Interaction of glucocorticoids with glucagon and epinephrine in the control of gluconeogenesis and glycogenolysis in liver and of lipolysis in adipose tissue.

The effects of glucagon and epinephrine on gluconeogenesis and glycogenolysis in liver and of catecholamines and adrenocorticotrophic hormone on lipolysis in adipose tissue were examined in normal and adrenalectomized rats. Glucagon or epinephrine stimulation of glucose synthesis from lactate was markedly reduced in isolated perfused livers from fasted, adrenal-deficient rats. Administration in uiuo of the glucocorticoid dexamethasone 30 min prior to perfusion restored the gluconeogenic response to glucagon. Cortisol and dexamethasone were also effective when added to the perfusion medium, but had no effect in the absence of glucagon. Cyclic AMP (adenosine 3’ ,5’-monophosphate) accumu.lation was normal or increased in livers from adrenalectomized rats perfused without hormones or with glucagon or epinephrine. Gluconeogenesis in livers from fasted, adrenal-deficient rats was relatively unresponsive to cyclic AMP or dibutyryl cyclic AMP added to the perfusion medium. Hypophysectomized rats also showed an impairment of cyclic AMP activation of gluconeogenesis which was corrected by treatment with cortisol but not growth hormone. High concentrations of epinephrine, glucagon, and cyclic AMP stimulated glucose production and lactate gluconeogenesis in livers from fed, adrenalectomized rats. However, more nearly physiological concentrations of the hormones did not activate glucose release and phosphorylase normally in such livers. Livers from fed, adrenalectomized rats also showed diminished activation of gluconeogenesis and phosphorylase by exogenous cyclic AMP. Omission of Ca+f from the perfusion medium did not alter control or cyclic AMP-stimulated glycogenolysis or gluconeogenesis in normal rats. Addition of ethyleneglycol-bis