Ethanol inhibits insulin action on lipolysis and on insulin release in elderly men

We have studied effects of ethanol on insulin's ability to suppress its own release and on its antilipolytic action in 12 healthy elderly men during euglycemic hyperinsulinemia. Insulin secretion was estimated from plasma C-peptide concentrations. Lipolysis was determined with the two stable isotopes [2H5]glycerol and [1-13C]palmitate. Hyperinsulinemia (approximately 350 pM) decreased plasma C-peptide by approximately 60% (from 325 to 122 pM, P < 0.05). Ethanol (approximately 10 mM) completely prevented the fall in C-peptide concentration. Ethanol decreased the antilipolytic action of insulin by approximately 40% [with insulin alone, glycerol rate of appearance (Ra) decreased from 1.8 to 0.6 mumol.kg-1 x min-1; with insulin + ethanol, it only decreased from 1.8 to 1.1 mumol.kg-1 x min-1]. Ethanol did not affect palmitate Ra, which fell from 1.4 to 0.6 mumol.kg-1 x min-1 with insulin and from 1.4 to 0.3 mumol.kg-1 x min-1 with insulin plus ethanol. Fatty acid reesterification was not affected by insulin but tripled (from 0.6 to 1.9 mumol.kg-1 x min-1) in response to insulin plus ethanol. Our data showed that modest concentrations of ethanol suppressed the inhibitory actions of insulin on its own release and on lipolysis. The inhibition by ethanol of various insulin actions, including glucose disposal, lipolysis, and insulin release, in diverse tissues such as muscle, adipose tissue, and pancreas raises the possibility that ethanol may produce a state of generalized insulin resistance.