Tomie Furuya Daniela, Binsack Ralf, Onishi Mary Emy, Monteiro Seraphim Patricia, Fabres Machado Ubiratan
Dept. of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo. Av. Prof. Lineu Prestes 1524, 05508-900 Sao Paulo, Brazil.
Life Sci. 2005 Aug 26;77(15):1813-24. doi: 10.1016/j.lfs.2004.12.046.
Moderate amounts of alcohol intake have been reported to have a protective effect on the cardiovascular system and this may involve enhanced insulin sensitivity. We established an animal model of increased insulin sensitivity by low ethanol consumption and here we investigated metabolic parameters and molecular mechanisms potentially involved in this phenomenon. For that, Wistar rats have received drinking water either without (control) or with 3% ethanol for four weeks. The effect of ethanol intake on insulin sensitivity was analyzed by insulin resistance index (HOMA-IR), intravenous insulin tolerance test (IVITT) and lipid profile. The role of liver was investigated by the analysis of insulin signaling pathway, GLUT2 gene expression and tissue glycogen content. Rats consuming 3% ethanol showed lower values of HOMA-IR and plasma free fatty acids (FFA) levels and higher hepatic glycogen content and glucose disappearance constant during the IVITT. Neither the phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), nor its association with phosphatidylinositol-3-kinase (PI3-kinase), was affected by ethanol. However, ethanol consumption enhanced liver IRS-2 and protein kinase B (Akt) phosphorylation (3 times, P<0.05), which can be involved in the 2-fold increased (P<0.05) hepatic glycogen content. The GLUT2 protein content was unchanged. Our findings point out that liver plays a role in enhanced insulin sensitivity induced by low ethanol consumption.
据报道，适量饮酒对心血管系统具有保护作用，这可能与胰岛素敏感性增强有关。我们通过低剂量乙醇摄入建立了胰岛素敏感性增强的动物模型，并在此研究了可能参与此现象的代谢参数和分子机制。为此，将Wistar大鼠分为两组，一组饮用不含乙醇的饮用水（对照组），另一组饮用含3%乙醇的饮用水，持续四周。通过胰岛素抵抗指数（HOMA-IR）、静脉胰岛素耐量试验（IVITT）和血脂谱分析乙醇摄入对胰岛素敏感性的影响。通过分析胰岛素信号通路、GLUT2基因表达和组织糖原含量来研究肝脏的作用。饮用3%乙醇的大鼠在IVITT期间HOMA-IR值和血浆游离脂肪酸（FFA）水平较低，肝糖原含量较高，葡萄糖消失常数较高。乙醇对胰岛素受体（IR）和胰岛素受体底物-1（IRS-1）的磷酸化及其与磷脂酰肌醇-3激酶（PI3-激酶）的结合均无影响。然而，乙醇摄入增强了肝脏IRS-2和蛋白激酶B（Akt）的磷酸化（3倍，P<0.05），这可能与肝糖原含量增加2倍（P<0.05）有关。GLUT2蛋白含量未发生变化。我们的研究结果表明，肝脏在低剂量乙醇摄入诱导的胰岛素敏感性增强中发挥作用。
