Bibliographic Details
| Title: |
ChREBP binding to fatty acid synthase and L-type pyruvate kinase genes is stimulated by glucose in pancreatic β-cells |
| Authors: |
Gabriela da Silva Xavier, Guy A. Rutter, Frédérique Diraison, Chrysovalantis Andreolas, Isabelle Leclerc |
| Source: |
Journal of Lipid Research, Vol 47, Iss 11, Pp 2482-2491 (2006) |
| Publisher Information: |
Elsevier, 2006. |
| Publication Year: |
2006 |
| Collection: |
LCC:Biochemistry |
| Subject Terms: |
glucolipotoxicity, lipogenic genes, chromatin immunoprecipitation, Biochemistry, QD415-436 |
| More Details: |
Pancreatic β-cell dysfunction is central to the pathogenesis of type 2 diabetes and may involve secretory failure through glucolipotoxity. The relative importance of the transcription factors carbohydrate-responsive element binding protein (ChREBP), sterol-responsive element binding protein-1c (SREBP-1c), and upstream stimulatory factor (USF) in the induction of lipogenic genes by glucose remains unclear. By confocal imaging, we show that ChREBP translocates to the nucleus in MIN6 β cells in response to glucose. Both ChREBP and SREBP-1c were required for the induction of the fatty acid synthase (FAS) promoter by glucose, and chromatin immunoprecipitation (ChIP) assay revealed that glucose induced the binding of both ChREBP and SREBP-1c to the FAS promoter without affecting USF2 binding. By contrast, ChIP assay revealed that high glucose prompted direct binding of ChREBP, but not SREBP-1c or USF2, to the liver-type pyruvate kinase (L-PK) promoter. This event was indispensable for the induction of the L-PK gene by glucose, as demonstrated by RNA silencing, single-cell promoter analysis, and quantitative real-time PCR. We conclude that ChREBP is a critical regulator of lipogenic genes in the β cell and may play a role in the development of glucolipotoxicity and β cell failure through alteration of gene expression in type 2 diabetes. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
0022-2275 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S002222752043384X; https://doaj.org/toc/0022-2275 |
| DOI: |
10.1194/jlr.M600289-JLR200 |
| Access URL: |
https://doaj.org/article/4d29dd48fdd54b4b84eb5ea0adc87db4 |
| Accession Number: |
edsdoj.4d29dd48fdd54b4b84eb5ea0adc87db4 |
| Database: |
Directory of Open Access Journals |
