St Vincent's Institute of Medical Research, Department of Medicine, University of Melbourne, St Vincent's Hospital, Fitzroy, Melbourne, Victoria, Australia.
Diabetes Metab Res Rev. 2011 Nov;27(8):790-6. doi: 10.1002/dmrr.1253.
Apoptosis of β cells is a feature of type 1 diabetes. It is also increasingly recognized in type 2 diabetes and islet graft rejection.
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.
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.
Our data indicate that different stimuli activate different initiator molecules in the Bcl-2-regulated pathway in β cells.
β 细胞的凋亡是 1 型糖尿病的一个特征。在 2 型糖尿病和胰岛移植物排斥中也越来越多地被认识到。
我们研究了调节 1 型和 2 型糖尿病中β细胞凋亡的细胞内途径。我们使用 Bid 缺陷的小鼠胰岛研究了促凋亡 Bcl-2 家族成员 Bid 的作用。我们还使用高浓度的还原糖（如葡萄糖或核糖）研究了参与杀伤的 Bcl-2 家族分子。
我们发现 Bid 缺陷的胰岛免受重组人穿孔素和颗粒酶 B 以及 Fas 介导的杀伤的影响。这使得 Bid 成为保护β细胞免受与 1 型糖尿病相关的多种损伤的靶标。与颗粒酶 B 和死亡受体信号传导相反，我们发现缺乏 Bim 或 Puma 的胰岛对葡萄糖毒性具有保护作用。
我们的数据表明，不同的刺激物在β细胞中 Bcl-2 调节途径中激活不同的起始分子。
