Carbon Monoxide Protects Pancreatic -Cells From Apoptosis and Improves Islet Function/Survival After

Pancreatic islets transplanted to treat autoimmune type 1 diabetes often fail to function (primary nonfunction), likely because of islet -cell apoptosis. We show that carbon monoxide (CO), a product of heme oxygenase activity, protects -cells from apoptosis. Protection is mediated through guanylate cyclase activation, genera-tion of cyclic GMP (cGMP), and activation of cGMP-dependent protein kinases. This antiapoptotic effect is still observed when -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 signif-icantly better after transplantation than islets not ex-posed to CO. These findings suggest a potential therapeutic application for CO in improving islet func-tion/survival after transplantation in humans. Diabete