title: Intracellular pathways of pancreatic β-cell apoptosis in type 1 diabetes.
abstract: 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.
authors: St Vincent's Institute of Medical Research, Department of Medicine, University of Melbourne, St Vincent's Hospital, Fitzroy, Melbourne, Victoria, Australia. hthomas@svi.edu.au
authors: Helen E
authors: HE
authors: Thomas
authors: Thomas W
authors: TW
authors: Kay
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D051023:BH3 Interacting Domain Death Agonist Protein / Q000172:deficiency / Q000502:physiology; D000072224:Bcl-2-Like Protein 11; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D053804:Granzymes / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C000606775:BCL2L11 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D053418:Death Domain Receptor Signaling Adaptor Proteins; D008565:Membrane Proteins; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D054353:Perforin; D053804:Granzymes