Section of Cell Biology, Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, Faculty of Medicine, Imperial College London, UK.
Biochem Biophys Res Commun. 2010 Nov 12;402(2):252-7. doi: 10.1016/j.bbrc.2010.10.010. Epub 2010 Oct 8.
Carbohydrate responsive element-binding protein (ChREBP) is a transcription factor whose expression and activity are increased in pancreatic β-cells maintained at elevated glucose concentrations. We show here that ChREBP inactivation in clonal pancreatic MIN6 β-cells results in an increase in Pdx-1 expression at low glucose and to a small, but significant, increase in Ins2, GcK and MafA gene expression at high glucose concentrations. Conversely, adenovirus-mediated over-expression of ChREBP in mouse pancreatic islets results in decreases in Pdx-1, MafA, Ins1, Ins2 and GcK mRNA levels. These data suggest that strategies to reduce ChREBP activity might protect against β-cell dysfunction in type 2 diabetes.
碳水化合物反应元件结合蛋白（ChREBP）是一种转录因子，其在维持高葡萄糖浓度的胰岛β细胞中的表达和活性增加。我们在这里显示，在克隆的胰岛 MIN6 β细胞中 ChREBP 的失活导致在低糖条件下 Pdx-1 的表达增加，并且在高葡萄糖浓度下 Ins2、GcK 和 MafA 基因的表达略有但显著增加。相反，腺病毒介导的 ChREBP 在小鼠胰岛中的过表达导致 Pdx-1、MafA、Ins1、Ins2 和 GcK mRNA 水平降低。这些数据表明，降低 ChREBP 活性的策略可能有助于预防 2 型糖尿病中的β细胞功能障碍。
