SLC2A2 gene expression in kidney of diabetic rats is regulated by HNF-1α and HNF-3β

We hypothesize that, in kidney of diabetic rats, hepatocyte nuclear factors (HNF-1α and HNF-3β) play a critical role in the overexpression of solute carrier 2A2 (SLC2A2) gene. Diabetic rats submitted or not to rapid (up to 12 h) and short-term (1, 4 and 6 days) insulin treatment were investigated. Twofold increase in GLUT2 mRNA was observed in diabetic, accompanied by significant increases in HNF-1α and HNF-3β expression and binding activity. Additional 2-fold increase in GLUT2 mRNA and HNF-3β expression/activity was observed in 12-h insulin-treated rats. Six-day insulin treatment decreased GLUT2 mRNA and HNF-1α expression and activity to levels of non-diabetic rats, whereas HNF-3β decreased to levels of non-insulin-treated diabetic rats. Our results provide evidence for a link between the overexpression of SLC2A2 gene and the transcriptional activity of HNF-1α and HNF-3β in kidney of diabetic rats. Furthermore, recovery of SLC2A2 gene after 6-day insulin treatment also involves HNF-1α and HNF-3β activity.