In order to further elucidate the potentiating effect of ethanol on the glucose-mediated insulin response, triply catheterized anesthetized pigs were submitted to an intravenous glucose infusion test after a four-hour preinfusion with ethanol (11 pigs) or saline (six pigs, control experiment). During the tests portal, hepatic, and peripheral venous blood was drawn simultaneously. Two series of ethanol-preinfusion experiments were carried out: in one series the serum ethanol concentration was maintained at ∼ 10 mM and in the other at 19 mM. Compared with saline, 10 mM of serum ethanol induced a more than threefold increment in the insulin secretory response to glucose as estimated in the portal blood (p < 0.01). Likewise, hepatic and peripheral venous blood insulin levels were enhanced (p < 0.01). In contrast, 19 mM of serum ethanol did not elevate serum insulin levels above those found in the control experiments. When individual incremental portal insulin areas were plotted against the corresponding average value of serum ethanol in the preinfusion period, a significant inverse relationship was found (p < 0.02), indicating a decrease in the potentiating effect of ethanol on the glucose-mediated insulin response with increasing levels of serum ethanol. Comparison of portal and hepatic incremental insulin areas revealed that ethanol did not, in the concentration range investigated, influence the hepatic insulin degradation rate. In conclusion, ethanol seems to potentiate, in an inverse concentration-dependent manner, the glucose-mediated insulin response through an action directly on the pancreas.

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