Hormonal mechanisms of recovery from insulin-induced hypoglycemia in man

Mechanisms for recovery of plasma glucose from acute insulin-induced hypoglycemia were investigated in normal and adrenalectomized human subjects with somatostatin used to inhibit glucagon and growth hormones secretion. In normal subjects with glucagon and growth hormone deficiency, infusion of somatostatin enhanced insulin-induced plasma glucose decrements and attenuated restitution of normoglycemia despite augmented plasma cortisol, epinephrine, and norepinephrine responses; these effects were prevented by simultaneous infusion of somatostatin with glucagon (subjects with growth hormone deficiency) but not with growth hormone (subjects with glucagon deficiency). In adrenalectomized subjects receiving glucocorticoid replacement (epinephrine deficiency), plasma glucose responses after insulin administration were not significantly different from those of normal subjects; however, somatostatin infusion (epinephrine, glucagon, and growth hormone deficiency) enhanced insulin-induced hypoglycemia more in these subjects than in the normal subjects and completely abolished restitution of normoglycemia. These studies indicate that glucagon plays a primary role and epinephrine a secondary role in recovery of plasma glucose from acute insulin-induced hypoglycemia in man, and provide no support for immediate contributions of growth hormone, cortisol, or neurally released norepinephrine.