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Functional studies on the impact of protein kinases on the segmental regulation of electrogenic glucose transport in porcine small intestines

蛋白激酶对猪小肠生电葡萄糖转运节段性调节影响的功能研究

基本信息

批准号：
249232356
负责人：
Dr. Jens Herrmann
金额：
--
依托单位：
Institut für Physiologie und Zellbiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2016-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/249232356?language=en
关键词：
Functional studies impact protein kinases

项目摘要

Pigs can be kept on diets similar to humans and their gastrointestinal tract displays high similarity to man. With regard to a world-wide increase in human diet-related diseases they appear to be more suitable as animal model compared with usually used rodents. But to date it is almost unknown if pigs developed functional and regulative mechanisms matching in detail with human digestive physiology. Our working group observed segmental differences (jejunum vs. ileum) in efficiency of intestinal glucose transport in pigs which did not correlate with respective expression levels of the relevant transporter SGLT1. This proposal focuses on the short-term modulation of SGLT1 mediated absorption of the essential energy source glucose in the porcine jejunum and ileum by induced activation or inhibition of three protein kinases. Responses will be detected functionally by transport physiological tools as Ussing chambers and uptake rates of a glucose equivalent into brush border membrane vesicles. Additionally, changes in expression levels or phosphorylation status of intracellular signalling molecules or SGLT1 will be determined. The data generated by this proposal might provide support for usage of pigs as an animal model for human digestion related research and will elucidate basal regulatory mechanisms of intestinal glucose absorption in more detail.

猪可以吃类似于人类的食物，它们的胃肠道与人类有很高的相似性。关于世界范围内与饮食有关的疾病的增加，与通常使用的啮齿动物相比，它们似乎更适合作为动物模型。但到目前为止，猪是否发展出与人类消化生理相匹配的功能和调节机制几乎是未知的。我们的工作组观察到猪肠道葡萄糖运输效率的节段性差异(空肠和回肠)，这与相关转运体SGLT1的各自表达水平无关。本研究的重点在于SGLT1通过诱导或抑制三种蛋白激酶的激活或抑制来短期调节猪空肠和回肠对必需能量来源葡萄糖的吸收。反应将通过运输生理工具，如Ussing小室和葡萄糖当量的摄取率进入刷状边缘膜小泡来检测。此外，还将确定细胞内信号分子或SGLT1的表达水平或磷酸化状态的变化。这一建议产生的数据可能为将猪作为人类消化相关研究的动物模型提供支持，并将更详细地阐明肠道葡萄糖吸收的基本调节机制。