Effects of type-2 diabetes and troglitazone on the expression patterns of small intestinal sugar transporters and PPAR-gamma in the Zucker diabetic fatty rat

Background/Aims: We have used the Zucker diabetic fatty (ZDF) rat to study the effects of type-2 diabetes and troglitazone on the small intestinal muc osal mass, sugar transporters a nd the peroxisomal proliferator-activated r eceptor, PPAR-gamma. Methods: Age-matched ZDF and lean control (ZLC) rats w ere fed a standard chow or a troglitazone-enriched diet for 6 weeks. The mu cosa of the small intestines were then extracted, weighed, and SGLT1, GLUT2 , GLUT5 and PPAR-gamma mRNA expression levels assessed by Northern blotting . In the same animal groups, Western blotting and immunohistochemistry were used to study SGLT1, GLUT2 and GLUT5 protein expression levels and targeti ng. Results: The ZDF rat small intestinal mucosal mass was 60% greater than the ZLC rat. However, the expression levels of SGLT1, GLUT2, GLUT5 mRNA an d protein, and PPAR-gamma mRNA in the ZDF and ZLC rats were the same. In ad dition, the targeting of brush-border GLUT5 and basolateral GLUT2 protein i n the ZDF and ZLC rats were the same. Troglitazone treatment reduced SGLT1 mRNA and protein expression levels by 50% in ZDF and ZLC rats, but had no e ffect on mucosal mass or the expression levels of GLUT2 mRNA and protein, G LUT5 mRNA, and PPAR-gamma mRNA. The expression levels of GLUT5 protein in t roglitazone-treated ZLC rats were unchanged when compared to untreated ZLC rats. However, GLUT5 protein expression levels in the troglitazone-treated ZDF rats were 50% below the untreated ZDF rats. Conclusions: Hyperphagia an d insulin are the chronic regulators of small intestinal mucosal mass and s ugar transporter expression patterns, respectively. Furthermore, troglitazo ne suppresses SGLT1 expression at the transcriptional level and GLUT5 at th e post-translational level, independent of changes in glycemia or PPAR-gamm a gene expression. Copyright (C) 2001 S. Karger AG, Basel.