Premium
Reduced skeletal muscle secreted frizzled‐related protein 3 is associated with inflammation and insulin resistance
Author(s) -
Pachori Alok S.,
Madan Meenu,
Nunez Lopez Yury O.,
Yi Fanchao,
Meyer Christian,
Seyhan Attila A.
Publication year - 2017
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.21787
Subject(s) - endocrinology , medicine , insulin resistance , insulin , proinflammatory cytokine , inflammation , protein kinase b , biology , phosphorylation , microbiology and biotechnology
Objective To investigate the role of secreted frizzled‐related protein 3 (Sfrp3) in insulin sensitivity (ISi) and β‐cell function in humans across a spectrum of glucose homeostasis. Methods Subjects included those with normal glucose homeostasis (NGT; n = 18), prediabetes (PD; n = 11), or type 2 diabetes (T2D; n=12). Serum and skeletal muscle (SkM) Sfrp3 levels were measured by ELISA and qPCR, respectively, and insulin signaling pathway was assessed by Western blot. IS and β‐cell function were assessed by indices derived from frequently sampled intravenous glucose tolerance test. Results SkM Sfrp3 mRNA levels were significantly reduced in PD and T2D versus NGT. Similarly, serum Sfrp3 levels tended to be decreased in PD and T2D versus NGT. SkM Sfrp3 mRNA levels correlated negatively with circulating proinflammatory cytokines (IL‐6, IFN‐γ) and positively with IS. In vitro ‐differentiated myotubes from lean insulin‐sensitive subjects treated with either lipopolysaccharide (LPS) or recombinant IL‐6 demonstrated a dose‐dependent reduction in Sfrp3 gene expression. Treatment of myotubes with recombinant Sfrp3 restored LPS‐ and IL‐6‐induced attenuation of insulin‐stimulated Akt phosphorylation. Conclusions Inflammation‐induced reduction in SkM Sfrp3 expression may contribute to insulin resistance, and this effect may be prevented by addition of exogenous Sfrp3. Thus, Sfrp3 may be a novel target for insulin sensitization.