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Macroautophagy in homeostasis of pancreatic β-cell

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Authors
Jung, Hye Seung; Lee, Myung-Shik
Issue Date
2009-02-16
Publisher
LANDES BIOSCIENCE
Citation
AUTOPHAGY; Vol.5 2; 241-243
Keywords
autophagymitochondriaendoplasmic reticulumdiabetespancreatic beta-cell
Abstract
Diabetes mellitus is characterized by decreased insulin secretion and action. Decreased insulin secretion results from a reduction in pancreatic beta-cell mass and function. Apoptosis, oxidative stress, mitochondrial dysfunction, and ER stress responses including JNK activation have been suggested as mechanisms of the changes of pancreatic beta-cells in type 2 diabetes, however, the underlying causes were not clearly elucidated. Autophagy is an intracellular process that plays a crucial role in cellular homeostasis through degradation and recycling of organelles constitutively or in response to the environmental condition. We studied the role of autophagy in pancreatic beta-cells using mice with beta-cell-specific deletion of the Atg7 (autophagy-related 7) gene. Atg7-mutant mice showed increased apoptosis and decreased proliferation of beta-cells with resultant reduction in beta-cell mass. Pancreatic insulin content was decreased due to the decreased beta-cell mass and reduced number of insulin granules. Morphological analysis of beta-cells revealed accumulation of ubiquitinated proteins, swollen mitochondria, and distended ER. Insulin secretary function ex vivo was also impaired. As a result, autophagy-deficient mice showed hypoinsulinemia and hyperglycemia. These results suggest that autophagy is necessary to maintain structure, mass and function of pancreatic beta-cells. Here we discuss the significance of autophagy in pancreatic beta-cells with its potential relevance to the development of diabetes.
ISSN
1554-8627
Language
English
URI
http://hdl.handle.net/10371/77406
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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