Harnessing the Endogenous Plasticity of Pancreatic Islets: A Feasible Regenerative Medicine Therapy for Diabetes?

ABSTRACT

Diabetes is a chronic metabolic disease caused by an absolute or relative deficiency in functional pancreatic ß-cells that leads to defective control of blood glucose. Current treatments for diabetes, despite their great beneficial effects on clinical symptoms, are not curative treatments, leading to a chronic dependence on insulin throughout life that does not prevent the secondary complications associated with diabetes. The overwhelming increase in DM incidence has led to a search for novel antidiabetic therapies aiming at the regeneration of the lost functional ß-cells to allow the re-establishment of the endogenous glucose homeostasis. Here we review several aspects that must be considered for the development of novel and successful regenerative therapies for diabetes first, the need to maintain the heterogeneity of islet ß-cells with several subpopulations of ß-cells characterized by different transcriptomic profiles correlating with differences in functionality and in resistance/behavior under stress conditions; second, the existence of an intrinsic islet plasticity that allows stimulus-mediated transcriptome alterations that trigger the transdifferentiation of islet non-ß-cells into ß-cells; and finally, the possibility of using agents that promote a fully functional/mature ß-cell phenotype to reduce and reverse the process of dedifferentiation of ß-cells during diabetes.