Induction of α cell-restricted Gc in dedifferentiating β cells contributes to stress-induced β-cell dysfunction.

ABSTRACT: Diabetic β cell failure is associated with β cell dedifferentiation. To identify effector genes of dedifferentiation, we integrated analyses of histone methylation as a surrogate of gene activation status and RNA expression in β cells sorted from mice with multiparity-induced diabetes. Interestingly, only a narrow subset of genes demonstrated concordant changes to histone methylation and RNA levels in dedifferentiating β cells. Notable among them was the α cell signature gene Gc, encoding a vitamin D-binding protein. While diabetes was associated with Gc induction, Gc-deficient islets did not induce β cell dedifferentiation markers and maintained normal ex vivo insulin secretion in the face of metabolic challenge. Moreover, Gc-deficient mice exhibited a more robust insulin secretory respon

SUBMITTER: Kuo T 

PROVIDER: S-EPMC6629129 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature