Chronic ethanol feeding in a high-fat diet decreases insulin-stimulated glucose transport in rat adipocytes.
Ethanol consumption has been associated with glucose intolerance and insulin resistance and is suggested to be an independent risk factor in the development of non-insulin-dependent diabetes mellitus. We have investigated the long-term effects of ethanol consumption on insulin-regulated glucose transport in rat adipocytes. Male Wistar rats were fed a high-fat liquid diet containing 35% ethanol (ethanol fed) or a control diet that isocalorically substituted maltose dextrin for ethanol (ad libitum). A third group was pair fed the control diet. Basal rates of 2-deoxyglucose uptake were similar in adipocytes from all three groups. Treatment with insulin increased 2-deoxyglucose uptake in ad libitum- and pair-fed rats but did not stimulate uptake in ethanol-fed rats. Similarly, although okadaic acid increased 2-deoxyglucose uptake in pair-fed rats, it had no effect in ethanol-fed rats. GLUT-1 quantity was greater in pair-fed and ethanol-fed rats compared with ad libitum controls. GLUT-4 was decreased in ethanol-fed compared with pair-fed rats but was not different from ad libitum controls. In ad libitum- and pair-fed rats, insulin increased the translocation of GLUT-4 to the cell surface by 2.0-fold. In contrast, translocation of GLUT-4 was not observed after insulin stimulation of ethanol-fed rats, paralleling the loss of insulin-stimulated glucose uptake. In ethanol-fed rats, GLUT-4 protein quantity was negatively associated with increased Gs alpha protein and isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate production. These data suggest that loss of insulin-stimulated glucose uptake in rat adipocytes after chronic ethanol feeding is at least partially due to decreased movement of GLUT-4 to the cell surface after insulin stimulation.
Wilkes
J J
JJ
Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario, Canada.
DeForrest
L L
LL
Nagy
L E
LE
D017667:Adipocytes / Q000378:metabolism*; D000428:Alcohol Drinking; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004041:Dietary Fats / Q000008:administration & dosage*; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D004041:Dietary Fats; D007328:Insulin; D005947:Glucose