Induction of α cell–restricted Gc in dedifferentiating β cells contributes to stress-induced β cell dysfunction
Year: 2019
Type: article
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 response than normal controls during hyperglycemic clamps. The data are consistent with a functional role of Gc activation in β cell dysfunction, and indicate that multiparity-induced diabetes is associated with altered β cell fate.
Source: JCI Insight
Institutions: Columbia University, University of Pennsylvania
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
OpenAlex ID: W2945901705