Carbon monoxide protects pancreatic β-cells from apoptosis and improves islet function/survival after transplantation
Carbon monoxide protects pancreatic β-cells from apoptosis and improves islet function/survival after transplantation
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DOI：
10.2337/diabetes.51.4.994
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发表时间：
2002-04-01
期刊：
影响因子：
7.7
通讯作者：
Tobiasch, E
中科院分区：
文献类型：
--
作者：
Günther, L;Berberat, PO;Tobiasch, E
胰岛移植治疗自身免疫性1型糖尿病通常不能发挥功能（原发性无功能），可能是因为胰岛β细胞凋亡。我们表明，一氧化碳（CO）（血红素加氧酶活性的产物）可以保护β细胞免受细胞凋亡。保护作用是通过鸟苷酸环化酶活化、环GMP（cGMP）的产生和cGMP依赖性蛋白激酶的活化介导的。当β细胞在凋亡刺激之前暴露于CO 1小时时，仍然观察到这种抗凋亡作用。以类似的方式，小鼠胰岛暴露于CO仅2小时的功能显着优于移植后的胰岛没有暴露于CO。这些研究结果表明，CO在改善胰岛功能/生存移植后在人类的潜在治疗应用。
Pancreatic islets transplanted to treat autoimmune type 1 diabetes often fail to function (primary nonfunction), likely because of islet beta-cell apoptosis. We show that carbon monoxide (CO), a product of heme oxygenase activity, protects beta-cells from apoptosis. Protection is mediated through guanylate cyclase activation, generation of cyclic GMP (cGMP), and activation of cGMP-dependent protein kinases. This antiapoptotic effect is still observed when beta-cells are exposed to CO for 1 h before the apoptotic stimulus. In a similar manner, mouse islets exposed to CO for just 2 h function significantly better after transplantation than islets not exposed to CO. These findings suggest a potential therapeutic application for CO in improving islet function/survival after transplantation in humans.