Fig. 3.

Trancriptional and poststrancriptional regulation of GLUT2 in mouse β-cells under normal and altered metabolic circumstances. a Overview of transcription factors with known regulatory function on Slc2a2 gene expression in mouse β-cells and their corresponding binding sites within the Slc2a2 promoter. In addition, factors that indirecrtly regulate Slc2a2 expression by altering the transcriptional activity of PDX1 are shown. b Summary of factors and pathways affecting GLUT2 regulation and function in a normal metabolic environment (green background) and under altered metabolic conditions (red background). According to a proposed model by Ohtsubo et al. [100, 101], high amounts of free fatty acids lead to the nuclear exclusion of the transcription factors FOXA2 and HNF1a, resulting in a decreased expression of Slc2a2 and Mgat4a, encoding the glycosyltransferase Gnt-4a. Consequently, N-glyocosylation of GLUT2 is impaired preventing the binding of lectin-receptors and the stabilization of GLUT2 at the cell surface. Non-glycosylated GLUT2 is increasingly found in endo- and lysosomes, resulting in a diminished glucose uptake and an impaired GSIS. Note that SREBP-1c acts as a transcriptional regulator in the nucleus and is only displayed in the cytosplasm for reasons of a clearer presentation