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Inhibition of secreted frizzled-related protein 5 improves glucose metabolism.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2014 Dec 15; Vol. 307 (12), pp. E1144-52. Date of Electronic Publication: 2014 Nov 04. - Publication Year :
- 2014
-
Abstract
- 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 β-cell function and thus establish the use of an anti-SFRP5 mAb as a potential approach to treat type 2 diabetes.<br /> (Copyright © 2014 the American Physiological Society.)
- Subjects :
- Adaptor Proteins, Signal Transducing
Animals
Antibodies, Monoclonal immunology
Diabetes Mellitus, Type 2 genetics
Diabetes Mellitus, Type 2 metabolism
Immunoglobulin G immunology
Insulin-Secreting Cells drug effects
Intercellular Signaling Peptides and Proteins genetics
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Obesity complications
Obesity genetics
Obesity metabolism
Glucose metabolism
Insulin-Secreting Cells metabolism
Intercellular Signaling Peptides and Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1555
- Volume :
- 307
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 25370851
- Full Text :
- https://doi.org/10.1152/ajpendo.00283.2014