Alcohol Suppresses Meal-Induced Insulin Sensitization

Abstract

In the fed state, the glucose disposal action of insulin can be attributed in approximately equal part to the direct action of insulin and to a hepatic insulin sensitizing substance (HISS) that acts selectively on skeletal muscle. HISS action is absent in the 24-hour fasted state. The objective of this study was to determine whether alcohol administered with a meal affected meal-induced insulin sensitization (MIS). Rats were fasted for 24 hours and anesthetized, and insulin sensitivity was evaluated using the rapid insulin sensitivity test (RIST). A liquid mixed meal was injected into the stomach along with diluted alcohol equivalent to 1, 0.25, and 0.125 mL/kg of ethanol. After 90 minutes, a second RIST was carried out, atropine administered, and a third RIST done. A control fed group received no ethanol and a RIST was determined at 90 minutes; then 1 mL/kg ethanol or water was administered and the RIST was tested 1 hour later. Ethanol co-administered with a meal produced a dose-dependent suppression of MIS. MIS was blocked back to fasting levels by atropine. MIS developed to a maximal level by 90 minutes and was maintained for at least 1 hour more. Ethanol (1 mL/kg) administered after MIS was fully developed resulted in complete suppression of insulin sensitivity back to a fasting level. MIS can be demonstrated in response to gastric administration of a liquid mixed meal in anesthetized rats. Alcohol produces a dose-related suppression of MIS and can completely reverse MIS once it has been developed. The concentrations of alcohol reached were well within levels attained by social drinkers. MIS was confirmed to act through HISS action, and neither MIS nor alcohol affected the HISS-independent component of insulin action.