TY - JOUR
T1 - Effect of physiological hyperinsulinemia on counterregulatory hormone responses during hypoglycemia in humans
AU - Mellman, Michael J.
AU - Davis, Maris R.
AU - Shamoon, Harry
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1992/11
Y1 - 1992/11
N2 - We evaluated the effect of continuous physiological hyperinsulinemia on counterregulatory hormone responses in seven healthy subjects, each studied on two occasions. Hormone responses were measured during identical 2-h periods of hypoglycemia (plasma glucose target 3.5 mmol/L) at insulin levels of 350 pmol/L or 640 pmol/L. During hypoglycemia, there were significant (50-1400%) increases in glucagon, epinephrine, norepinephrine, GH, and cortisol which were comparable in the two groups. We further evaluated the influence of the duration of mild hyperinsulinemia on the responses in an additional group of normal subjects (n = 7). Brief (30 min) exposure to insulin was compared to a prolonged (3.5 h) insulin infusion, each followed by identical hypoglycemia. Plasma insulin (approximately 350 pmol/L) and plasma glucose (target 3.3 mmol/L) were similar in both groups. The increases in epinephrine, norepinephrine, GH, and cortisol during hypoglycemia were virtually identical in the two groups. However, the secretion of glucagon was blunted following prolonged hyperinsulinemia, increasing to levels of 249 ± 17 ng/L in the brief studies and to only 185 ± 20 ng/L in the prolonged studies (P < 0.005). The insulin-induced decrement in plasma amino acids were similar in the two studies and could not account for the impaired glucagon secretory response. Conclusions: 1) Brief exposure to even high physiological levels of insulin do not alter the magnitude of counterregulatory hormone secretion during hypoglycemia; 2) prolonged hyperinsulinemia results in a selective blunting of the plasma glucagon response to hypoglycemia, perhaps due to a direct suppressive effect of insulin on alpha-cell secretion.
AB - We evaluated the effect of continuous physiological hyperinsulinemia on counterregulatory hormone responses in seven healthy subjects, each studied on two occasions. Hormone responses were measured during identical 2-h periods of hypoglycemia (plasma glucose target 3.5 mmol/L) at insulin levels of 350 pmol/L or 640 pmol/L. During hypoglycemia, there were significant (50-1400%) increases in glucagon, epinephrine, norepinephrine, GH, and cortisol which were comparable in the two groups. We further evaluated the influence of the duration of mild hyperinsulinemia on the responses in an additional group of normal subjects (n = 7). Brief (30 min) exposure to insulin was compared to a prolonged (3.5 h) insulin infusion, each followed by identical hypoglycemia. Plasma insulin (approximately 350 pmol/L) and plasma glucose (target 3.3 mmol/L) were similar in both groups. The increases in epinephrine, norepinephrine, GH, and cortisol during hypoglycemia were virtually identical in the two groups. However, the secretion of glucagon was blunted following prolonged hyperinsulinemia, increasing to levels of 249 ± 17 ng/L in the brief studies and to only 185 ± 20 ng/L in the prolonged studies (P < 0.005). The insulin-induced decrement in plasma amino acids were similar in the two studies and could not account for the impaired glucagon secretory response. Conclusions: 1) Brief exposure to even high physiological levels of insulin do not alter the magnitude of counterregulatory hormone secretion during hypoglycemia; 2) prolonged hyperinsulinemia results in a selective blunting of the plasma glucagon response to hypoglycemia, perhaps due to a direct suppressive effect of insulin on alpha-cell secretion.
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U2 - 10.1210/jcem.75.5.1430091
DO - 10.1210/jcem.75.5.1430091
M3 - Article
C2 - 1430091
AN - SCOPUS:0026482532
VL - 75
SP - 1293
EP - 1297
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 5
ER -