Stimulation of both type I and type II corticosteroid receptors blunts counterregulatory responses to subsequent hypoglycemia in healthy man.
Antecedent increases of corticosteroids can blunt counterregulatory responses to subsequent stress. Our aim was to determine whether prior activation of type I corticosteroid (mineralocorticoid) or type II corticosteroid (glucocorticoid) receptors blunts counterregulatory responses to subsequent hypoglycemia. Healthy volunteers participated in five randomized 2-day protocols. Day 1 involved morning and afternoon 2-h hyperinsulinemic (9 pmol.kg(-1).min(-1)) euglycemic clamps (PE; n = 14), hypoglycemic clamps (PH; n = 14), or euglycemic clamps with oral fludrocortisone (PE + F; type I agonist, 0.2 mg, n = 14), oral dexamethasone (PE + D; type II agonist, 0.75 mg, n = 13), or both (PE + F + D; n = 14). Day 2 was identical in all protocols and consisted of a 2-h hyperinsulinemic hypoglycemic clamp. Day 2 insulin (625 +/- 40 pmol/l) and glucose (2.9 +/- 0.1 mmol/l) levels were similar among groups. Levels of epinephrine, norepinephrine, glucagon, growth hormone, and MSNA were significantly blunted by prior activation of both type I and type II corticosteroid receptors to PE. Prior activation of both corticosteroid receptors also significantly blunted NEFA during subsequent hypoglycemia. Thus, levels of a wide spectrum of key counterregulatory mechanisms (neuroendocrine, ANS, and metabolic) were blunted by antecedent pharmacological stimulation of either type I or type II corticosteroid receptors in healthy man. These data suggest that activation of type I corticosteroid receptors in man can have acute and profound regulating effects on physiological stress in man. Both type I and type II corticosteroid receptors may be involved in the multiple mechanisms controlling counterregulatory responses to hypoglycemia in healthy man.
Gustavson
Stephanie M
SM
Department of Medicine, Div. of Diabetes, Endocrinology, and Metabolism,Vanderbilt University Medical Center 7465 MRB IV, Nashville, TN 37232-0475, USA.
Sandoval
Darleen A
DA
Ertl
Andrew C
AC
Bao
Shichun
S
Raj
Satish R
SR
Davis
Stephen N
SN
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003907:Dexamethasone / Q000008:administration & dosage; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005438:Fludrocortisone / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D006946:Hyperinsulinism; D007003:Hypoglycemia / Q000503:physiopathology*; D008297:Male; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000187:drug effects / Q000502:physiology*; D018161:Receptors, Mineralocorticoid / Q000819:agonists / Q000187:drug effects / Q000502:physiology*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D003907:Dexamethasone; D005438:Fludrocortisone