Regulation of glucose metabolism by sympathochromaffin catecholamines

The catecholamines, including epinephrine secreted predominantly from the adrenal medullae and norepinephrine released predominantly from sympathetic postganglionic neurons, have long been known to exert potent metabolic effects. However, the roles of sympathochromaffin system in the regulation of human intermediary metabolism are only beginning to emerge. The mechanisms of the hyperglycemic effect of the catecholamines are complex. Normally they involve both direct and indirect (hormone-mediated) actions, are the result of both stimulation of glucose production and limitation of glucose utilization, and are mediated through both β- and α-adrenergic receptors in humans. Epinephrine plays a secondary role in glucose counterregulation. It is not normally critical, but it compensates and becomes critical to the prevention or correction of hypoglycemia when glucagon is deficient or, perhaps, when hypoglycemia is severe. Catecholamines, probably sympathetic neural norepinephrine, play a primary role in the prevention of hypoglycemia during exercise. Some patients with insulin-dependent diabetes mellitus (IDDM) develop deficient epinephrine responses to plasma glucose decrements along with deficient glucagon responses. This combination results in defective glucose counterregulation with a substantially increased risk of severe iatrogenic hypoglycemia. Thus, the sympathochromaffin system is particularly important to such patients. Catecholamines are involved in the pathogenesis of posthypoglycemic hyperglycemia, and perhaps in that of stress hyperglycemia, in patients with IDDM, but they are not critical to development of the dawn phenomenon. Much has been learned about the metabolic roles of the sympathochromaffin system, especially as they relate to the regulation of glucose metabolism, in recent years. Given the investigative tools available and in development, it is likely that this accelerated rate of progress will continue. Further insight into the metabolic physiology of the sympathochromaffin system, at levels ranging from basic to applied, can be expected to permit further insight into the metabolic pathophysiology of the system, and its clinical relevance.