FTY720 preserved islet β-cell mass by inhibiting apoptosis and increasing survival of β-cells in db/db mice

Background FTY720, an analogue of sphingosine-1-phosphate, has shown potential in the treatment of several autoimmune diseases, such as multiple sclerosis, type 1 diabetes and systemic lupus erythematosus. It prevents development or cure of autoimmune diabetes in animal models. Recently, we reported that FTY720 also prevents development of diabetes in db/db mice by beta-cell regeneration in vivo. This study investigated the effect of FTY720 on apoptosis in beta-cells in db/db mice treated with FTY720 16 weeks. Methods Six week old female db/db mice were divided into control and FTY720 groups. FTY720 (10 mg/kg) was orally administrated daily. Body weights and fasting glucose levels were measured once a week after overnight fasting. After 16 weeks of treatment, oral glucose and insulin tolerance tests were performed, serum insulin levels and insulin contents in pancreas were determined, and then all mice were subjected to physiological and histological analyses. Results FTY720-treated mice showed normal fasting glucose levels, improved glucose tolerance with normal insulin sensitivity and restored beta-cell function to produce and secret insulin. Pancreas histology revealed that FTY720 prevented islet damage and preserved beta-cell mass by inhibiting apoptosis and increasing beta-cell survival in pancreatic islets. Conclusions We concluded that early intervention with FTY720 in db/db mice can prevent development of diabetes through preserving beta-cell mass by inhibiting apoptosis and increasing survival of islet beta-cells. Copyright (C) 2012 John Wiley & Sons, Ltd.