title: Estrogen blunts neuroendocrine and metabolic responses to hypoglycemia.
abstract: This study tested the hypothesis that estrogen is the mechanism responsible for the sexual dimorphism present in the neuroendocrine and metabolic responses to hypoglycemia. Postmenopausal women receiving (E2; n = 8) or not receiving (NO E2; n = 9) estrogen replacement were compared with age- and BMI-matched male subjects (n = 8) during a single-step 2-h hyperinsulinemic-hypoglycemic clamp. Plasma insulin (599 +/- 28 pmol/l) and glucose (2.9 +/- 0.03 mmol/l) levels were similar among all groups during the glucose clamp. In response to hypoglycemia, epinephrine (2.8 +/- 0.6 vs. 5.8 +/- 0.8 and 4.4 +/- 0.5 nmol/l), glucagon (57 +/- 8 vs. 77 +/- 8 and 126 +/- 18 ng/l), and endogenous glucose production (2 +/- 2 vs. 10 +/- 2 and 6 +/- 3 micro mol x kg(-1) x min(-1)) were significantly lower in E2 vs. both NO E2 and male subjects (P < 0.05). These reduced counterregulatory responses resulted in significantly greater glucose infusion rates (16 +/- 2 vs. 6 +/- 2 and 6 +/- 3 micro mol x kg(-1) x min(-1); P < 0.01) in E2 vs. both NO E2 and male subjects. Pancreatic polypeptide was significantly lower (P < 0.05) in both the E2 and NO E2 groups compared with the male subjects (136 +/- 20 and 136 +/- 23 vs. 194 +/- 16 pmol/l). Last, glycerol (36 +/- 3 vs. 47 +/- 5 micro mol/l; P < 0.05), lactate (1.4 +/- 0.1 vs. 1.8 +/- 0.2 mmol/l; P < 0.05), and muscle sympathetic nerve activity (19 +/- 4 to 27 +/- 4 vs. 27 +/- 5 to 42 +/- 6 bursts/min; P < 0.05) responses to hypoglycemia were all significantly lower in E2 vs. NO E2 subjects. We conclude that estrogen appears to play a major role in the sexual dimorphism present in counterregulatory responses to hypoglycemia in healthy humans.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine and Nashville Veterans Affairs Medical Center, Nashville, Tennessee, USA. darleen.sandoval@vanderbilt.edu
authors.forename: Darleen A
authors.initials: DA
authors.lastname: Sandoval
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Ertl
authors.forename: M Antoinette
authors.initials: MA
authors.lastname: Richardson
authors.forename: Donna B
authors.initials: DB
authors.lastname: Tate
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Davis
mesh_terms: D004837:Epinephrine / Q000097:blood*; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood*; D005943:Gluconeogenesis; D015309:Glucose Clamp Technique; D006706:Homeostasis; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006946:Hyperinsulinism; D007003:Hypoglycemia / Q000097:blood*; D007328:Insulin / Q000097:blood*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019382:Human Growth Hormone; D004958:Estradiol; D005934:Glucagon; D006854:Hydrocortisone; D004837:Epinephrine