| First Author | Zhang P | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 12 | Pages | 4158-70 |
| PubMed ID | 26384380 | Mgi Jnum | J:246403 |
| Mgi Id | MGI:5924853 | Doi | 10.2337/db15-0239 |
| Citation | Zhang P, et al. (2015) Induction of the ChREBPbeta Isoform Is Essential for Glucose-Stimulated beta-Cell Proliferation. Diabetes 64(12):4158-70 |
| abstractText | Carbohydrate-responsive element-binding protein (ChREBP) is a glucose-sensing transcription factor required for glucose-stimulated proliferation of pancreatic beta-cells in rodents and humans. The full-length isoform (ChREBPalpha) has a low glucose inhibitory domain (LID) that restrains the transactivation domain when glucose catabolism is minimal. A novel isoform of ChREBP (ChREBPbeta) was recently described that lacks the LID domain and is therefore constitutively and more potently active. ChREBPbeta has not been described in beta-cells nor has its role in glucose-stimulated proliferation been determined. We found that ChREBPbeta is highly expressed in response to glucose, particularly with prolonged culture in hyperglycemic conditions. In addition, small interfering RNAs that knocked down ChREBPbeta transcripts without affecting ChREBPalpha expression or activity decreased glucose-stimulated expression of carbohydrate response element-containing genes and glucose-stimulated proliferation in INS-1 cells and in isolated rat islets. Quantitative chromatin immunoprecipitation, electrophoretic mobility shift assays, and luciferase reporter assays were used to demonstrate that ChREBP binds to a newly identified powerful carbohydrate response element in beta-cells and hepatocytes, distinct from that in differentiated 3T3-L1 adipocytes. We conclude that ChREBPbeta contributes to glucose-stimulated gene expression and proliferation in beta-cells, with recruitment of ChREBPalpha to tissue-specific elements of the ChREBPbeta isoform promoter. |
