PT  - JOURNAL ARTICLE
AU  - Metukuri, Mallikarjuna R.
AU  - Zhang, Pili
AU  - Basantani, Mahesh K.
AU  - Chin, Connie
AU  - Stamateris, Rachel E.
AU  - Alonso, Laura C.
AU  - Takane, Karen K.
AU  - Gramignoli, Roberto
AU  - Strom, Stephen C.
AU  - O’Doherty, Robert M.
AU  - Stewart, Andrew F.
AU  - Vasavada, Rupangi C.
AU  - Garcia-Ocaña, Adolfo
AU  - Scott, Donald K.
TI  - ChREBP Mediates Glucose-Stimulated Pancreatic β-Cell Proliferation
AID  - 10.2337/db11-0802
DP  - 2012 Aug 01
TA  - Diabetes
PG  - 2004--2015
VI  - 61
IP  - 8
4099  - http://diabetes.diabetesjournals.org/content/61/8/2004.short
4100  - http://diabetes.diabetesjournals.org/content/61/8/2004.full
SO  - Diabetes2012 Aug 01; 61
AB  - Glucose stimulates rodent and human β-cell replication, but the intracellular signaling mechanisms are poorly understood. Carbohydrate response element-binding protein (ChREBP) is a lipogenic glucose-sensing transcription factor with unknown functions in pancreatic β-cells. We tested the hypothesis that ChREBP is required for glucose-stimulated β-cell proliferation. The relative expression of ChREBP was determined in liver and β-cells using quantitative RT-PCR (qRT-PCR), immunoblotting, and immunohistochemistry. Loss- and gain-of-function studies were performed using small interfering RNA and genetic deletion of ChREBP and adenoviral overexpression of ChREBP in rodent and human β-cells. Proliferation was measured by 5-bromo-2′-deoxyuridine incorporation, [3H]thymidine incorporation, and fluorescence-activated cell sorter analysis. In addition, the expression of cell cycle regulatory genes was measured by qRT-PCR and immunoblotting. ChREBP expression was comparable with liver in mouse pancreata and in rat and human islets. Depletion of ChREBP decreased glucose-stimulated proliferation in β-cells isolated from ChREBP−/− mice, in INS-1–derived 832/13 cells, and in primary rat and human β-cells. Furthermore, depletion of ChREBP decreased the glucose-stimulated expression of cell cycle accelerators. Overexpression of ChREBP amplified glucose-stimulated proliferation in rat and human β-cells, with concomitant increases in cyclin gene expression. In conclusion, ChREBP mediates glucose-stimulated proliferation in pancreatic β-cells.