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Experimental Diabetes Research
Volume 2008, Article ID 728763, 13 pages
http://dx.doi.org/10.1155/2008/728763
Research Article

Islet Specific Wnt Activation in Human Type II Diabetes

1Development and Aging Program, Burnham Institute for Medical Research, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA
2Department of Pediatrics, University of California San Diego, 9500 Gilman Dr, MC 0816, La Jolla, CA 92093, USA
3Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
4Sanford Children's Health Research Center, Burnham Institute for Medical Research, 10901 N. Torrey Pines Road, CA 92037, USA

Received 3 June 2008; Accepted 7 October 2008

Academic Editor: Anjan Kowluru

Copyright © 2008 Seung-Hee Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The Wnt pathway effector gene TCF7L2 has been linked to type II diabetes, making it important to study the role of Wnt signaling in diabetes pathogenesis. We examined the expression of multiple Wnt pathway components in pancreases from normal individuals and type II diabetic individuals. Multiple members of the Wnt signaling pathway, including TCF7L2, Wnt2b, -catenin, pGSK3 , TCF3, cyclinD1, and c-myc, were undetectable or expressed at low levels in islets from nondiabetic individuals, but were also upregulated specifically in islets of type II diabetic patients. Culture of pancreatic tissue and islet isolation led to Wnt activation that was reversed by the Wnt antagonist sFRP, demonstrating that Wnt activation in that setting was due to soluble Wnt factors. These data support a model in which the Wnt pathway plays a dynamic role in the pathogenesis of type II diabetes and suggest manipulation of Wnt signaling as a new approach to -cell-directed diabetes therapy.