Increased expression of glutathione S-transferase in renal proximal tubules in the early stages of diabetes: A study of type-2 diabetes in the Akita mouse model

Background/Aim: The objective of this study was to examine whether the gene expression profile in the kidney is modified by hyperglycemia in the early stage of diabetes. Methods: We analyzed the expression of kidney mRNAs usi ng cDNA array membranes including 588 genes in the kidney of the Akita mous e, a model of type-2 diabetes, after exposure to hyperglycemia for a modera te length of time, but before the manifestation of diabetic glomerulosclero sis. Western blot analysis and immunohistochemical studies were performed t o confirm whether the protein for the increasingly expressed mRNA was highl y expressed in the kidney of the diabetic mouse. Results: Two of the 10 det ected mRNAs, glutathione S-transferase (GST) alpha and mu, in the kidneys f rom diabetic mice showed a more than twofold increased expression in compar ison to those of control mice. Western blot analysis in kidney tissue extra cts confirmed increases in GST a and tt at protein levels in the diabetic m ice. Immunohistochemical studies revealed strong staining for those protein s in the proximal tubules of diabetic mice. Conclusion: These data collecti vely indicate that expression of GSTs is increased in epithelial cells in p roximal tubules even at the early stage of diabetes, probably in response t o oxidative stress triggered by hyperglycemia or other toxic effects of glu cose. Copyright (C) 2001 S. Karger AG, Basel.