| First Author | Kuo T | Year | 2019 |
| Journal | JCI Insight | Volume | 5 |
| PubMed ID | 31120862 | Mgi Jnum | J:278289 |
| Mgi Id | MGI:6342380 | Doi | 10.1172/jci.insight.128351 |
| Citation | Kuo T, et al. (2019) Induction of alpha cell-restricted Gc in dedifferentiating beta cells contributes to stress-induced beta-cell dysfunction. JCI Insight 5 |
| abstractText | Diabetic beta cell failure is associated with beta 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 beta 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 beta cells. Notable among them was the alpha cell signature gene Gc, encoding a vitamin D-binding protein. While diabetes was associated with Gc induction, Gc-deficient islets did not induce beta 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 beta cell dysfunction, and indicate that multiparity-induced diabetes is associated with altered beta cell fate. |
