ChREBP mediates glucose-stimulated pancreatic β-cell proliferation.
ChREBP mediates glucose-stimulated pancreatic β-cell proliferation.
复制标题
作者：
Metukuri MR;Zhang P;Basantani MK;Chin C;Stamateris RE;Alonso LC;Takane KK;Gramignoli R;Strom SC;O'Doherty RM;Stewart AF;Vasavada RC;Garcia-Ocaña A;Scott DK
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.
登录
查看更多内容
影响因子：
7.7
作者：
Demozay D;Tsunekawa S;Briaud I;Shah R;Rhodes CJ
通讯作者：
Rhodes CJ
影响因子：
7.7
作者：
García-Ocaña, A;Vasavada, RC;Stewart, AF
通讯作者：
Stewart, AF
影响因子：
5.3
作者：
Assmann, Anke;Ueki, Kohjiro;Kulkarni, Rohit N.
通讯作者：
Kulkarni, Rohit N.
DOI：
10.1073/pnas.0401516101
发表时间：
2004-05-11
影响因子：
11.1
作者：
Iizuka, K;Bruick, RK;Uyeda, K
通讯作者：
Uyeda, K
影响因子：
7.7
作者：
Li, MV;Chang, B;Chan, L
通讯作者：
Chan, L