代谢综合征和2型糖尿病。 胰岛素受体:是一个四聚体,由两个α亚基和两个β亚基通过二硫键连接。两个α亚基位于细胞质膜的外侧,其上有胰岛素的结合位点;两个β亚基是跨膜蛋白,起信号转导作用。
摘要
背景:目前已经发现的脂肪代谢相关基因有10余种,脂肪代谢相关基因介导的内分泌功能失常是导致胰岛素抵抗发生、发展的重要病理基础。 目的:分析二甲双胍对2型糖尿病大鼠血脂水平、胰岛素抵抗相关基因及肝脏和胰腺组织病理学变化的影响。 方法:通过4周高脂饮食结合腹腔注射链脲佐菌素(35 mg/kg建立2型糖尿病大鼠模型。4周高脂饮食时,模型大鼠同时口服二甲双胍4周[400
mg/(kg?d],对照组大鼠正常饮食,腹腔未注射链脲佐菌素。然后利用半定量RT-PCR 、组织病理学及生化检测等方法进行相关分析。
结果与结论:①二甲双胍通过恢复2型糖尿病大鼠正常血脂,改善胰岛素抵抗症状;②二甲双胍上调脂肪代谢相关胰岛素受体和基因乙酰辅酶A 氧化酶, 肉毒碱棕榈酰转移1和过氧化物酶体增殖物激活受体α;③二甲双胍治疗下调胎球蛋白A 和视黄醇结合蛋白,2型糖尿病大鼠中降低的脂滴包被蛋白也恢复正常;④在胰腺内,二甲双胍处理诱导胰岛素分泌和胰腺β细胞再生;⑤结果说明,二甲双胍通过调节胎球蛋白A 、视黄醇结合蛋白4、脂滴包被蛋白和脂肪代谢相关基因,改善2型糖尿病引起的胰岛素抵抗。 关键词:
组织构建;组织工程;二甲双胍;2型糖尿病;胰岛素抵抗;机制 主题词: 糖尿病, 2型;二甲双胍;胰岛素;组织工程
Effect of metformin on the insulin resistance in a rat model of type 2 diabetes mellitus
Qin Feng1, Li Chun-liang2, Zhang Hui-li1 (1Department of Endocrinology, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China; 2Medical College of Qinghai University, Xining 810016, Qinghai Province, China
Abstract
BACKGROUND: More than 10 kinds of lipid metabolism-related genes have been found, and endocrine
dysfunction mediated by these genes is an important pathological basis for the occurrence and development of insulin resistance.
OBJECTIVE: To investigate the effects of metformin on serum lipid profiles and the expression levels of various
秦凤,等. 二甲双胍对2型糖尿病模型大鼠胰岛素抵抗的影响 P .O. Box 10002, Shenyang 110180 www.CRTER.org
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genes associated with insulin resistance, as well as the histopathological changes of the liver and pancreas in rats with type 2 diabetes melitus.
METHODS: A type 2 diabetes mellitus rat model was established by feeding a high-fat diet to the rats for 4 weeks, combined with the intraperitoneal injection of streptozotocin (35 mg/kg. In the meanwhile, metformin was administered orally (400 mg/kg?d (model group or nothing (control group. Semi-quantitative RT-PCR, histopathological and biochemical examinations were then performed.
RESULTS AND CONCLUSION: Metformin improved the symptoms of insulin resistance by normalizing the serum lipid profiles in the diabetic rats. Furthermore, metformin upregulated the expression levels of insulin receptors and genes associated with lipid metabolism, including acyl-CoA oxidase, carnitine palmitoyl transferase-1 and peroxisome proliferator activated receptor-α. In addition, metformin downregulated the expression levels of fetuin-A and retinol binding protein-4, and improved the expression of perilipin that had been reduced in the type 2 diabetes mellitus rats. Metformin was shown to induce positive signaling for insulin and the regeneration of pancreatic β cells in the pancreas. These results suggest that metformin ameliorates the insulin resistance induced by type 2 diabetes mellitus via
regulating the expression levels of fetuin-A, retinol binding protein-4, perilipin and various genes associated with lipid metabolism.
Subject headings: Diabetes Mellitus, Type 2; Metformin; Insulin; Tissue Engineering
Cite this article: Qin F, Li CL, Zhang HL. Effect of metformin on the insulin resistance in a rat model of type 2 diabetes mellitus. Zhongguo Zuzhi Gongcheng Yanjiu. 2017;21(12:1909-1914.
0 引言 Introduction
2型糖尿病是最常见的糖尿病,在世界范围内占糖尿病总数的90%[1]。2型糖尿病发病是由于胰岛β细胞破坏导致胰岛素分泌不足以及胰岛素抵抗(insulin resistance,IR [2]。胰岛素抵抗对各种器官和组织产生影响,对中枢神经系统的影响是可能导致肥胖,因为中枢神经系统胰岛素活性增加会提高食欲[3];在脂肪组织中,胰岛素抵抗会引起高脂血症,脂肪组织可分泌细胞因子和激素,而脂肪膨胀破坏其内分泌功能,从而促进胰岛素抵抗[4];在胰腺组织,胰岛素抵抗损坏胰岛β细胞再生[5]。Sam 等[6]发现由肝脏分泌的胎球蛋白A ,与肥胖、胰岛素抵抗和非酒精性脂肪肝有关。胎球蛋白A 通过抑制肝和骨骼肌中胰岛素受体酪氨酸激酶影响胰岛素信号转导,除了使胰岛素受体自身磷酸化,也可导致胰岛素抵抗[7]。另外一个胰岛素抵抗可靠指标是视黄醇结合蛋白,其在胰岛素抵抗和2型糖尿病患者动脉粥样硬化中发挥关键作用。脂滴包被蛋白作为一种重要的脂肪代谢相关蛋白包被于脂滴的表面,对脂滴代谢具有重要的调控作用。先前的研究表明脂滴包被蛋白活性与胞浆内脂滴的生理功能及与肥胖相关的疾病如胰岛素抵抗相关[8]。
二甲双胍是糖尿病的最常用的药物之一。二甲双胍改善胰岛素敏感性,减少糖异生,促进葡萄糖吸收,降低肝糖原产生。二甲双胍对一些胰岛素抵抗和高胰岛素血症影响的组织,如骨骼肌,脂肪组织和血管内皮细胞,具有多重效应[9]。虽然二甲双胍在临床中已应用了40多年,但其确切作用机制尚未完全阐明。因而,实验目的是评价二甲双胍对2型糖尿病大鼠胰岛素抵抗影响及相关机制探讨。
二甲双胍对2型糖尿病模型大鼠胰岛素抵抗的影响(精)
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