title: Analysis of insulin sensitivity in adipose tissue of patients with primary aldosteronism.
abstract: OBJECTIVE
  The objective of the study was to assess the effect of high aldosterone levels on insulin sensitivity of adipose tissue in humans.
  
  
  METHODS
  Visceral adipose tissue (VAT) was obtained from patients with aldosterone-producing adenoma (APA; n=14) and, as controls, nonfunctioning adenoma (NFA; n=14) undergoing laparoscopic adrenalectomy. Homeostasis model assessment index was higher and potassium was lower in APA than NFA (P<0.05). Immunohistochemistry, Western blotting, and real-time PCR were used to detect and quantify mineralocorticoid receptor (MR) expression. Transcript levels of peroxisome proliferative-activated receptor-gamma, insulin receptor, glucose transporter 4, insulin receptor substrate-1 and -2, leptin, adiponectin, IL-6, monocyte chemoattractant protein-1, glucocorticoid receptor (GR)-alpha, 11beta-hydroxysteroid dehydrogenase (HSD11B) type 1, and HSD11B2 were quantified. The effect of increasing aldosterone concentrations on 2-deoxy-[3H]d-glucose uptake was tested in human sc abdominal adipocytes.
  
  
  RESULTS
  Expression of MR was demonstrated in VAT, with no difference between APA and NFA as to mRNA levels of MR, GRalpha, HSD11B1, and glucose metabolism and inflammation factors. In cultured adipocytes, basal and insulin-stimulated glucose uptake were unaffected by 1-100 nM (normal/hyperaldosteronism) and impaired only by much higher, up to 10 microM, aldosterone concentrations. The impairment was prevented by RU486 but not by eplerenone.
  
  
  CONCLUSIONS
  Gene expression of insulin signaling/inflammatory molecules was similar in VAT of APA and NFA patients, not supporting an effect of aldosterone excess on insulin sensitivity of adipose tissues. Only at pharmacological concentrations and through GR activation, aldosterone reduced glucose uptake in adipocytes. Insulin resistance in primary aldosteronism might occur in compartments other than fat and/or depend on concurrent environmental factors.
authors.affiliation: Department of Medical and Surgical Sciences, University of Padova, Via Ospedale 105, 35128 Padova, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Urbanet
authors.forename: Catia
authors.initials: C
authors.lastname: Pilon
authors.forename: Alessandra
authors.initials: A
authors.lastname: Calcagno
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peschechera
authors.forename: Edwige-Ludiwyne
authors.initials: EL
authors.lastname: Hubert
authors.forename: Gilberta
authors.initials: G
authors.lastname: Giacchetti
authors.forename: Celso
authors.initials: C
authors.lastname: Gomez-Sanchez
authors.forename: Paolo
authors.initials: P
authors.lastname: Mulatero
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Toffanin
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Sonino
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Zennaro
authors.forename: Francesco
authors.initials: F
authors.lastname: Giorgino
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
authors.forename: Francesco
authors.initials: F
authors.lastname: Fallo
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism; D018246:Adrenocortical Adenoma / Q000235:genetics / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D015153:Blotting, Western; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006929:Hyperaldosteronism / Q000378:metabolism*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D052242:Adiponectin; D007328:Insulin; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012083:Renin; D006854:Hydrocortisone