Genetic analyses of ethanol-induced hyperglycemia.

Abstract

Genetic sensitivity to ethanol-induced hyperglycemia was hypothesized to be related to sensitivity to ethanol-induced hypothermia and conditioned taste aversion. These hypotheses were explored by characterizing blood glucose changes after ethanol exposure in BXD recombinant inbred mice. Adult male and female BXD recombinant inbred mice were acutely exposed to 4 g/kg of ethanol or saline with the order of exposure counterbalanced, and separated by a 1-week interval. Tail blood samples and rectal temperatures were determined immediately before ethanol/saline exposure and 2 hr after exposure. Substantial strain differences in ethanol-induced hyperglycemia and hypothermia were noted. In addition, sex also determined sensitivity to ethanol-induced hyperglycemia and interacted with strain. Correlational analyses using strain means indicated that ethanol-induced hyperglycemia was genetically independent from ethanol-induced hypothermia or conditioned taste aversion. Quantitative trait locus (QTL) analyses indicated provisional QTL for ethanol-induced hyperglycemia on chromosomes 1, 3, 4, 6, 7, 9, 12, 14, and 18, which, in part, were sex specific. These findings indicate important sex differences in the glycemic response to ethanol. In addition, multiple genes likely control this response, independent from genes that are important for the thermic or aversive effects of ethanol.