title: Stimulation of both type I and type II corticosteroid receptors blunts counterregulatory responses to subsequent hypoglycemia in healthy man.
abstract: 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.
authors.affiliation: Department of Medicine, Div. of Diabetes, Endocrinology, and Metabolism,Vanderbilt University Medical Center 7465 MRB IV, Nashville, TN 37232-0475, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Gustavson
authors.forename: Darleen A
authors.initials: DA
authors.lastname: Sandoval
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Ertl
authors.forename: Shichun
authors.initials: S
authors.lastname: Bao
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Davis
mesh_terms: 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*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D003907:Dexamethasone; D005438:Fludrocortisone