Endoplasmic reticulum stress-mediated apoptosis in pancreatic beta-cells.
Apoptotic cell death in pancreatic beta-cells is involved in the pathogenesis of diabetes. Signals from death receptors and DNA damage have been widely accepted as being triggers of apoptosis in beta-cells. Recent studies indicated that the endoplasmic reticulum (ER) can sense and transduce apoptotic signals. Various genetic and environmental stresses interfere with protein folding in the ER and induce ER stress. In mammals, ER stress transducer proteins IRE1, PERK and ATF6 activate both survival and apoptotic pathways. The former includes transcriptional induction of ER chaperones, translational attenuation, and ER-associated degradation (ERAD) while the latter includes transcriptional induction of CHOP/GADD153, the activation of cJUN NH(2)-terminal kinase, and the activation of caspase-12. A characteristic feature of beta-cells is the highly developed ER apparently due to a heavy engagement in insulin secretion. beta-cells are most susceptible to ER stress. The recent studies reviewed in this article revealed that ER stress-mediated apoptosis in beta-cells plays an important role in the development of diabetes.
Oyadomari
Seiichi
S
Department of Molecular Genetics, Kumamoto University School of Medicine, Honjo 2-2-1, Kumamoto 860-0811, Japan. oya@gpo.kumamoto-u.ac.jp
Araki
E
E
Mori
M
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D004721:Endoplasmic Reticulum / Q000473:pathology / Q000502:physiology*; D007515:Islets of Langerhans / Q000473:pathology / Q000502:physiology*; D051379:Mice; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics; D009569:Nitric Oxide / Q000502:physiology
D018832:Molecular Chaperones; D009569:Nitric Oxide