Role of caspases in the regulation of apoptotic pancreatic islet beta-cells death.
The homeostatic control of beta-cell mass in normal and pathological conditions is based on the balance of proliferation, differentiation, and death of the insulin-secreting cells. A considerable body of evidence, accumulated during the last decade, has emphasized the significance of the disregulation of the mechanisms regulating the apoptosis of beta-cells in the sequence of events that lead to the development of diabetes. The identification of agents capable of interfering with this process needs to be based on a better understanding of the beta-cell specific pathways that are activated during apoptosis. The aim of this article is fivefold: (1) a review of the evidence for beta-cell apoptosis in Type I diabetes, Type II diabetes, and islet transplantation, (2) to review the common stimuli and their mechanisms in pancreatic beta-cell apoptosis, (3) to review the role of caspases and their activation pathway in beta-cell apoptosis, (4) to review the caspase cascade and morphological cellular changes in apoptotic beta-cells, and (5) to highlight the putative strategies for preventing pancreatic beta-cells from apoptosis.
Hui
Hongxiang
H
Division of Diabetes, Endocrinology and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Dotta
Francesco
F
Di Mario
Umberto
U
Perfetti
Riccardo
R
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000473:pathology / Q000503:physiopathology*; D004789:Enzyme Activation; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008954:Models, Biological; D010179:Pancreas / Q000166:cytology*
D020169:Caspases