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Adipose- and muscle-derived Wnts trigger pancreatic β-cell adaptation to systemic insulin resistance

Wnt signaling molecules are associated with obesity, hyperlipidemia, and type 2 diabetes (T2D). Here, we show that two Wnt proteins, WNT3a and WNT4, are specifically secreted by skeletal muscle and adipose tissue during the development of insulin resistance and play an important role in cross-talk b...

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Autores principales: Kozinski, Kamil, Jazurek, Magdalena, Dobrzyn, Pawel, Janikiewicz, Justyna, Kolczynska, Katarzyna, Gajda, Anna, Dobrzyn, Agnieszka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985739/
https://www.ncbi.nlm.nih.gov/pubmed/27527335
http://dx.doi.org/10.1038/srep31553
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author Kozinski, Kamil
Jazurek, Magdalena
Dobrzyn, Pawel
Janikiewicz, Justyna
Kolczynska, Katarzyna
Gajda, Anna
Dobrzyn, Agnieszka
author_facet Kozinski, Kamil
Jazurek, Magdalena
Dobrzyn, Pawel
Janikiewicz, Justyna
Kolczynska, Katarzyna
Gajda, Anna
Dobrzyn, Agnieszka
author_sort Kozinski, Kamil
collection PubMed
description Wnt signaling molecules are associated with obesity, hyperlipidemia, and type 2 diabetes (T2D). Here, we show that two Wnt proteins, WNT3a and WNT4, are specifically secreted by skeletal muscle and adipose tissue during the development of insulin resistance and play an important role in cross-talk between insulin-resistant tissues and pancreatic beta cells. The activation of Frizzled receptor and Wnt signaling in pancreatic islets via circulating WNT3a in blood resulted in higher insulin secretion and an increase in beta cell proliferation, thus leading to islet adaptation in a pre-diabetic state. Interestingly, in fully developed T2D, the expression profiles of Wnt3a and Wnt4 in adipose tissue and muscle cells and blood plasma levels of these proteins were opposite to the pre-diabetic state, thus favoring the downregulation of Wnt signaling in beta cells and resulting in dysfunctional pancreatic islets. These results demonstrate that alterations in the secretion profile of a canonical Wnt activator (WNT3a) and inhibitor (WNT4) from insulin-resistant tissues during the development of T2D are responsible for triggering progression from a pre-diabetic to a diabetic state. We also show here that WNT3a and WNT4 are potent myokines, and their expression and secretion are regulated in response to nutritional and metabolic changes.
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spelling pubmed-49857392016-08-22 Adipose- and muscle-derived Wnts trigger pancreatic β-cell adaptation to systemic insulin resistance Kozinski, Kamil Jazurek, Magdalena Dobrzyn, Pawel Janikiewicz, Justyna Kolczynska, Katarzyna Gajda, Anna Dobrzyn, Agnieszka Sci Rep Article Wnt signaling molecules are associated with obesity, hyperlipidemia, and type 2 diabetes (T2D). Here, we show that two Wnt proteins, WNT3a and WNT4, are specifically secreted by skeletal muscle and adipose tissue during the development of insulin resistance and play an important role in cross-talk between insulin-resistant tissues and pancreatic beta cells. The activation of Frizzled receptor and Wnt signaling in pancreatic islets via circulating WNT3a in blood resulted in higher insulin secretion and an increase in beta cell proliferation, thus leading to islet adaptation in a pre-diabetic state. Interestingly, in fully developed T2D, the expression profiles of Wnt3a and Wnt4 in adipose tissue and muscle cells and blood plasma levels of these proteins were opposite to the pre-diabetic state, thus favoring the downregulation of Wnt signaling in beta cells and resulting in dysfunctional pancreatic islets. These results demonstrate that alterations in the secretion profile of a canonical Wnt activator (WNT3a) and inhibitor (WNT4) from insulin-resistant tissues during the development of T2D are responsible for triggering progression from a pre-diabetic to a diabetic state. We also show here that WNT3a and WNT4 are potent myokines, and their expression and secretion are regulated in response to nutritional and metabolic changes. Nature Publishing Group 2016-08-16 /pmc/articles/PMC4985739/ /pubmed/27527335 http://dx.doi.org/10.1038/srep31553 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Kozinski, Kamil
Jazurek, Magdalena
Dobrzyn, Pawel
Janikiewicz, Justyna
Kolczynska, Katarzyna
Gajda, Anna
Dobrzyn, Agnieszka
Adipose- and muscle-derived Wnts trigger pancreatic β-cell adaptation to systemic insulin resistance
title Adipose- and muscle-derived Wnts trigger pancreatic β-cell adaptation to systemic insulin resistance
title_full Adipose- and muscle-derived Wnts trigger pancreatic β-cell adaptation to systemic insulin resistance
title_fullStr Adipose- and muscle-derived Wnts trigger pancreatic β-cell adaptation to systemic insulin resistance
title_full_unstemmed Adipose- and muscle-derived Wnts trigger pancreatic β-cell adaptation to systemic insulin resistance
title_short Adipose- and muscle-derived Wnts trigger pancreatic β-cell adaptation to systemic insulin resistance
title_sort adipose- and muscle-derived wnts trigger pancreatic β-cell adaptation to systemic insulin resistance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985739/
https://www.ncbi.nlm.nih.gov/pubmed/27527335
http://dx.doi.org/10.1038/srep31553
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