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

猪的饮食与人类相似，它们的胃肠道也与人类非常相似。考虑到世界范围内人类饮食相关疾病的增加，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。但迄今为止，几乎不知道猪是否发育出与人类消化生理相匹配的功能和调节机制。我们的工作组观察到猪肠道葡萄糖转运效率的节段差异（空肠与回肠），这与相关转运体SGLT1各自的表达水平无关。本研究的重点是通过诱导激活或抑制三种蛋白激酶，短期调节SGLT1介导的猪空肠和回肠中必需能量源葡萄糖的吸收。反应将通过运输生理工具进行功能检测，如使用腔室和葡萄糖当量进入刷状膜囊泡的摄取速率。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。本研究产生的数据可能为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。

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.