The diabetogenic effects of excessive ethanol: reducing beta-cell mass, decreasing phosphatidylinositol 3-kinase activity and GLUT-4 expression in rats.
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.
Zhao
Li-Na
LN
Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.
Hao
Li-Ping
LP
Yang
Xue-Feng
XF
Ying
Chen-Jiang
CJ
Yu
Dong
D
Sun
Xiu-Fa
XF
D000428:Alcohol Drinking / Q000009:adverse effects*; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression; D051275:Glucose Transporter Type 4 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D012333:RNA, Messenger; D000431:Ethanol; D019869:Phosphatidylinositol 3-Kinases