Diabetes and Obesity Research Laboratory, Sackler Faculty of Medicine, Felsenstein Medical Research Center, Rabin Medical Center, Tel-Aviv University, Beilinson Campus, 49100, Petah Tikva, Israel.
Histochem Cell Biol. 2012 Jun;137(6):801-10. doi: 10.1007/s00418-012-0925-4. Epub 2012 Feb 5.
Insulin-producing beta cells are known to be highly susceptible to hypoxia, which is a major factor in their destruction after pancreatic islet transplantation. However, whether the glucagon-producing pancreatic islet alpha cells are sensitive to hypoxia is not known. Our objective was to compare the sensitivity of alpha and beta cells to hypoxia. Isolated rat pancreatic islets were exposed to hypoxia (1% oxygen, 94% N(2), 5% CO(2)) for 3 days. The viability of the alpha and beta cells, as well as the stimulus-specific secretion of glucagon and insulin, was evaluated. A quantitative analysis of the proportion of beta to alpha cells indicated that, under normoxic conditions, islet cells were composed mainly of beta cells (87 ± 3%) with only 13 ± 3% alpha cells. Instead, hypoxia treatment significantly increased the proportion of alpha cells (40 ± 13%) and decreased the proportion of beta cells to 60 ± 13%. Using the fluorescent TUNEL assay we found that only a few percent of beta cells and alpha cells were apoptotic in normoxia. In contrast, hypoxia induced an abundance of apoptotic beta cells (61 ± 22%) and had no effect on the level of apoptosis in alpha cells. In conclusion, this study demonstrates that hypoxia results in severe functional abnormality in both beta and alpha cells while alpha cells display significantly decreased rate of apoptosis compared to intensive apoptotic injury of beta cells. These findings have implications for the understanding of the possible role of hypoxia in the pathophysiology of diabetes.
胰岛β细胞对缺氧非常敏感，这是胰岛移植后β细胞破坏的主要因素。然而，产生胰高血糖素的胰岛α细胞是否对缺氧敏感尚不清楚。我们的目的是比较α细胞和β细胞对缺氧的敏感性。将分离的大鼠胰岛暴露于缺氧（1%氧气、94%氮气、5%二氧化碳）中 3 天。评估α和β细胞的活力以及胰高血糖素和胰岛素的刺激特异性分泌。β细胞与α细胞比例的定量分析表明，在正常氧条件下，胰岛细胞主要由β细胞（87±3%）组成，仅有 13±3%的α细胞。相反，缺氧处理显著增加了α细胞的比例（40±13%），而β细胞的比例下降到 60±13%。使用荧光 TUNEL 测定法，我们发现正常氧条件下只有少数β细胞和α细胞发生凋亡。相比之下，缺氧诱导大量β细胞凋亡（61±22%），对α细胞的凋亡水平没有影响。总之，本研究表明，缺氧导致β细胞和α细胞均出现严重的功能异常，而与β细胞的大量凋亡损伤相比，α细胞的凋亡率显著降低。这些发现对理解缺氧在糖尿病发病机制中的可能作用具有重要意义。
