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

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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.