Gluconeogenesis in rabbit liver. III. The influences of glucagon, epinephrine, alpha- and beta-adrenergic agents on gluconeogenesis in isolated hepatocytes.
1. Gluconeogenesis from various substrates has been demonstrated in hepatocytes from 48 h fasted rabbits. Maximum rates of gluconeogenesis (expressed as mumol glucose formed/30 min per 10(8) cells) are: D-fructose, 9.86; dihydroxyacetone, 5.28; L-lactate, 5.26; L-lactate/pyruvate, 3.83; pyruvate, 3.32; glycerol, 2.92; L-alanine, 2.24. 2. Gluconeogenesis from L-lactate is enhanced 1.3--1.5-fold over control values by glucagon, L-epinephrine, L-norepinephrine, dibutyryl cyclic AMP, L-phenylephrine and L-isoproterenol. Glucogenesis from both dihydroxyacetone and D-fructose is stimulated 1.7--2.0-fold of control values by glucagon, epinephrine and dibutyryl cyclic AMP. 3. Gluconeogenesis from lactate is enhanced by both alpha- and beta-adrenergic stimulations based on findings with alpha- and beta-agonists and antagonists. 4. Enhancement of gluconeogenesis by epinephrine and norepinephrine is apparently due to both alpha- and beta-adrenergic effects, as either propranolol or phentolamine partially inhibits such enhancement. The consistently more pronounced inhibition produced by propranolol implies that stimulation of glucose formation by catecholamines is more strongly beta-adrenergic related. Epinephrine-induced glycogenolysis in rabbit hepatocytes is severely inhibited by propranolol but insensitive to phentolamine, suggesting that glycogen breakdown is solely beta-adrenergic related. These observations contrast with those of others that stimulation of both gluconeogenesis and glycogenolysis by catecholamines while sensitive to both alpha- and beta-adrenergic stimulation in rats, at least young rats, is primarily alpha-adrenergic mediated, especially in adult rats.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits
D010656:Phenylephrine; D003994:Bucladesine; D005934:Glucagon; D011433:Propranolol; D007545:Isoproterenol; D004837:Epinephrine; D010646:Phentolamine