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.
OBJECTIVE
We have used the Zucker diabetic fatty (ZDF) rat to study the effects of type-2 diabetes and troglitazone on the small intestinal mucosal mass, sugar transporters and the peroxisomal proliferator-activated receptor, PPAR-gamma.


METHODS
Age-matched ZDF and lean control (ZLC) rats were fed a standard chow or a troglitazone-enriched diet for 6 weeks. The mucosa 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 targeting.


RESULTS
The ZDF rat small intestinal mucosal mass was 60% greater than the ZLC rat. However, the expression levels of SGLT1, GLUT2, GLUT5 mRNA and protein, and PPAR-gamma mRNA in the ZDF and ZLC rats were the same. In addition, the targeting of brush-border GLUT5 and basolateral GLUT2 protein in 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 effect on mucosal mass or the expression levels of GLUT2 mRNA and protein, GLUT5 mRNA, and PPAR-gamma mRNA. The expression levels of GLUT5 protein in troglitazone-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 and insulin are the chronic regulators of small intestinal mucosal mass and sugar transporter expression patterns, respectively. Furthermore, troglitazone suppresses SGLT1 expression at the transcriptional level and GLUT5 at the post-translational level, independent of changes in glycemia or PPAR-gamma gene expression.
Corpe
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Department of Medicine, University of Chicago, Ill., USA. cpc4@psu.edu
Sreenan
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Burant
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D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002839:Chromans / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D000077288:Troglitazone
D002839:Chromans; D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; D007004:Hypoglycemic Agents; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone