An alternative spliced variant of circulating soluble tumor necrosis factor-alpha receptor-2 is paradoxically associated with insulin action

European Journal of Endocrinology
José Manuel Fernández-RealWifredo Ricart

Abstract

Serum concentrations of soluble tumor necrosis factor-alpha (TNF-alpha) receptor 2 (sTNFR2) are associated with insulin resistance. In a recent study, we provided evidence for the existence of a biologically active form of sTNFR2 produced by alternative splicing (DS-TNFR2). We aimed to evaluate whether this circulating DS-TNFR2 is associated with insulin action in humans. Real time PCR (light cycler technology) evaluated DS-TNFR2 expression in monocytes. DS-TNFR2 was measured using a monoclonal antibody against an epitope present in TNFR2 (first 14 residues of the juxtamembrane region) but predicted to be absent in soluble proteolytic cleavage-produced TNFR2. Insulin sensitivity was measured using euglycemic hyperinsulinemic clamp (n = 76) and homeostatic model of assessment (HOMA) value in a replication study of 223 subjects. Real time PCR confirmed gene expression of DS-TNFR2 in monocytes from healthy subjects. A significant and positive association was found between serum DS-TNFR2 concentration and insulin sensitivity (P = 0.032, n = 76). This association was most significant in subjects with normal glucose tolerance (r = 0.44, P = 0.002). The subjects in whom DS-TNFR2 was detectable were more insulin sensitive than those wi...Continue Reading

Citations

Aug 23, 2012·Gene·Olga KelemenStefan Stamm
Feb 6, 2007·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Eduardo EsteveJose-Manuel Fernández-Real
Jan 5, 2013·Cell Cycle·Cécile Jacovetti, Romano Regazzi
May 26, 2010·International Journal of Obesity : Journal of the International Association for the Study of Obesity·D GniuliG Mingrone
Oct 18, 2007·Current Opinion in Endocrinology, Diabetes, and Obesity

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