Insulin but not phlorizin treatment induces a transient increase in GLUT2 gene expression in the kidney of diabetic rats.

ABSTRACT

BACKGROUND/AIMS: Increases in the renal glucose transporter 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 increased the GLUT2 mRNA ( approximately 100%, p < 0.001) without changes in the protein content, while phlorizin lowered the plasma glucose, but changed neither the GLUT2 mRNA nor the protein expression. Twenty-four hours of insulin treatment increased both GLUT2 mRNA ( approximately 100%, p < 0.001) and protein ( approximately 50%, p < 0.01), but no effects of phlorizin were observed. After 6 days, insulin and phlorizin similarly reduced glycemia, 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 specifically by insulin only. The 6-day normalization of GLUT2, however, was induced by both insulin and phlorizin treatment, which seems to be related to the plasma glucose lowering.