title: Endoplasmic reticulum stress and diabetes mellitus.
abstract: Pancreatic beta-cells are strongly engaged in protein secretion and have highly developed endoplasmic reticulum (ER). Proper folding of polypeptide into a three-dimensional structure is essential for cellular function and protein malfolding can threaten cell survival. Various conditions can perturb the protein folding in the ER, which is collectively called ER stress. In order to adapt ER stress conditions, the cells respond in three distinct ways such as transcriptional induction of ER chaperones, translational attenuation, and ER-associated degradation (ERAD). However, when ER functions are severely impaired, the cell is eliminated by apoptosis via transcriptional induction of CHOP/GADD153, the activation of cJUN NH2-terminal kinase, and/or the activation of caspase-12. Recent studies have revealed that beta-cell is one of the most susceptible cells for ER stress, and ER stress-mediated apoptosis in beta-cells can be a cause of diabetes. A comprehensive understanding of the impact of the ER stress pathway in beta-cells and how it relates to the development of diabetes may contribute to provide new targets for the prevention and treatment of this disease.
authors.affiliation: Department of Metabolic Medicine, Kumamoto University School of Medicine, Honjo Kumamoto 860-8556.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
authors.forename: Seiichi
authors.initials: S
authors.lastname: Oyadomari
authors.forename: Masataka
authors.initials: M
authors.lastname: Mori
mesh_terms: D000682:Amyloid / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D003920:Diabetes Mellitus / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000172:deficiency; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D017510:Protein Folding; D019892:eIF-2 Kinase / Q000172:deficiency
chemical_list: D000682:Amyloid; D015852:Eukaryotic Initiation Factor-2; D009569:Nitric Oxide; D019892:eIF-2 Kinase