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Role of autophagy in beta-cell function and mass

Cited 38 time in Web of Science Cited 42 time in Scopus
Authors
Hur, K. Y.; Jung, H. S.; Lee, M. -S.
Issue Date
2010-10
Publisher
WILEY-BLACKWELL
Citation
DIABETES OBESITY & METABOLISM; Vol.12 ; 20-26
Keywords
autophagyER stresscell death
Abstract
Type 2 diabetes (T2D) is characterized by decreased insulin secretion and action. Decreased insulin secretion results from a reduction in pancreatic beta-cell mass and/or function. Apoptosis, oxidative stress, mitochondrial dysfunction and endoplasmic reticulum (ER) stress responses including JNK activation have been suggested as mechanisms for the changes of pancreatic beta-cells in T2D; however, the underlying causes were not clearly elucidated. Autophagy is an intracellular process that plays crucial roles in cellular homeostasis through degradation and recycling of organelles. We have reported increased apoptosis and decreased proliferation of beta-cells with resultant reduction in the beta-cell mass in beta-cell-specific autophagy-deficient mice. Morphological analysis of beta-cells revealed accumulation of ubiquitinated proteins, swollen mitochondria and distended ER. Insulin secretory function ex vivo was also impaired. As a result, beta-cell-specific autophagy-deficient mice showed hypoinsulinaemia and hyperglycaemia. These results suggested that autophagy is necessary to maintain the structure, mass and function of pancreatic beta-cells. In addition, as autophagy may play a protective role against ER stress and rejuvenates organelle function, impaired autophagy may lead to mitochondrial dysfunction and ER stress, which have been implicated as potential causes of insulin resistance. Therefore, in addition to beta-cell homeostasis, dysregulated autophagy may possibly be involved in diverse aspects of the pathogenesis of diabetes.
ISSN
1462-8902
Language
English
URI
https://hdl.handle.net/10371/77589
DOI
https://doi.org/10.1111/j.1463-1326.2010.01278.x
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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