Epinephrine, Norepinephrine, Glucagon, and Growth Hormone Release in Association with Physiological Decrements in the Plasma Glucose Concentration in Normal and Diabetic Man*

TLDR

Physiological reductions in plasma glucose (95→60 mg/dl) activate counter‑regulatory hormones, suggesting a role in non‑hypoglycemic glucose regulation and hypoglycemia prevention. The study used a Biostator to induce controlled glucose declines from 95 to 60 mg/dl in 10 subjects (5 normal, 5 diabetic) and from 200 to 100 mg/dl in 6 subjects (3 normal, 3 diabetic) while measuring epinephrine, norepinephrine, glucagon, GH, and cortisol. Early rises in epinephrine, norepinephrine, and glucagon, with a later GH increase, occurred with physiological glucose drops; larger decrements produced smaller but significant hormone responses, revealing no absolute glucose threshold and an inverse relationship between glucose level and counter‑regulatory magnitude, with similar patterns in diabetic and nondiabetic groups.

Abstract

The release of potentially important glucose counter-regulatory factors (epinephrine, norepinephrine, glucagon, GH, and cortisol) was studied during Biostator-controlled reductions in the plasma glucose concentration from the high physiological level of 95 mg/dl to the low physiological level of 60 mg/dl in 10 subjects (5 normal subjects and 5 patients with insulin-dependent diabetes) and from the supraphysiological level of 200 to 100 mg/dl in 6 subjects (3 normal subjects and 3 patients with insulin-dependent diabetes). Reductions in the plasma glucose concentration from 95 to 60 mg/dl were associated with early (+30 to +40 min) increments [here with the maximal values expressed as the percent of the mean baseline (mean ± SE)] in plasma epinephrine (529 ± 144; P < 0.02), norepinephrine (146 ± 12; P < 0.01), and glucagon (123 ± 13; P < 0.05) and a late (+75 min) increment in plasma GH (2504 ± 1065; P < 0.05); an apparent late (+105 min) increment in plasma cortisol (132 ± 15) was not statistically significant. Reductions of the plasma glucose concentrations from 200 to 100 mg/dl were associated with smaller, but significant, increments in plasma epinephrine, norepinephrine, glucagon, and GH, an observation confirmed by study of additional normal subjects. Other than the fact that the nondiabetic group, but not the diabetic group, exhibited significant increments in plasma glucagon, systematic differences between patients with diabetes and subjects without diabetes were not detected. Thus, there is not an absolute plasma glucose concentration threshold for activation of glucose counter-regulatory systems, and neither the absolute decrement in the plasma glucose concentration nor the initial rate of decline in the plasma glucose concentration appears to be the primary determinant of the magnitude of the counter-regulatory response. Rather, there appears to be a quantitative spectrum of counter-regulatory responses to decrements in the plasma glucose concentrationsuch that the magnitude of the counter-regulatory response is inversely related to the absolute plasma glucose concentration. Further, in view of their activation with physiological decrements (95 to 60 mg/dl) in the plasma glucose concentration, one or more of these potentially important glucose counter-regulatory systems may play a physiological role in nonhypoglycemic glucose counter-regulation and the prevention of hypoglycemia.