Pancreatic islet transplantation is a promising clinical treatment for type I diabetes (T1D), but success is limited by extensive beta cell death in the immediate post-transplant period, and impaired islet function in the longer term. Following transplantation, appropriate vascular remodelling is crucial to ensure the survival and function of engrafted islets. The sphingosine kinase pathway is an important regulator of vascular beds, but its role in the survival and function of transplanted islets is unknown. We observed that donor islets from mice deficient in SK1 (Sphk1-KO) contain a reduced number of resident intraislet vascular endothelial cells (ECs). Furthermore, we demonstrate that the main product of SK1, sphingosine-1-phosphate, controls the migration of intraislet ECs in vitro. We reveal in vivo that Sphk1-KO islets have an impaired ability to cure diabetes, compared to wildtype controls. Thus, SK1-deficient islets not only contain fewer resident vascular cells that participate in revascularisation, but likely also a reduced ability to recruit new vessels into the transplanted islet. Together, our data suggest that SK1 is important for islet revascularisation following transplantation and represents a novel clinical target for improving transplant outcomes.
- Received July 9, 2016.
- Accepted February 2, 2017.
- © 2017 by the American Diabetes Association.