[酒精对大鼠骨骼肌胰岛素敏感性及胰岛素受体底物-1 mRNA表达的影响]

[Influence of alcohol on insulin sensitivity and insulin receptor substrate-1 mRNA expression in rat skeletal muscle].

作者信息

Zhang Xu-Zhao, Ying Chen-Jiang, Liu Lie-Gang, Zhang Xi-Ping, Sun Xiu-Fa

机构信息

Department of Nutrition and Food Hygiene, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2004 Sep;38(5):335-8.

PMID:15498251

Abstract

OBJECTIVE

To investigate the molecular mechanism of the effect of alcohol on insulin sensitivity.

METHODS

Four groups of Wistar rats were used, i.e. control (C) group, and low (L), moderate (M) and high (H) alcohol group. Alcohol doses of each group were 0, 0.6, 1.8 and 3.0 ml.(kg.bw)(-1).day(-1). Each group was comprised of 10 male and 10 female rats. Alcohol was given to rats by gastric intubation. Thirteen weeks later, serum was collected for testing of fasting plasma glucose and insulin. HOMA-IR index of each group were calculated. Total muscle RNA was extracted using Trizol Reagent (Promega). The expression level of IRS-1 mRNA in muscle was detected by RT-PCR.

RESULTS

In female rats, the fasting plasma glucose of group (8.36 +/- 0.57) mmol/L was higher and the fasting plasma insulin (15.25 +/- 3.32) was lower than those of group C (7.56 +/- 0.85, 20.80 +/- 3.25). The HOMA-IR of group L (1.775 3 +/- 0.138 1) was lower than that of group C (1.982 6 +/- 0.124 6) (P < 0.05), while IRS-1 mRNA (0.766 1 +/- 0.076 9) was up-regulated (P < 0.05); HOMA-IR of group M (2.202 2 +/- 0.271 0) was higher than that of group C (P < 0.01), while IRS-1 mRNA (0.501 8 +/- 0.049 2) was suppressed (P < 0.01); HOMA-IR of group H (1.850 1 +/- 0.162 8) was not significantly changed as compared with that of group C (1.982 6 +/- 0.124 6) (P > 0.05), while IRS-1 mRNA (0.418 1 +/- 0.049 1) was significantly suppressed (P < 0.01). In male rats, the fasting plasma glucose and insulin had the similar change as those of female rats. The HOMA-IR of group M (1.878 5 +/- 0.250 2) was lower than that of C group (2.147 3 +/- 0.330 8) (P < 0.05), IRS-1 mRNA was up-regulated (0.824 9 +/- 0.064 7) (P < 0.05).

CONCLUSIONS

The present study showed that low-to-moderate dose of alcohol could increase insulin sensitivity; while alcohol abuse could decrease insulin sensitivity. Sex difference in this effect was found. Changes of IRS-1 mRNA expression may be involved in the molecular mechanism of the effects of alcohol on insulin sensitivity.

摘要

目的

探讨酒精影响胰岛素敏感性的分子机制。

方法

采用四组Wistar大鼠，即对照组（C组）以及低剂量（L组）、中剂量（M组）和高剂量（H组）酒精组。每组的酒精剂量分别为0、0.6、1.8和3.0 ml·(kg·bw)⁻¹·d⁻¹。每组由10只雄性和10只雌性大鼠组成。通过胃管给大鼠灌胃酒精。13周后，收集血清检测空腹血糖和胰岛素。计算每组的HOMA-IR指数。使用Trizol试剂（Promega公司）提取肌肉总RNA。通过RT-PCR检测肌肉中IRS-1 mRNA的表达水平。

结果

在雌性大鼠中，L组空腹血糖（8.36±0.57）mmol/L高于C组（7.56±0.85），空腹血浆胰岛素（15.25±3.32）低于C组（20.80±3.25）。L组的HOMA-IR（1.775 3±0.138 1）低于C组（1.982 6±0.124 6）（P<0.05），而IRS-1 mRNA（0.766 1±0.076 9）上调（P<0.05）；M组的HOMA-IR（2.202 2±0.271 0）高于C组（P<0.01），而IRS-1 mRNA（0.501 8±0.049 2）受到抑制（P<0.01）；H组的HOMA-IR（1.850 1±0.162 8）与C组（1.982 6±0.124 6）相比无显著变化（P>0.05），而IRS-1 mRNA（0.418 1±0.049 1）受到显著抑制（P<0.01）。在雄性大鼠中，空腹血糖和胰岛素的变化与雌性大鼠相似。M组的HOMA-IR（1.878 5±0.250 2）低于C组（2.147 3±0.330 8）（P<0.05），IRS-1 mRNA上调（0.824 9±! 0.064 7）（P< ! 0.05）。