CHRONIC ETHANOL FEEDING IN A HIGH-FAT DIET DECREASES INSULIN-STIMULATED GLUCOSE-TRANSPORT IN RAT ADIPOCYTES

Chronic ethanol feeding in a high-fat diet decreases insulin-stimulate d glucose transport in rat adipocytes. Am. J. Physiol 271 (Endocrinol. Metab. 34): E477-E484, 1996.-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-dependen t diabetes mellitus. We have investigated the long-term effects of eth anol consumption on insulin-regulated glucose transport in rat adipocy tes. Male Wistar rats were fed a high-fat liquid diet containing 35% e thanol (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 stimu late uptake in ethanol-fed rats. Similarly, although okadaic acid incr eased 2-deoxyglucose uptake in pair-fed rats, it had no effect in etha nol-fed rats. GLUT-1 quantity was greater in pair-fed and ethanol-fed rats compared with ad libitum controls. GLUT-4 was decreased in ethano l-fed compared with pair-fed rats but was not different from ad libitu m controls. In ad libitum- and pair-fed rats, insulin increased the tr anslocation of GLUT-4 to the cell surface by 2.0-fold. In contrast, tr anslocation of GLUT-4 was not observed after insulin stimulation of et hanol-fed rats, paralleling the loss of insulin-stimulated glucose upt ake. In ethanol-fed rats, GLUT-4 protein quantity was negatively assoc iated with increased G(s) alpha protein and isoproterenol-stimulated a denosine 3',5'-cyclic monophosphate production. These data suggest tha t loss of insulin-stimulated glucose uptake in rat adipocytes after ch ronic ethanol feeding is at least partially due to decreased movement of GLUT-4 to the cell surface after insulin stimulation.