Demonstration of a role for growth hormone in glucose counterregulation.
To test the hypothesis that growth hormone secretion plays a counterregulatory role in prolonged hypoglycemia in humans, four studies were performed in nine normal subjects. Insulin (15 mU.M-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 2 microU/ml), and plasma glucose decreased from 88 +/- 2 to 53 +/- 1 mg/dl for 12 h. In study 1, plasma glucose, glucose fluxes (D-[3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored. In study 2 (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretions (except for catecholamines) were prevented by somatostatin (0.5 mg/h iv) and metyrapone (0.5 g/4 h po), and glucagon, cortisol, and growth hormone were reinfused to reproduce the concentrations of study 1. In study 3 (lack of growth hormone increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma growth hormone 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 a growth hormone response caused a decrease in hepatic glucose production and an increase in glucose utilization that resulted in an approximately 25% greater hypoglycemia despite compensatory increases in plasma catecholamines. Plasma free fatty acid, 3-beta-hydroxybutyrate, and glycerol concentrations were reduced approximately 50%. It is concluded that growth hormone 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, Universita di Perugia, Italy.
Perriello
G
G
Torlone
E
E
Ventura
M M
MM
Santeusanio
F
F
Brunetti
P
P
Gerich
J E
JE
Bolli
G B
GB
D000328:Adult; D000409:Alanine / Q000097:blood; D002096:C-Peptide / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood / Q000494:pharmacology; D005990:Glycerol / Q000097:blood; D013006:Growth Hormone / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D012016:Reference Values; D013004:Somatostatin / Q000494:pharmacology
D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D013004:Somatostatin; D013006:Growth Hormone; D005934:Glucagon; D000409:Alanine; D005990:Glycerol; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine; D008797:Metyrapone