SLC2A2 gene expression in kidney of diabetic rats is regulated by HNF-1alpha and HNF-3beta.
We hypothesize that, in kidney of diabetic rats, hepatocyte nuclear factors (HNF-1alpha and HNF-3beta) play a critical role in the overexpression of solute carrier 2A2 (SLC2A2) gene. Diabetic rats submitted or not to rapid (up to 12h) 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-1alpha and HNF-3beta expression and binding activity. Additional 2-fold increase in GLUT2 mRNA and HNF-3beta expression/activity was observed in 12-h insulin-treated rats. Six-day insulin treatment decreased GLUT2 mRNA and HNF-1alpha expression and activity to levels of non-diabetic rats, whereas HNF-3beta 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-1alpha and HNF-3beta in kidney of diabetic rats. Furthermore, recovery of SLC2A2 gene after 6-day insulin treatment also involves HNF-1alpha and HNF-3beta activity.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes 1524, 05505-900 Sao Paulo (SP), Brazil. ubiratan@icb.usp.br
H S
HS
Freitas
B D
BD
Schaan
A
A
David-Silva
R
R
Sabino-Silva
M M
MM
Okamoto
A B
AB
Alves-Wagner
R C
RC
Mori
U F
UF
Machado
D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000502:physiology*; D051542:Hepatocyte Nuclear Factor 3-beta / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D051273:Glucose Transporter Type 2; D051538:Hepatocyte Nuclear Factor 1-alpha; D007328:Insulin; D012333:RNA, Messenger; C495683:Slc2a2 protein, rat; D051542:Hepatocyte Nuclear Factor 3-beta