Chronic hyperglycaemia is detrimental to pancreatic β-cells by causing impaired insulin secretion and diminished β-cell function through glucotoxicity. Understanding the mechanisms underlying β-cell survival is crucial for the prevention of β-cell failure associated with glucotoxicity. Autophagy is a dynamic lysosomal degradation process that protects organisms against metabolic stress. To date, little is known about the physiological function of autophagy in the pathogenesis of diabetes. In the present study, we explored the roles of autophagy in the survival of pancreatic β-cells exposed to high glucose using pharmacological and genetic manipulation of autophagy. We demonstrated that chronic high glucose increases autophagy in rat INS-1 (832/13) cells and pancreatic islets, and that this increase is enhanced by inhibition of 5′-AMP-activated protein kinase. Our results also indicate that stimulation of autophagy rescues pancreatic β-cells from high-glucose-induced cell death and inhibition of autophagy augments caspase-3 activation, suggesting that autophagy plays a protective role in the survival of pancreatic β-cells. Greater knowledge of the molecular mechanisms linking autophagy and β-cell survival may unveil novel therapeutic targets needed to preserve β-cell function.
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February 2010
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Research Article|
January 15 2010
Activation of autophagy through modulation of 5′-AMP-activated protein kinase protects pancreatic β-cells from high glucose Available to Purchase
Diana Han;
Diana Han
*Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, U.S.A.
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Byungho Yang;
Byungho Yang
*Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, U.S.A.
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L. Karl Olson;
L. Karl Olson
†Department of Physiology, Michigan State University, East Lansing, MI 48824, U.S.A.
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Alexander Greenstein;
Alexander Greenstein
*Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, U.S.A.
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Seung-Hoon Baek;
Seung-Hoon Baek
‡Department of Neurology and Ophthalmology, Michigan State University, East Lansing, MI 48824, U.S.A.
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Kate J. Claycombe;
Kate J. Claycombe
*Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, U.S.A.
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John L. Goudreau;
John L. Goudreau
‡Department of Neurology and Ophthalmology, Michigan State University, East Lansing, MI 48824, U.S.A.
§Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, U.S.A.
∥Neuroscience Program, Michigan State University, East Lansing, MI 48824, U.S.A.
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Seong-Woon Yu;
Seong-Woon Yu
‡Department of Neurology and Ophthalmology, Michigan State University, East Lansing, MI 48824, U.S.A.
§Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, U.S.A.
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Eun-Kyoung Kim
Eun-Kyoung Kim
1
*Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, U.S.A.
‡Department of Neurology and Ophthalmology, Michigan State University, East Lansing, MI 48824, U.S.A.
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
March 31 2009
Revision Received:
October 13 2009
Accepted:
November 11 2009
Accepted Manuscript online:
November 11 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 425 (3): 541–551.
Article history
Received:
March 31 2009
Revision Received:
October 13 2009
Accepted:
November 11 2009
Accepted Manuscript online:
November 11 2009
Citation
Diana Han, Byungho Yang, L. Karl Olson, Alexander Greenstein, Seung-Hoon Baek, Kate J. Claycombe, John L. Goudreau, Seong-Woon Yu, Eun-Kyoung Kim; Activation of autophagy through modulation of 5′-AMP-activated protein kinase protects pancreatic β-cells from high glucose. Biochem J 1 February 2010; 425 (3): 541–551. doi: https://doi.org/10.1042/BJ20090429
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