瘦素改善2型糖尿病ob/ob小鼠糖和脂质代谢作用机制的探讨

杨成伟; 王取南; 陈可洋

doi:10.16462/j.cnki.zhjbkz.2016.09.020

瘦素改善2型糖尿病ob/ob小鼠糖和脂质代谢作用机制的探讨

doi: 10.16462/j.cnki.zhjbkz.2016.09.020

杨成伟¹,
王取南^1, ,,
陈可洋^2, ,

1. 安徽医科大学公共卫生学院卫生毒理学系, 安徽合肥 230032;
2. 安徽医科大学公共卫生学院卫生检验系, 安徽合肥 230032

基金项目:

安徽省自然科学基金（1508085MH162）；安徽医科大学留学回国科研启动基金（2013年）

详细信息

作者简介:
杨成伟(1991-),男,安徽六安人,在读硕士研究生。主要研究方向:糖尿病糖脂代谢。

中图分类号: R587.1;R181.2
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- 被引次数: 0
出版历程
- 收稿日期: 2016-03-03
- 修回日期: 2016-05-27

A study on possible mechanism of leptin in improving glucose and lipids metabolism in type 2 diabetic ob/ob mice

1. Department of Toxicology, School of Public Health, Anhui Medical University, Hefei 230032, China;
2. Department of Sanitary Inspection, School of Public Health, Anhui Medical University, Hefei 230032, China

摘要

摘要: 目的研究瘦素对2型糖尿病小鼠糖脂代谢及肝功能的改善作用，并从氧化应激、内质网应激和胰岛素抵抗等方面探讨其可能机制。方法选用瘦素缺陷的ob/ob小鼠作为2型糖尿病模型，根据是否给予瘦素处理分为两组（1 mg/（kg·d）, 腹腔内注射）；选用野生型C57BL/6J小鼠为正常对照。测定血清甘油三酯（triglyceride，TG）和总胆固醇（total cholesterol，TC）反映脂质代谢状况，血清谷丙转氨酶（alanine transaminase，ALT）和谷草转氨酶（aspartate aminotransferase，AST）反映肝功能；酶联免疫吸附实验测定胰岛素水平；Western blot检测氧化应激指标还原烟酰胺腺嘌呤二核苷酸磷酸氧化酶 4（nicotinamide adenine dinucleotide phosphate reduced oxidase 4，NOX4）和过氧化氢酶（catalase，CAT）、内质网应激标志葡萄糖调节蛋白78（glucose-regulated protein 78，GRP78）水平，胰岛素调控糖脂代谢通路蛋白激酶B（protein kinase B，AKT）的激活。结果与野生型小鼠比较，ob/ob小鼠血糖、TG和TC、ALT和AST活力以及胰岛素水平皆升高（均有P<0.05）；与ob/ob小鼠比较，经瘦素处理的ob/ob小鼠血糖、TG和TC、ALT和AST活力以及胰岛素水平皆下降（均有P<0.05）。与野生型小鼠比较，ob/ob小鼠肝脏NOX4和GRP78水平增高（均有P<0.05），CAT和p-AKT水平降低（均有P<0.05）；与未经瘦素处理的ob/ob小鼠相比，经瘦素处理的ob/ob小鼠肝脏中NOX4、GRP78降低（均有P<0.05），CAT和p-AKT升高（均有P<0.05）。结论瘦素可改善2型糖尿病小鼠糖脂代谢和肝功能，作用机制可能与其减轻肝脏氧化应激和内质网应激以及恢复对胰岛素的敏感性有关。
- 瘦素 /
- 糖尿病,2型 /
- 胰岛素
Abstract: Objective To investigate the improvement of leptin on liver function, glucose and lipids metabolism and explore possible mechanism from oxidative stress, endoplasmic reticulum stress and insulin resistance. Methods Choosing leptin-deficient ob/ob mice as animal model of type 2 diabetes mellitus and dealt with or without leptin respectively (1 mg/(kg·d), intraperitoneal injection), C57BL/6J wild-type mice were chonse as control group. Roche ACCU-CHEK was used to measure serum triglyceride (TG) and total cholesterol (TC) which reflected lipids metabolism, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) which reflected liver function, the serum level test of insulin with enzyme linked immunosorbent assay, detecting the protein expression level with western blot including oxidative stress indicator-NOX4, anti-oxidative enzyme indicator-CAT, endoplasmic reticulum stress symbol indicator-GRP78, AKT activation in the classical pathway of glucose and lipids metabolism regulated by insulin. Results Compared with wild-type mice, the blood glucose, serum TG and TC, serum ALT and AST activity, and serum insulin level of ob/ob mice increased significantly (all P<0.05); compared with ob/ob mice without leptin, the blood glucose, serum TG and TC, serum ALT and AST activity, and serum insulin level of ob/ob mice dealt with leptin decreased significantly (all P<0.05). Compared with wild-type mice, there were significant increas in NOX4 and GRP78 expression level (all P<0.05), CAT and p-AKT expression level in ob/ob mice decreased significantly (all P<0.05). There were significant decrease in NOX4 and GRP78 expression level compared with ob/ob mice (all P<0.05), CAT and p-AKT expression level of ob/ob mice dealed with leptin increased significantly (all P<0.05). Conclusions Leptin could improve the glucose and lipids metabolism and liver function of type 2 diabetic mice significantly, which might related to the mechanism of leptin reducing liver oxidative stress and endoplasmic reticulum stress, and restoring the sensitivity to insulin.
- Leptin /
- Diabetes mellitus, type 2 /
- Insulin

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参考文献(18)

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