ALCOHOL AND GLUCOSE-METABOLISM IN SKELETAL-MUSCLES IN THE RAT

Ethanol is known to cause an acute and profound insulin resistance in man and the rat primarily via effects on glucose utilization. This pap er examines the nature of these inhibitory effects on whole-body gluco se utilization using the euglycaemic hyperinsulinaemic clamp in the co nscious unrestrained rat. We confirm that ethanol infusion causes an a cute insulin resistance, the rate of glucose infusion required to main tain euglycaemia (GIR) being decreased markedly by ethanol. To ensure that the GIR is a measure of whole-body glucose disposal, glucose turn over and hepatic glycogen levels were measured. These studies showed t hat ethanol totally suppressed hepatic glucose production. The reducti on in GIR is associated with marked decreases in glucose uptake and gl ycogen synthesis in most skeletal muscles. In oxidative but not in non -oxidative muscles, the activation of glycogen synthase in response to insulin was decreased by ethanol, suggesting that a defect in glycoge n synthase activation may be responsible for the decrease in glycogen synthesis. The basis of the inhibitory effects of ethanol on insulin-s timulated glucose metabolism in muscle is unknown, but may involve mem brane-associated impairments in insulin signalling and/or the glucose transport system.