title: Insulin and endothelin in the acute regulation of adiponectin in vivo in humans.
abstract: OBJECTIVE
  In vitro, insulin and endothelin (ET) both modulate adiponectin secretion from adipocyte cell lines. The current studies were performed to assess whether endogenous ET contributes to the acute action of insulin infusions on adiponectin levels in vivo in humans.
  
  
  METHODS
  We studied 17 lean and 20 obese subjects (BMI 21.8 +/- 2.2 and 34.0 +/- 5.0 kg/m(2), respectively). Hyperinsulinemic euglycemic clamp studies were performed using insulin infusion rates of 10, 30, or 300 mU/m(2) per minute alone or with concurrent infusion of BQ123, an antagonist of type A ET receptors. Circulating adiponectin levels were assessed at baseline and after achievement of steady-state glucose with the insulin infusion.
  
  
  RESULTS
  Adiponectin levels were lower in obese than lean subjects (6.76 +/- 3.66 vs. 8.37 +/- 2.79 microg/mL, p = 0.0148 adjusted for differences across gender). Insulin infusions suppressed adiponectin by a mean of 7.8% (p < 0.0001). In a subset of 13 lean and 14 obese subjects for whom data with and without BQ123 were available, there was no evident effect of BQ123 to modulate clamp-associated suppression of adiponectin (p = 0.16). Surprisingly, there was no evident relationship between steady-state insulin concentrations and adiponectin suppression (r = 0.14, p = 0.30), and again no effect of BQ123 to modify this relationship was seen.
  
  
  CONCLUSIONS
  Despite baseline differences in adiponectin levels, we observed equal suppression of adiponectin with insulin infusions in lean and obese subjects. ET receptor antagonism with BQ123 did not modulate this effect, suggesting that endogenous ET does not have a role in modifying the acute effects of insulin on adiponectin production and/or disposition.
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Brame
authors.forename: Robert V
authors.initials: RV
authors.lastname: Considine
authors.forename: Mikako
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Alain D
authors.initials: AD
authors.lastname: Baron
authors.forename: Kieren J
authors.initials: KJ
authors.lastname: Mather
mesh_terms: D052242:Adiponectin; D000293:Adolescent; D000328:Adult; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood; D016232:Endothelins / Q000502:physiology*; D005260:Female; D015309:Glucose Clamp Technique; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D010456:Peptides, Cyclic / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)