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 apoptoti...

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Bibliographic Details
Published in:Apoptosis (London) 2002-08, Vol.7 (4), p.335-345
Main Authors: Oyadomari, Seiichi, Araki, E, Mori, M
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - physiopathology
Endoplasmic Reticulum - pathology
Endoplasmic Reticulum - physiology
Islets of Langerhans - pathology
Islets of Langerhans - physiology
Mice
Molecular Chaperones - biosynthesis
Molecular Chaperones - genetics
Nitric Oxide - physiology
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Summary: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.
ISSN:1360-8185
DOI:10.1023/A:1016175429877