title: Hyperinsulinemia causes activation of the hypothalamus-pituitary-adrenal axis in humans.
abstract: OBJECTIVE
  Hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis is frequently found in hyperinsulinemic subjects, such as patients with diabetes or abdominal obesity. Here, the question has been posed as to whether hyperinsulinemia increases HPA secretory activity.
  
  
  METHODS
  We performed paired-euglycemic and stepwise hypoglycemic (76-66-56-46 mg/dl)-clamp experiments in two groups (each of 15 healthy men) at different insulin infusions rates, ie, 1.5 mU/min/kg (low-insulin condition) and 15.0 mU/min/kg (high-insulin condition).
  
  
  RESULTS
  During the euglycemic clamp, the high rate insulin infusion increased plasma ACTH levels, whereas plasma ACTH levels remained essentially unchanged during the low-insulin condition (condition by time interaction, P=0.008). Likewise, serum cortisol levels were higher during the high- vs low-insulin condition (condition by time interaction, P=0.004). During the hypoglycemic clamp, plasma ACTH levels did not differ between the low- vs high-insulin condition, while serum cortisol levels were higher during the high- vs low-insulin condition at the beginning of the clamp (plasma glucose approximately 76 mg/dl; P=0.032).
  
  
  CONCLUSIONS
  Data indicate that hyperinsulinemia acutely increases HPA secretory activity in healthy men. This finding appears to be relevant to the pathogenesis of many clinical abnormalities associated which diabetes and abdominal adiposity, often referred to as the metabolic syndrome.
authors.affiliation: Department of Internal Medicine I, Medical University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany. fruehwal@kfg.mu-luebeck.de
authors.forename: B
authors.initials: B
authors.lastname: Fruehwald-Schultes
authors.forename: W
authors.initials: W
authors.lastname: Kern
authors.forename: J
authors.initials: J
authors.lastname: Born
authors.forename: H L
authors.initials: HL
authors.lastname: Fehm
authors.forename: A
authors.initials: A
authors.lastname: Peters
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D015309:Glucose Clamp Technique; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006946:Hyperinsulinism; D007003:Hypoglycemia; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007328:Insulin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone