广西医科大学学报2019，Vol.36Issue(7)：1037-1044,8.DOI:10.16190/j.cnki.45-1211/r.2019.07.001
二甲双胍对2型糖尿病小鼠附睾脂肪组织巨噬细胞浸润及胰岛素抵抗的影响
Effect of metformin on macrophage infiltration into epididymal adipose tissue and insulin resistance in type 2 diabetic mice
摘要
Abstract
Objective:To study the effects and mechanisms of metformin on macrophage infiltration into epididymal adipose tissue and insulin resistance in type 2 diabetes (T2DM) mice.Methods:Twenty-one male C57BL/6J mice were randomly divided into 3 groups (n=7 each):control group,model group and metformin group.The rat model of T2DM was established by feeding with high-fat diet and intraperitoneal injection of streptozotoc in model group and metformin group.The control group mice were fed normal diet.Metformin (250 mg/kg) was given via gavage for 28 days.Insulin tolerance test (ITT) and oral triglyceride tolerance (OTT) test were conducted.The blood glucose level was measured.Size of epididymal fat cells and number of macrophage infiltrated epididymal adipose tissue were observed by hematoxylin-eosin (HE) staining and immunofluorescence staining,respectively.The mRNA levels of tumor necrosis factor (TNF)-α,interleukin (IL)-6,chemokine (C-C motif) ligand 2 (CCL2)and CD68 (a macrophage marker) were determined by qPCR.The protein expressions of CCL2,insulin receptor substance 1 (IRS1) and protein kinase B (AKT) were detected by western blotting.Results:Metformin reduced blood glucose and insulin levels,decreased the area under the blood glucose-time curve after insulin injection,increased glucose clearance,and alleviated insulin resistance in T2DM mice (P ＜0.01).Larger adipocytes from epididymal fat pads and large number of macrophage infiltrated obese epididymal adipose tissue were found in the model group,whereas all the changes were significantly recovered after metformin treatment.The expressions of TNF-α,IL-6,CD68 and CCL2 were down-regulated,while the phosphorylated (P)-IRS1 and P-AKT expressions were up-regulated in the metformin group compared with the model group (P ＜ 0.01).Conclusion:Metformin could reduce macrophage infiltration and alleviate insulin resistance in T2DM mice,and the mechanisms might be related to the inhibition of inflammatory response and the activation of IRS1/AKT signaling pathway.关键词
二甲双胍/CCL2/2型糖尿病/胰岛素抵抗/巨噬细胞浸润Key words
metformin/CCL2/type 2 diabetes/insulin resistance/macrophage infiltration分类
医药卫生引用本文复制引用
余培煌,唐洁芬,叶燕嫦..二甲双胍对2型糖尿病小鼠附睾脂肪组织巨噬细胞浸润及胰岛素抵抗的影响[J].广西医科大学学报,2019,36(7):1037-1044,8.基金项目
The present study was supported by the Traditional Chinese Medicine Bureau Research Project of Guangdong (No.20181024). （No.20181024）
