Gluconeogenesis in rabbit liver. IV. The effects of glucagon, epinephrine, alpha- and beta-adrenergic agents on gluconeogenesis and pyruvate kinase in hepatocytes given dihydroxyacetone or fructose

Abstract

1. Epinephrine, isoproterenol and phenylephrine each increases significantly gluconeogenesis (from dihydroxy-acetone or D-fructose) and glycogenolysis when added to hepatocytes from 48-h fasted rabbits. Such stimulation of both processes by epinephrine, isoproterenol or phenylephrine is negated by the beta-adrenergic antagonist propranolol but remains significant in the presence of the alpha-adrenergic antagonist phentolamine. Conversely, previous data suggest that catecholamine-induced stimulation of glucose formation from L-lactate is both alpha- and beta-adrenergic-sensitive. 2. Glucagon, epinephrine, isoproterenol, phenylephrine and dibutyryl cyclic AMP each inhibits significantly pyruvate kinase activity in rabbit hepatocytes. Inhibition of pyruvate kinase activity by epinephrine, isoproterenol or phenylephrine is negated by propranolol but insensitive to phentolamine. 3. These observations suggest that enhancement by epinephrine of glucose formation from either dihydroxyacetone or D-fructose is solely beta-adrenergic-regulated, just as is its inhibition of pyruvate kinase activity. Stimulation of gluconeogenesis by glucagon, epinephrine, isoproterenol, phenylephrine or dibutyryl cyclic AMP may be at least in part directly related to their ability to inhibit pyruvate kinase.