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
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
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DOI：
10.1159/000051879
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发表时间：
2001-01-01
期刊：
影响因子：
3.2
通讯作者：
Burant, C
中科院分区：
文献类型：
--
作者：
Corpe, C;Sreenan, S;Burant, C
背景/目的：我们利用Zucker糖尿病脂肪大鼠（ZDF）研究了2型糖尿病和曲格列酮对小肠黏膜质量、糖转运蛋白和过氧化物酶体增殖物激活受体ppar - γ的影响。方法：年龄匹配的ZDF大鼠和瘦肉对照（ZLC）大鼠分别饲喂标准饲料或富含曲格列酮的饲料6周。提取小肠黏膜，称重，Northern blotting检测SGLT1、GLUT2、GLUT5和ppar - γ mRNA表达水平。在同一动物组中，采用Western blotting和免疫组织化学方法研究SGLT1、GLUT2和GLUT5蛋白的表达水平和靶向性。结果：ZDF大鼠小肠黏膜体积比ZLC大60%。而SGLT1、GLUT2、GLUT5 mRNA和蛋白以及ppar - γ mRNA在ZDF和ZLC大鼠中的表达水平相同。此外，ZDF和ZLC大鼠的刷边GLUT5和基底边GLUT2蛋白的靶向性相同。曲格列酮处理使ZDF和ZLC大鼠的SGLT1 mRNA和蛋白表达水平降低了50%，但对粘膜质量、GLUT2 mRNA和蛋白、GLUT5 mRNA和ppar - γ mRNA的表达水平没有影响。曲格列酮处理的ZLC大鼠与未处理的ZLC大鼠相比，GLUT5蛋白的表达水平没有变化。然而，在曲格列酮处理的ZDF大鼠中，GLUT5蛋白表达水平比未处理的ZDF大鼠低50%。结论：贪食和胰岛素分别是小肠黏膜肿块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上抑制SGLT1表达，在翻译后水平上抑制GLUT5表达，而不依赖于血糖或ppar - γ基因表达的变化。版权所有(C) 2001 S. Karger AG，巴塞尔
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 a nd 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. Copyright (C) 2001 S. Karger AG, Basel.