Role of autophagy in diabetes and endoplasmic reticulum stress of pancreatic beta-cells.
10.3858/emm.2012.44.2.030
- Author:
Wenying QUAN
1
;
Yu Mi LIM
;
Myung Shik LEE
Author Information
1. Department of Medicine and Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 153-710, Korea. mslee0923@skku.edu
- Publication Type:Research Support, Non-U.S. Gov't ; Review
- Keywords:
autophagy;
diabetes mellitus;
endoplasmic reticulum stress;
insulin-secreting cells;
unfolded protein response
- MeSH:
Animals;
Autophagy/genetics/*physiology;
Diabetes Mellitus/genetics/*metabolism;
Endoplasmic Reticulum Stress/genetics/*physiology;
Humans;
Insulin-Secreting Cells/*metabolism
- From:Experimental & Molecular Medicine
2012;44(2):81-88
- CountryRepublic of Korea
- Language:English
-
Abstract:
Type 2 diabetes mellitus is characterized by insulin resistance and failure of pancreatic beta-cells producing insulin. Autophagy plays a crucial role in cellular homeostasis through degradation and recycling of organelles such as mitochondria or endoplasmic reticulum (ER). Here we discussed the role of beta-cell autophagy in development of diabetes, based on our own studies using mice with beta-cell-specific deletion of Atg7 (autophagy-related 7), an important autophagy gene, and studies by others. beta-cell-specific Atg7-null mice showed reduction in beta-cell mass and pancreatic insulin content. Insulin secretory function ex vivo was also impaired, which might be related to organelle dysfunction associated with autophagy deficiency. As a result, beta-cell-specific Atg7-null mice showed hypoinsulinemia and hyperglycemia. However, diabetes never developed in those mice. Obesity and/or lipid are physiological ER stresses that can precipitate beta-cell dysfunction. Our recent studies showed that beta-cell-specific Atg7-null mice, when bred with ob/ob mice, indeed become diabetic. Thus, autophagy deficiency in beta-cells could be a precipitating factor in the progression from obesity to diabetes due to inappropriate response to obesity-induced ER stress.
