Epinephrine supports the postabsorptive plasma glucose concentration and prevents hypoglycemia when glucagon secretion is deficient in man.

Abstract

We hypothesized that adrenergic mechanisms support the postabsorptive plasma glucose concentration, and prevent hypoglycemia when glucagon secretion is deficient. Accordingly, we assessed the impact of glucagon deficiency, produced by infusion of somatostatin with insulin, without and with pharmacologic alpha- and beta-adrenergic blockade on the postabsorptive plasma glucose concentration and glucose kinetics in normal human subjects. During somatostatin with insulin alone mean glucose production fell from 1.5 +/- 0.05 to 0.7 +/- 0.2 mg/kg per min and mean plasma glucose declined from 93 +/- 3 to 67 +/- 4 mg/dl over 1 h; glucose production then increased to base-line rates and plasma glucose plateaued at 64-67 mg/dl over 2 h. This plateau was associated with, and is best attributed to, an eightfold increase in mean plasma epinephrine. It did not occur when adrenergic blockade was added; glucose production remained low and mean plasma glucose declined progressively to a hypoglycemic level of 45 +/- 4 mg/dl, significantly (P less than 0.001) lower than the final value during somatostatin with insulin alone. These data provide further support for the concept that maintenance of the postabsorptive plasma glucose concentration is a function of insulin and glucagon, not of insulin alone, and that adrenergic mechanisms do not normally play a critical role. They indicate, however, that an endogenous adrenergic agonist, likely adrenomedullary epinephrine, compensates for deficient glucagon secretion and prevents hypoglycemia in the postabsorptive state in humans. Thus, postabsorptive hypoglycemia occurs when both glucagon and epinephrine are deficient, but not when either glucagon or epinephrine alone is deficient, and insulin is present.