Interrelationships between the metabolic effects of glucagon and ethanol in the perfused mouse liver

Effects of glucagon and ethanol on hepatic metabolism were examined with in situ perfused livers from fasted Swiss albino mice. In the absence of added gluconeogenic substrate, the presence of glucagon with ethanol effectively restored hepatic glucose production to a rate found with livers perfused with the hormone alone. When lactate was added to the perfusate, the presence of ethanol almost completely suppressed glucose formation but glucagon only partially overcame this inhibition. Ethanol and/or glucagon inhibited hepatic alpha-amino acid N release both in the absence and presence of added gluconeogenic substrate. Ketone body formation was increased three-fold when both glucagon and ethanol were added together to the medium of livers perfused in the absence of exogenous gluconeogenic precursor, yet neither agent alone had an effect. Ethanol utilization by the perfused liver was markedly inhibited by glucagon in the absence of added lactate. The presence of exogenous lactate also decreased ethanol removal by the liver and the addition of glucagon with lactate diminished ethanol clearance further. Thus, interrelationships between the consequences of glucagon and ethanol on hepatic metabolism have been delineated in the perfused mouse liver.