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Publication : Inhibition of secreted frizzled-related protein 5 improves glucose metabolism.

First Author  Rulifson IC Year  2014
Journal  Am J Physiol Endocrinol Metab Volume  307
Issue  12 Pages  E1144-52
PubMed ID  25370851 Mgi Jnum  J:218529
Mgi Id  MGI:5617883 Doi  10.1152/ajpendo.00283.2014
Citation  Rulifson IC, et al. (2014) Inhibition of secreted frizzled-related protein 5 improves glucose metabolism. Am J Physiol Endocrinol Metab 307(12):E1144-52
abstractText  Elucidating the role of secreted frizzled-related protein 5 (SFRP5) in metabolism and obesity has been complicated by contradictory findings when knockout mice were used to determine metabolic phenotypes. By overexpressing SFRP5 in obese, prediabetic mice we consistently observed elevated hyperglycemia and glucose intolerance, supporting SFRP5 as a negative regulator of glucose metabolism. Accordingly, Sfrp5 mRNA expression analysis of both epididymal and subcutaneous adipose depots of mice indicated a correlation with obesity. Thus, we generated a monoclonal antibody (mAb) against SFRP5 to ascertain the effect of SFRP5 inhibition in vivo. Congruent with SFRP5 overexpression worsening blood glucose levels and glucose intolerance, anti-SFRP5 mAb therapy improved these phenotypes in vivo. The results from both the overexpression and mAb inhibition studies suggest a role for SFRP5 in glucose metabolism and pancreatic beta-cell function and thus establish the use of an anti-SFRP5 mAb as a potential approach to treat type 2 diabetes.
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