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Islet Specific Wnt Activation in Human Type II Diabetes

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 me...

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Autores principales: Lee, Seung-Hee, Demeterco, Carla, Geron, Ifat, Abrahamsson, Annelie, Levine, Fred, Itkin-Ansari, Pamela
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628766/
https://www.ncbi.nlm.nih.gov/pubmed/19165345
http://dx.doi.org/10.1155/2008/728763
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author Lee, Seung-Hee
Demeterco, Carla
Geron, Ifat
Abrahamsson, Annelie
Levine, Fred
Itkin-Ansari, Pamela
author_facet Lee, Seung-Hee
Demeterco, Carla
Geron, Ifat
Abrahamsson, Annelie
Levine, Fred
Itkin-Ansari, Pamela
author_sort Lee, Seung-Hee
collection PubMed
description 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, β-catenin, pGSK3β, 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 β-cell-directed diabetes therapy.
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spelling pubmed-26287662009-01-22 Islet Specific Wnt Activation in Human Type II Diabetes Lee, Seung-Hee Demeterco, Carla Geron, Ifat Abrahamsson, Annelie Levine, Fred Itkin-Ansari, Pamela Exp Diabetes Res Research Article 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, β-catenin, pGSK3β, 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 β-cell-directed diabetes therapy. Hindawi Publishing Corporation 2008 2009-01-20 /pmc/articles/PMC2628766/ /pubmed/19165345 http://dx.doi.org/10.1155/2008/728763 Text en Copyright © 2008 Seung-Hee Lee et al. https://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Research Article
Lee, Seung-Hee
Demeterco, Carla
Geron, Ifat
Abrahamsson, Annelie
Levine, Fred
Itkin-Ansari, Pamela
Islet Specific Wnt Activation in Human Type II Diabetes
title Islet Specific Wnt Activation in Human Type II Diabetes
title_full Islet Specific Wnt Activation in Human Type II Diabetes
title_fullStr Islet Specific Wnt Activation in Human Type II Diabetes
title_full_unstemmed Islet Specific Wnt Activation in Human Type II Diabetes
title_short Islet Specific Wnt Activation in Human Type II Diabetes
title_sort islet specific wnt activation in human type ii diabetes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628766/
https://www.ncbi.nlm.nih.gov/pubmed/19165345
http://dx.doi.org/10.1155/2008/728763
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