SLC2A2 gene is upregulated in diabetes and dowregulated in insulin treatment: participation of HNFs (1α, 3β and 4α)

Abstract

ObjectiveInvestigate the role of HNFs (1á, 3â, 4á) at SLC2A2 (GLUT2 gene) in liver of diabetic and insulin treated diabetic rats.Methods3 month old Wistar rats, allocated into non diabetic (C), diabetic (D), diabetic treated with saline (DS) or insulin (DI) for 1, 4 and 6 days (d). The mRNA of GLUT2 and HNFs was analyzed by RT‐PCR. The HNFs binding activity into SLC2A2 promoter was analyzed by EMSA.ResultsIn comparison to C, D rats showed: hyperglycemia, polyuria, glycosuria without ketonuria, less gain of weight; increase of: I) GLUT2 (P<0,0001), HNF1á (P<0,05), HNF3â (P<0,01) and HNF4á (P<0,05) mRNA expression, II) bindig activity of HNF1á (P<0,05), HNF3â (P<0,01) and HNF4á (P<0,05) into SLC2A2. In comparison to DS, DI rats showed: reduction of glycemia, increased of body weight; decrease of: I) mRNA expression: GLUT2 after 4 and 6d (P< 0,001), HNF1á after 6d (P<0,05), HNF3â after 4 and 6d (P<0,001) and HNF4á after 6d (P<0,05), II) binding activity into SLC2A2: HNF1á after 4 and 6d (P<0,01), HNF3â after 1, 4 (P<0,05) and 6d (P<0,01) and HNF4á after 6d (P<0,05).ConclusionThe SLC2A2 overexpression is related to expression and activity of HNFs (1á, 3â, 4á). Furthermore, insulin therapy‐induced regulation of SLC2A2 expression also involves HNFs. Considering the importance of the GLUT2, we hope that the knowledge of the SLC2A2 transcriptional regulation may contribute to control gene expression.FAPESP 2009/03871‐7