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.