title: Acute hyperinsulinemia differentially regulates interstitial and circulating adiponectin oligomeric pattern in lean and insulin-resistant, obese individuals.
abstract: BACKGROUND
  Hyperinsulinemia emerges as a negative modulator of the circulating high-molecular-weight adiponectin multimers.
  
  
  OBJECTIVE
  Here we asked whether, in vivo, acute hyperinsulinemia regulates adiponectin formation and oligomeric complex distribution at the transcriptional or posttranslational level.
  
  
  METHODS
  Nine lean and nine uncomplicated obese males were studied in the postabsorptive state and during a euglycemic-hyperinsulinemic clamp combined with the microdialysis technique. Subcutaneous abdominal adipose tissue biopsies and interstitial and serum samples were taken at baseline and after the hyperinsulinemia. Adiponectin complexes were characterized by nonheating/nonreducing SDS-PAGE.
  
  
  RESULTS
  At baseline, serum and interstitial total adiponectin levels were lower (P < 0.01) in obese than in lean subjects primarily due to a reduction of the high-molecular-weight isoforms. After hyperinsulinemia, serum and interstitial total adiponectin was reduced in both groups. The degree of adiponectin reduction was more prominent in interstitial fluid than in serum. Lean individuals showed an equal suppression of the high-, low-, and middle-molecular-weight adiponectin complexes both in serum and in situ (P < 0.01 vs. basal). In obese subjects, despite the lower interstitial adiponectin subfractions, insulin challenge reduced significantly the circulating middle-molecular-weight forms only. At the mRNA level, adiponectin and its receptors 1 and 2, as well as the abundance of the endoplasmic reticulum chaperone proteins ERp44 and Epsilonro1-Lalpha were similar within the groups, before and after the clamp.
  
  
  CONCLUSIONS
  In human obesity, the impaired adiponectin oligomeric pattern in the circulation is mimicked at the tissue level, and hyperinsulinemia may differentially affect the compartmental distribution of the adiponectin complexes.
authors.affiliation: Department of Molecular and Clinical Medicine, The Lundberg Laboratory for Diabetes Research, The Sahlgrenska Academy at Göteborg University, Center of Excellence for Cardiovascular and Metabolic Research, SE-413 45 Göteborg, Sweden. gmurdolo@tiscalinet.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Murdolo
authors.forename: Ann
authors.initials: A
authors.lastname: Hammarstedt
authors.forename: Martin
authors.initials: M
authors.lastname: Schmelz
authors.forename: Per-Anders
authors.initials: PA
authors.lastname: Jansson
authors.forename: Ulf
authors.initials: U
authors.lastname: Smith
mesh_terms: D000208:Acute Disease; D017667:Adipocytes / Q000166:cytology / Q000473:pathology; D052242:Adiponectin / Q000097:blood / Q000378:metabolism*; D000328:Adult; D015992:Body Mass Index; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007408:Intestinal Absorption; D008970:Molecular Weight; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D013739:Testosterone / Q000097:blood; D013851:Thinness / Q000097:blood / Q000378:metabolism*; D055105:Waist Circumference; D049629:Waist-Hip Ratio
chemical_list: D052242:Adiponectin; D013739:Testosterone