Corpe C, Sreenan S, Burant C
Department of Medicine, University of Chicago, Ill., USA.
Digestion. 2001;63(2):116-23. doi: 10.1159/000051879.
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 mucosal mass, sugar transporters and the peroxisomal proliferator-activated receptor, PPAR-gamma.
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.
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.
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.
背景/目的：我们使用Zucker糖尿病脂肪（ZDF）大鼠来研究2型糖尿病和曲格列酮对小肠黏膜质量、糖转运蛋白以及过氧化物酶体增殖物激活受体PPAR-γ的影响。
将年龄匹配的ZDF大鼠和瘦素对照（ZLC）大鼠分为两组，分别喂食标准饲料或富含曲格列酮的饲料，持续6周。然后提取小肠黏膜，称重，并通过Northern印迹法评估钠-葡萄糖协同转运蛋白1（SGLT1）、葡萄糖转运蛋白2（GLUT2）、葡萄糖转运蛋白5（GLUT5）和PPAR-γ mRNA的表达水平。在相同动物组中，采用蛋白质印迹法和免疫组织化学法研究SGLT1、GLUT2和GLUT5蛋白的表达水平及定位。
ZDF大鼠的小肠黏膜质量比ZLC大鼠大60%。然而，ZDF大鼠和ZLC大鼠中SGLT1、GLUT2、GLUT5 mRNA和蛋白以及PPAR-γ mRNA的表达水平相同。此外，ZDF大鼠和ZLC大鼠中刷状缘GLUT5和基底侧GLUT2蛋白的定位相同。曲格列酮治疗使ZDF大鼠和ZLC大鼠的SGLT1 mRNA和蛋白表达水平降低50%，但对黏膜质量或GLUT2 mRNA和蛋白、GLUT5 mRNA以及PPAR-γ mRNA的表达水平无影响。与未治疗的ZLC大鼠相比，曲格列酮治疗的ZLC大鼠中GLUT5蛋白的表达水平未发生变化。然而，曲格列酮治疗的ZDF大鼠中GLUT5蛋白的表达水平比未治疗的ZDF大鼠低50%。
摄食过多和胰岛素分别是小肠黏膜质量和糖转运蛋白表达模式的慢性调节因子。此外，曲格列酮在转录水平抑制SGLT1的表达，在翻译后水平抑制GLUT5的表达，这与血糖变化或PPAR-γ基因表达无关。
