Contribution of cortisol to glucose counterregulation in humans.
To test the hypothesis that cortisol secretion plays a counterregulatory role in hypoglycemia in humans, four studies were performed in eight normal subjects. In all studies, insulin (15 mU.m-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 1 microU/ml). In study 1, plasma glucose concentration and glucose fluxes [( 3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored, and plasma glucose decreased from 89 +/- 2 to 52 +/- 2 mg/dl for 12 h. In study 2, (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretion (except for catecholamines) was prevented by somatostatin (0.5 mg/h, iv) and metyrapone (0.5 g/4 h, per os), and glucagon, cortisol, and growth hormone were infused to reproduce the concentrations of study 1. In study 3 (lack of cortisol increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma cortisol at basal levels, and glucose was infused, whenever needed, to reproduce plasma glucose concentration of study 2. Study 4 was identical to study 3, but exogenous glucose was not infused. Isolated lack of cortisol increase caused a approximately 22% decrease in hepatic glucose production (P less than 0.01) and a approximately 15% increase in peripheral glucose utilization (P less than 0.01), which resulted in greater hypoglycemia (37 +/- 2 vs. 52 +/- 2 mg/dl, P less than 0.01) despite compensatory increases in plasma epinephrine. Lack of cortisol response also reduced plasma free fatty acid, beta-hydroxybutyrate, and glycerol concentrations approximately 50%. We conclude that cortisol normally plays an important counterregulatory role during hypoglycemia by augmenting glucose production, decreasing glucose utilization, and accelerating lipolysis.
De Feo
P
P
Istituto di Patologia Medica, Università di Perugia, Italy.
Perriello
G
G
Torlone
E
E
Ventura
M M
MM
Fanelli
C
C
Santeusanio
F
F
Brunetti
P
P
Gerich
J E
JE
Bolli
G B
GB
D020155:3-Hydroxybutyric Acid; D000328:Adult; D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005990:Glycerol / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000502:physiology*; D006885:Hydroxybutyrates / Q000097:blood; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007700:Kinetics; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D011169:Portal Vein
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D013006:Growth Hormone; D005934:Glucagon; D000409:Alanine; D005990:Glycerol; D020155:3-Hydroxybutyric Acid; D006854:Hydrocortisone; D004837:Epinephrine