Chronic ethanol feeding impairs glucose tolerance but does not produce skeletal muscle insulin resistance in rat epitrochlearis muscle

Herein, we have investigated whether male Wistar rats develop impaired glucose tolerance after ethanol feeding, Rats were fed a liquid diet providing 35% calories from ethanol (EF) or a control diet that isocalorically replaced ethanol with maltose-dextrins for 4 weeks, Intravenous glucose tolerance was impaired in EF rats compared with pair-fed (PF), but not ad libitum (AL) controls, Areas under the intravenous glucose tolerance test curve were 5476 +/- 516 mm(2), 3056 +/- 421 mm(2), and 4199 +/- 613 mm(2) (p < 0.05) for AL, PF, and EF rats, respectively, Initial plasma insulin concentrations in EF rats were comparable with PF rats; however, 15 min after a dextrose challenge, plasma insulin levels in EF rats were 39% lower than PF mts, Because skeletal muscle is the primary sink for insulin-mediated glucose disposal, the development of skeletal muscle insulin resistance after ethanol feeding could contribute to impaired glucose tolerance. Total GLUT1 was not affected by diet in either red or white muscle. No difference in the total quantity of insulin-responsive glucose transporter, GLUT4, was observed in red muscle, In contrast, GLUT4 was 20% lower in white muscle from EF rats, compared with PF and AL rats. However, insulin-stimulated glucose transport into the epitrochlearis, a white muscle group, was not impaired with ethanol feeding. These data demonstrate that chronic ethanol feeding impairs glucose tolerance; impaired glucose tolerance was associated with an inability to maintain plasma insulin levels, rather than the development of skeletal muscle insulin resistance.