Effect of metformin on the insulin resistance in a rat model of type 2 diabetes mellitus

doi:10.3969/j.issn.2095-4344.2017.12.018

Abstract

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
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.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Diabetes Mellitus, Type 2, Metformin, Insulin, Tissue Engineering

CLC Number:

R318

Qin Feng1, Li Chun-liang2, Zhang Hui-li1. Effect of metformin on the insulin resistance in a rat model of type 2 diabetes mellitus[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(12): 1909-1914.

Figures/Tables 3

2.3 二甲双胍对糖尿病诱导脂肪代谢相关基因的影响半定量RT-PCR分析各组乙酰辅酶A氧化酶、肉毒碱棕榈酰转移1和胎球蛋白A。在胰岛素抵抗组，脂质代谢紊乱并且与脂质代谢相关的基因表达改变，半定量RT-PCR显示大鼠肝脏乙酰辅酶A氧化酶、肉毒碱棕榈酰转移1和胎球蛋白A表达改变，乙酰辅酶A氧化酶和肉毒碱棕榈酰转移1表达水平降低提示胰岛素抵抗组中脂肪酸氧化减少(图1A、B)。而二甲双胍组乙酰辅酶A氧化酶和肉毒碱棕榈酰转移1表达水平增高(图1A、B)，提示二甲双胍改善2型糖尿病大鼠血脂异常。与乙酰辅酶A氧化酶和肉毒碱棕榈酰转移1比较，胰岛素抵抗组胎球蛋白A表达增高，二甲双胍组胎球蛋白A表达降低，接近正常水平(图1C)。 2.4 二甲双胍对糖尿病诱导胰岛素信号分子的影响半定量RT-PCR分析各组肝胰岛素受体底物(IRS-1和IRS-2)、脂肪酸合成酶和过氧化物酶体增殖物激活受体α。如图2A，B所示，胰岛素抵抗组中胰岛素信号分子IRS-1和IRS-2表达降低。相比较，胰岛素抵抗组中脂肪酸合成酶表达增高，而二甲双胍组脂肪酸合成酶表达降低，接近正常(图2C)。二甲双胍组过氧化物酶体增殖物激活受体α表达增高(图2D)。 2.5 二甲双胍对脂肪组织脂滴包被蛋白和视黄醇结合蛋白4表达的影响半定量RT-PCR分析各组脂肪组织脂滴包被蛋白和视黄醇结合蛋白4表达。如图3所示，胰岛素抵抗组中脂滴包被蛋白表达显著降低，而视黄醇结合蛋白4表达水平增加。二甲双胍组脂滴包被蛋白表达恢复正常，而视黄醇结合蛋白4表达降低。 2.6 肝组织病理学和胰腺免疫组织化学改变对照组大鼠肝组织表现出正常的肝细胞结构，肝细胞以中央静脉为中心呈放射状排列，网眼间有窦状隙和血窦(图4A)。胰岛素抵抗组由于脂肪或小脂滴在肝细胞浆中积累，导致肝细胞形态改变(图4B)。而二甲双胍组肝细胞形态恢复正常(图4C)。对照组大鼠胰腺结构正常，胰腺β细胞正常分泌胰岛素(图4D)。然而，胰岛素抵抗组大鼠胰腺组织胰岛素表达减少，胰腺β细胞轻度萎缩(图4E)。最后，二甲双胍组胰岛素表达正常，胰腺β细胞再生(图4F)。"

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