Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Nephron Physiol 2007;105:p42–p51 DOI: 10.1159/000098442 Insulin but Not Phlorizin Treatment Induces a Transient Increase in GLUT2 Gene Expression in the Kidney of Diabetic Rats Helayne Soares Freitas a Beatriz D’Agord Schaan b Robinson Sabino da Silva a Maristela Mitiko Okamoto a Maria Oliveira-Souza a Ubiratan Fabres Machado a a Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, and b Experimental Medicine Department, Institute of Cardiology of the State of Rio Grande do Sul/University Foundation of Cardiology, Porto Alegre, Rio Grande do Sul, Brazil mia, with opposite effects upon plasma insulin and urinary glucose, and both treatments decreased GLUT2 mRNA and protein (p ! 0.05). Conclusion: In kidney of diabetic rats, an initial and transient upregulation of GLUT2 was induced spe- cifically by insulin only. The 6-day normalization of GLUT2, however, was induced by both insulin and phlorizin treat- ment, which seems to be related to the plasma glucose low- ering. Copyright © 2007 S. Karger AG, Basel Introduction It is well known that renal glucose reabsorption is a coordinated process, which takes place in the epithelial cells of the proximal tubule, involving two classes of glu- cose transporters, the Na + -glucose transporters (SGLTs) and facilitative diffusion transporters (GLUTs) [1]. In the early S1 segment, where the bulk of filtered glucose is re- absorbed [2], the low-affinity/high-capacity glucose transporters, SGLT2 and GLUT2, coexpress, respective- ly, in the luminal brush-border membrane (BBM) and in the basolateral membrane (BLM) [3] . Additionally, the presence of GLUT2 protein in the BBM of epithelial tu- Key Words Diabetes  Insulin treatment  Phlorizin treatment  Glucose transporters  GLUT2 Abstract Background/Aims: Increases in the renal glucose transport- er gene expression are involved in renal tubule-glomerular diseases. Here we investigate the GLUT2 gene expression changes in the kidney of diabetic rats, by using insulin or phlorizin treatment. Methods: Rats were rendered diabetic and studied 20 days later: 4–12 h after one single injection of insulin or phlorizin, and 1–6 days after insulin or phlorizin injection twice a day, comparing with diabetic rats injected with placebo. GLUT2 was investigated by Northern and Western analysis. Results: In 20-day diabetic rats, acute treatment with insulin lowered the plasma glucose and in- creased the GLUT2 mRNA (  100%, p ! 0.001) without chang- es in the protein content, while phlorizin lowered the plasma glucose, but changed neither the GLUT2 mRNA nor the pro- tein expression. Twenty-four hours of insulin treatment in- creased both GLUT2 mRNA (  100%, p ! 0.001) and protein (  50%, p ! 0.01), but no effects of phlorizin were observed. After 6 days, insulin and phlorizin similarly reduced glyce- Received: May 31, 2006 Accepted: October 13, 2006 Published online: January 9, 2007 Ubiratan Fabres Machado Department of Physiology and Biophysics, Institute of Biomedical Sciences University of Sao Paulo, Av. Prof. Lineu Prestes, 1524 05505-900, Sao Paulo (SP) (Brazil) Tel. +55 113 091 7494, Fax +55 113 091 7285, E-Mail ubiratan@icb.usp.br © 2007 S. Karger AG, Basel 1660–2137/07/1053–0042$23.50/0 Accessible online at: www.karger.com/nep