Effects of in vivo and in vitro Alcohol Administration on Insulin Binding and Glycogenesis in Isolated Rat Hepatocytes

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Abstract
Chronic alcohol ingestion was accompanied by a mild decrease in insulin binding (from 11.7 to 8.9% per 1 × 106 cells) that was accounted for by changes in the dissociation constant of insulin’s binding sites. The basal rate of 14C-glucose incorporation into glycogen was reduced both in alcoholic and pair-fed animals. Insulin stimulated 14C-glucose incorporation into glycogen in control (72% above basal rate) and pair-fed (76% above basal rate) animals. In contrast, only a minimal stimulation of glucose incorporation into glycogen (30%) induced by insulin was observed in alcoholic animals. Hepatocyte responsiveness to insulin was restored when the animals were switched back to normal dry food diet. When the hepatocytes were incubated with 50 mM alcohol for 1 h at 37 °C (in vitro experiments) insulin binding remained unchanged. There was a mild but significant decrease in insulin’s ability to enhance glucose incorporation into glycogen. The anti-catabolic effect of insulin was unaffected by alcohol. In summary, chronic alcohol ingestion causes significant but reversible changes in post-receptor events of insulin’s action.