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Intracellular pathways of pancreatic β‐cell apoptosis in type 1 diabetes
Author(s) -
Thomas Helen E.,
Kay Thomas W.
Publication year - 2011
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1253
Subject(s) - granzyme b , apoptosis , intracellular , perforin , islet , pancreatic islets , programmed cell death , microbiology and biotechnology , type 2 diabetes , granzyme , type 1 diabetes , chemistry , diabetes mellitus , biology , cancer research , endocrinology , biochemistry , cytotoxic t cell , in vitro
Background Apoptosis of β cells is a feature of type 1 diabetes. It is also increasingly recognized in type 2 diabetes and islet graft rejection. Methods We have studied the intracellular pathways that regulate β‐cell apoptosis in type 1 and 2 diabetes. We have examined the role of Bid, a pro‐apoptotic member of the Bcl‐2 family, using islets from mice deficient in Bid. We also studied the Bcl‐2 family molecules involved in killing by using high concentrations of reducing sugars such as glucose or ribose. Results We found that Bid‐deficient islets are protected from recombinant human perforin and granzyme B, as well as from Fas‐mediated killing. This makes Bid a target for protection of β cells from multiple insults relevant to type 1 diabetes. In contrast to granzyme B and death receptor signalling, we found that islets lacking Bim or Puma were protected from glucose toxicity. Conclusions Our data indicate that different stimuli activate different initiator molecules in the Bcl‐2‐regulated pathway in β cells. Copyright © 2011 John Wiley & Sons, Ltd.