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Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells
Insulin secretion from pancreatic β-cells is impaired in all forms of diabetes. The resultant hyperglycaemia has deleterious effects on many tissues, including β-cells. Here we show that chronic hyperglycaemia impairs glucose metabolism and alters expression of metabolic genes in pancreatic islets....
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123088/ https://www.ncbi.nlm.nih.gov/pubmed/27882918 http://dx.doi.org/10.1038/ncomms13496 |
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author | Brereton, Melissa F. Rohm, Maria Shimomura, Kenju Holland, Christian Tornovsky-Babeay, Sharona Dadon, Daniela Iberl, Michaela Chibalina, Margarita V. Lee, Sheena Glaser, Benjamin Dor, Yuval Rorsman, Patrik Clark, Anne Ashcroft, Frances M. |
author_facet | Brereton, Melissa F. Rohm, Maria Shimomura, Kenju Holland, Christian Tornovsky-Babeay, Sharona Dadon, Daniela Iberl, Michaela Chibalina, Margarita V. Lee, Sheena Glaser, Benjamin Dor, Yuval Rorsman, Patrik Clark, Anne Ashcroft, Frances M. |
author_sort | Brereton, Melissa F. |
collection | PubMed |
description | Insulin secretion from pancreatic β-cells is impaired in all forms of diabetes. The resultant hyperglycaemia has deleterious effects on many tissues, including β-cells. Here we show that chronic hyperglycaemia impairs glucose metabolism and alters expression of metabolic genes in pancreatic islets. In a mouse model of human neonatal diabetes, hyperglycaemia results in marked glycogen accumulation, and increased apoptosis in β-cells. Sulphonylurea therapy rapidly normalizes blood glucose levels, dissipates glycogen stores, increases autophagy and restores β-cell metabolism. Insulin therapy has the same effect but with slower kinetics. Similar changes are observed in mice expressing an activating glucokinase mutation, in in vitro models of hyperglycaemia, and in islets from type-2 diabetic patients. Altered β-cell metabolism may underlie both the progressive impairment of insulin secretion and reduced β-cell mass in diabetes. |
format | Online Article Text |
id | pubmed-5123088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51230882016-11-29 Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells Brereton, Melissa F. Rohm, Maria Shimomura, Kenju Holland, Christian Tornovsky-Babeay, Sharona Dadon, Daniela Iberl, Michaela Chibalina, Margarita V. Lee, Sheena Glaser, Benjamin Dor, Yuval Rorsman, Patrik Clark, Anne Ashcroft, Frances M. Nat Commun Article Insulin secretion from pancreatic β-cells is impaired in all forms of diabetes. The resultant hyperglycaemia has deleterious effects on many tissues, including β-cells. Here we show that chronic hyperglycaemia impairs glucose metabolism and alters expression of metabolic genes in pancreatic islets. In a mouse model of human neonatal diabetes, hyperglycaemia results in marked glycogen accumulation, and increased apoptosis in β-cells. Sulphonylurea therapy rapidly normalizes blood glucose levels, dissipates glycogen stores, increases autophagy and restores β-cell metabolism. Insulin therapy has the same effect but with slower kinetics. Similar changes are observed in mice expressing an activating glucokinase mutation, in in vitro models of hyperglycaemia, and in islets from type-2 diabetic patients. Altered β-cell metabolism may underlie both the progressive impairment of insulin secretion and reduced β-cell mass in diabetes. Nature Publishing Group 2016-11-24 /pmc/articles/PMC5123088/ /pubmed/27882918 http://dx.doi.org/10.1038/ncomms13496 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 Brereton, Melissa F. Rohm, Maria Shimomura, Kenju Holland, Christian Tornovsky-Babeay, Sharona Dadon, Daniela Iberl, Michaela Chibalina, Margarita V. Lee, Sheena Glaser, Benjamin Dor, Yuval Rorsman, Patrik Clark, Anne Ashcroft, Frances M. Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells |
title | Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells |
title_full | Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells |
title_fullStr | Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells |
title_full_unstemmed | Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells |
title_short | Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells |
title_sort | hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123088/ https://www.ncbi.nlm.nih.gov/pubmed/27882918 http://dx.doi.org/10.1038/ncomms13496 |
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