Some explanations for species differences in hyperglycemic responses to adrenergic agents

There are species differences in the metabolic responses to catecholamines and their antagonists. In one group (dog, cat) isoproterenol equals or surpasses the potency of epinephrine for increasing plasma glucose and propranolol and other β-adrenergic antagonists in moderate doses suppress these responses. In the second group (rat, rabbit, baboon, human) isoproterenol is considerably less potent than epinephrine for increasing plasma glucose and for reducing liver glycogen and the β-adrenergic antagonists are poor inhibitors of epinephrine-induced hyperglycemia or liver glycogen depletion. In all these species isoproterenol is more potent than epinephrine for increasing muscle glycogenolysis and plasma lactic acid and these effects are sensitive to inhibition by β-adrenergic antagonists. The adrenergic receptors involved in the activation of hepatic glucose release by epinephrine in rats and rabbits differ from those in the dog. In rats and rabbits evidence has been obtained which implicates the release of insulin by isoproterenol as an important factor in limiting the hyperglycemic response to isoproterenol. Alloxan-diabetic rats and rabbits, radioimmunoassay of insulin and glucagon, and the use of somatostatin as an inhibitor of glucagon and insulin release have been applied to produce the evidence which implicates glucagon release as a large factor in the epinephrine-induced hyperglycemia and hepatic glycogenolysis in the rat, rabbit and baboon, but not in the dog.