Hormonal mechanisms in acute glucose counterregulation: The relative roles of glucagon, epinephrine, norepinephrine, growth hormone, and cortisol

Abstract

The roles of glucagon, catecholamines, cortisol, and growth hormone in acute glucose counterregulation in man were examined by studying the relationship between compensatory changes in glucose production and utilization and increases in the circulating concentrations of these hormones after insulin administration. Restoration of normoglycemia following insulin-induced hypoglycemia was due primarily to a compensatory increase in glucose production; from the known actions of the hormones studied, the time required for the onset of their action, and the time at which increases in their circulating concentrations were observed, only glucagon and the catecholamines could have participated in this compensatory change. Nevertheless, growth hormone and cortisol as well as the catecholamines could have contributed to restoration of normoglycemia in a subsidiary manner by accelerating the return of glucose utilization to basal rates. These potential roles for glucagon, catecholamines, growth hormone, and cortisol were examined by studying the effects of pharmacologically- or surgically-induced conditions in which increases in the circulating levels of these hormones (or the consequences thereof) were not possible following insulin-induced hypoglycemia: isolated glucagon deficiency (infusion of somatostatin plus growth hormone) blunted the compensatory increase in glucose production and impaired restoration of normoglycemia. Neither isolated growth hormone deficiency (infusion of somatostatin plus glucagon), adrenergic blockade (infusion of phentolamine and propranolol), nor adrenalectomy influenced compensatory changes in glucose turnover or affected restoration of normoglycemia. Superimposition of growth hormone deficiency upon glucagon deficiency (infusion of somatostatin without hormone replacement) did not exacerbate the effect of isolated glucagon deficiency. However, glucagon deficiency in the presence of either adrenalectomy or adrenergic blockade caused further impairment in restoration of normoglycemia compared to that observed with isolated glucagon deficiency. The results of these studies thus indicate that the major acute glucose counterregulatory hormones in man are glucagon and catecholamines. During recovery of plasma glucose from insulin-induced hypoglycemia, increases in plasma glucagon, but not in plasma cortisol and growth hormone, are essential for normal glucose counterregulation. Adrenergic mechanisms, specifically adrenomedullary epinephrine, become critical to recovery from hypoglycemia when glucagon secretion is impaired.