title: Role of autophagy in diabetes and endoplasmic reticulum stress of pancreatic β-cells.
abstract: Type 2 diabetes mellitus is characterized by insulin resistance and failure of pancreatic β-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 β-cell autophagy in development of diabetes, based on our own studies using mice with β-cell-specific deletion of Atg7 (autophagy-related 7 ), an important autophagy gene, and studies by others. β-cell-specific Atg7-null mice showed reduction in β-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, β-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 β-cell dysfunction. Our recent studies showed that β-cellspecific Atg7-null mice, when bred with ob/ob mice, indeed become diabetic. Thus, autophagy deficiency in β-cells could be a precipitating factor in the progression from obesity to diabetes due to inappropriate response to obesity-induced ER stress.
authors.affiliation: Department of Medicine and Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 153-710, Korea.
authors.forename: Wenying
authors.initials: W
authors.lastname: Quan
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Lim
authors.forename: Myung Shik
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*