Background: The arrangement of beta cells within islets of Langerhans produces a gain-of-function in insulin release through the generation of rhythmic activity patterns. A privileged role for individual beta cells in orchestrating these responses has long-been suspected, but not directly examined.
Objective and hypotheses: Identify and characterize a rare subpopulation of beta cells tasked with pacemaking insulin release.
Method: Optogenetics, photopharmacology and photopainting approaches were used to functionally interrogate and label single beta cells in situ within islets.
Results: Specialized cells, termed hubs, possess lowered expression of beta cell identity markers (Pdx1, Nkx6.1, insulin etc) and are metabolically adapted, as evidenced by increased expression of glucokinase and elevated mitochondrial potential. Importantly, hubs are specifically targeted by proinflammatory and glucotoxic insults to induce widespread islet dysfunction.
Conclusion: The islet is wired by hubs, whose failure may contribute to type 1 and type 2 diabetes. Importantly, the finding that the beta cell population is heterogeneous has clear repercussions for the de novo construction of islets from stem cells, as well as treatment of diabetes.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology