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  • Title: The diabetogenic effects of excessive ethanol: reducing beta-cell mass, decreasing phosphatidylinositol 3-kinase activity and GLUT-4 expression in rats.
    Author: Zhao LN, Hao LP, Yang XF, Ying CJ, Yu D, Sun XF.
    Journal: Br J Nutr; 2009 May; 101(10):1467-73. PubMed ID: 18959809.
    Abstract:
    The diabetogenic impact of ethanol remains as a focal point of basic and clinical investigations. In this study, Wistar rats were subjected to daily intragastric ethanol administration (10 ml/kg body weight injection with 0 (control), 10, 20 and 33 % (v/v) ethanol in the injections, respectively) for 19 weeks. At the end of the administration, we found that the fasting plasma glucose level of the 33 % (v/v) ethanol-loaded group was 18 % higher than the control. Insulin sensitivity was decreased in a dose-dependent manner in all the ethanol-loaded groups (r - 0.842, P < 0.001) during intraperitoneal insulin tolerance test. Necrotic/haemorrhagic injury was detected in the pancreas and islet beta-cell mass was significantly reduced in the 33 % (v/v) ethanol-loaded rats by immunohistochemical and morphometric analysis. At the molecular level, we detected a dose-dependent attenuation of phosphatidylinositol 3-kinase activity (r - 0.956, P < 0.001) and GLUT-4 expression (GLUT-4 mRNA, r - 0.899, P < 0.001; GLUT-4 protein, r - 0.964, P < 0.001) in skeletal muscle. These results demonstrated that drinking is a conditional aetiological factor for diabetes and excessive ethanol intake is negatively associated with both insulin sensitivity and beta-cell mass. The whole-body insulin resistance might result from the ethanol-induced insulin signalling defects in muscle.
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