Analysis of Insulin Sensitivity in Adipose Tissue of Patients with Primary Aldosteronism

作者：Urbanet Riccardo; Pilon Catia; Calcagno Alessandra; Peschechera Alessandro; Hubert Edwige Ludiwyne; Giacchetti Gilberta; Gomez Sanchez Celso; Mulatero Paolo; Toffanin Mariacristina; Sonino Nicoletta; Zennaro Maria Christina; Giorgino Francesco; Vettor Roberto; Fallo Francesco^*

来源：Journal of Clinical Endocrinology & Metabolism, 2010, 95(8): 4037-4042.

DOI：10.1210/jc.2010-0097

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, 11 beta-hydroxysteroid dehydrogenase (HSD11B) type 1, and HSD11B2 were quantified. The effect of increasing aldosterone concentrations on 2-deoxy-[(3)H]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, GR alpha, 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 mu M, 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. (J Clin Endocrinol Metab 95: 4037-4042, 2010)

• 出版日期2010-8