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Acute hyperinsulinemia differentially regulates interstitial and circulating adiponectin oligomeric pattern in lean and insulin-resistant, obese individuals

Journal article
Authors Giuseppe Murdolo
Ann Hammarstedt
M. Schmelz
Per-Anders Jansson
Ulf Smith
Published in J Clin Endocrinol Metab
Volume 94
Issue 11
Pages 4508-16
ISSN 1945-7197 (Electronic)
Publication year 2009
Published at Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 4508-16
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Medical and Health Sciences

Abstract

CONTEXT: Hyperinsulinemia emerges as a negative modulator of the circulating high-molecular-weight adiponectin multimers. OBJECTIVES: Here we asked whether, in vivo, acute hyperinsulinemia regulates adiponectin formation and oligomeric complex distribution at the transcriptional or posttranslational level. DESIGN: 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.

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