摘要
目的 从基因表达水平探讨摄入不同剂量酒精影响胰岛素敏感性的分子机制。方法清洁级Wistar大鼠 80只 ,雌雄各半 ,随机分为对照组和低、中、高剂量组 ,摄入酒精剂量分别为每日 0、0 6、1 8和 3 0ml/kg。给予酒精 13周后 ,测定空腹血糖和血胰岛素 ,计算HOMA胰岛素抵抗指数(HOMA IR)。提取骨骼肌组织总RNA ,通过逆转录 聚合酶链反应测定胰岛素受体底物 1(IRS 1)mRNA表达水平。结果 雌性大鼠 3 0ml/kg组空腹血糖为 (8 36± 0 5 7)mmol/L ,空腹血胰岛素为(15 2 5±3 32 )mIU/L ,0 6ml/kg组HOMA IR为 1 775 3± 0 1381,IRS 1mRNA表达水平为 0 76 6 1± 0 0 76 9;0 8ml/kgHOMA IR为 2 2 0 2 2± 0 2 710 ,IRS 1mRNA表达水平为 0 5 0 18± 0 0 4 92 ;3 0ml/kg组HOMA IR(1 85 0 1± 0 16 2 8)与对照组 (1 982 6± 0 12 4 6 )相比 ,差异无统计学意义 ,IRS 1mRNA表达水平为0 4 181± 0 0 4 91。雄性大鼠 3 0ml/kg组空腹血糖为 (8 12± 0 72 )mmol/L ,空腹血胰岛素为 (18 6 5±4 2 4 )mIU/L ,仅 0 8ml/kg组HOMA I为 (1 8785± 0 2 5 0 2 ) ,IRS 1mRNA表达水平为 0 82 4 9± 0 0 6 4 7。结论 适量酒精摄入可以增强胰岛素敏感性 ,从而降低 2型糖尿病的发病危险。
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-1mRNA (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-1mRNA (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-1mRNA expression may be involved in the molecular mechanism of the effects of alcohol on insulin sensitivity.
出处
《中华预防医学杂志》
CAS
CSCD
北大核心
2004年第5期335-338,共4页
Chinese Journal of Preventive Medicine
基金
国家自然科学基金资助项目 (3 0 170 80 7)