EGCG对2型糖尿病大鼠胰岛素抵抗影响及机制

刘畅; 梁惠; 刘爽; 陈思淼; 张婉君; 马爱国; 张华琦

doi:10.11847/zgggws1124868

EGCG对2型糖尿病大鼠胰岛素抵抗影响及机制

Effect and mechanism of epigallocatechin-3-gallate on insulin resistance in type 2 diabetic rats

摘要

摘要:
目的观察表没食子儿茶素没食子酸酯（EGCG）对2型糖尿病大鼠胰岛素抵抗的影响并探讨其机制。
方法大鼠随机分为对照组（10只）和造模组（80只），造型组大鼠采用高脂高糖饲料喂养结合腹腔一次性注射35 mg/kg链脲佐菌素（STZ）构建2型糖尿病模型，将建模成功的50只大鼠随机分为模型组（蒸馏水）、二甲双胍组（300 mg/kg）、EGCG低、中、高剂量组（25、50、100 mg/kg），每组10只；灌胃干预6周后，测定大鼠体重和空腹血糖（FBG）与血清胰岛素（INS）水平，计算胰岛素敏感性指数（ISI）和胰岛素抵抗指数（HOMA-IR）。利用实时荧光定量PCR（real time-PCR）和蛋白质印迹法（WB）检测大鼠肝脏磷酸烯醇式丙酮酸羧激酶（PEPCK）和骨骼肌葡萄糖转运体4（GLUT4）mRNA和蛋白表达水平。
结果与对照组比较，模型组大鼠体重明显降低、空腹血糖、HOMA-IR明显升高（P < 0.05）；与模型组比较，EGCG中剂量组大鼠血清INS、ISI、HOMA-IR均明显下降（P < 0.05）。与对照组比较，模型组大鼠肝脏PEPCK mRNA与蛋白表达水平升高、骨骼肌GLUT4 mRNA与蛋白表达水平降低（P < 0.05）；与模型组比较，EGCG高剂量组大鼠肝脏PEPCK的mRNA和蛋白表达水平明显降低、骨骼肌GLUT4 mRNA和蛋白表达水平明显升高（P < 0.05）。
结论 EGCG可在一定程度上改善2型糖尿病大鼠的胰岛素抵抗，其机制可能与增强胰岛素敏感性和抑制肝脏糖异生功能并增加骨骼肌中葡萄糖的转运有关。

Abstract:
Objective To observe the effect and mechanism of epigallocatechin-3-gallate (EGCG) on insulin resistance in type 2 diabetic rats.
Methods Totally 90 Sprague-Dawley rats were randomly divided into a normal control group (10 rats) and a model group (80 rats). The rat model of type 2 diabetes mellitus (T2DM) was established with high fat and sugar diet combined with intraperitoneal injection of 35 mg/kg streptozotocin (STZ). Fifty T2DM model rats were randomly divided into five groups (10 in each group): a positive control group (with distilled water), metformin group (300 mg/kg), low-, moderate-, and high-EGCG group (25, 50, 100 mg/kg). By the end of 6-week intragastric treatment, the body weight, fasting blood glucose (FBG) and serum insulin (INS) level were measured, and insulin sensitivity index (ISI) and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. The mRNA and protein expression of phosphoenolpyruvate carboxykinase (PEPCK) in liver tissue and glucose transporter 4 (GLUT4) in skeletal muscle were detected with real-time fluorescence quantitative PCR (real time-PCR) and Western blot.
Results Significantly decreased body weight but increased FBG and HOMA-IR were detected in T2DM model rats compared to those in the normal control rats (P < 0.05 for all). Significantly lower serum INS but higher ISI and HOMA-IR were observed in the rats of moderate-EGCG group than those in the T2DM model rats (all P < 0.05). In comparison to the normal control rats, the T2DM model rats had significantly increased PEPCK mRNA expression in liver tissues but decreased GLUT4 mRNA expression in skeletal muscles (both P < 0.05); while, the rats treated with high-EGCG had significantly lower PEPCK mRNA expression in liver tissues but higher GLUT4 mRNA expression in skeletal muscles than the T2DM model rats (both P < 0.05).
Conclusion EGCG can improve insulin resistance to a certain extent in type 2 diabetic rats and the effect may be related to the enhancement of insulin sensitivity, the inhibition of hepatic gluconeogenesis, and the increase of glucose transport in skeletal muscle.

HTML全文

参考文献(27)

施引文献

资源附件(0)