Journal article
Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells
- Abstract:
- 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 use a mouse model of human neonatal diabetes to show that chronic hyperglycemia impairs glucose metabolism and alters expression of metabolic genes in pancreatic islets. This 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 diabetes patients. Altered β-cell metabolism may underlie both the progressive impairment of insulin secretion and reduced β-cell mass in diabetes.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 8.3MB, Terms of use)
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- Publisher copy:
- 10.1038/ncomms13496
Authors
+ Royal Society
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- Funding agency for:
- Ashcroft, F
- Grant:
- Research Wolfson Merit Award
+ University of Oxford
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- Funding agency for:
- Rohm, M
- Grant:
- postdoctoral fellowship
+ European Research Council
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- Funding agency for:
- Ashcroft, F
- Grant:
- Research Wolfson Merit Award
- Advanced grant 322620
+ Wellcome Trust
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- Funding agency for:
- Brereton, M
- Grant:
- OXION Training Fellowship
- 884655, 089795
- Publisher:
- Nature Publishing Group
- Journal:
- Nature Communications More from this journal
- Volume:
- 7
- Article number:
- 13496
- Publication date:
- 2016-11-24
- Acceptance date:
- 2016-10-07
- DOI:
- ISSN:
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2041-1723
- Keywords:
- Pubs id:
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pubs:648543
- UUID:
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uuid:44f29080-48ef-42d9-a457-80bbd134cb77
- Local pid:
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pubs:648543
- Deposit date:
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2016-10-10
- ARK identifier:
Terms of use
- Copyright holder:
- Brereton et al
- Copyright date:
- 2016
- Notes:
- © 2016 The Authors. 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/
- Licence:
- CC Attribution (CC BY)
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