Restoring insulin production for type 1 diabetes

Abstract

Current therapies for the treatment of type 1 diabetes include daily administration of exogenous insulin and, less frequently, whole-pancreas or islet transplantation. Insulin injections often result in inaccurate insulin doses, exposing the patient to hypo- and/or hyperglycemic episodes that lead to long-term complications. Islet transplantation is also limited by lack of high-quality islet donors, early graft failure, and chronic post-transplant immunosuppressive treatment. These barriers could be circumvented by designing a safe and efficient strategy to restore insulin production within the patient's body. Porcine islets have been considered as a possible alternative source of transplantable insulin-producing cells to replace human cadaveric islets. More recently, embryonic or induced pluripotent stem cells have also been examined for their ability to differentiate in vitro into pancreatic endocrine cells. Alternatively, it may be feasible to generate new β-cells by ectopic expression of key transcription factors in endogenous non-β-cells. Finally, engineering surrogate β-cells by in vivo delivery of the insulin gene to specific tissues is also being studied as a possible therapy for type 1 diabetes. In the present review, we discuss these different approaches to restore insulin production.