Charlotte Christensen - The colon as an endocrine organ

This PhD project aims at elucidating endocrine functions of the colon since the colonic epithelium harbors a high number of the endocrine GLP-1 and PYY secreting cells. These are of great interest because of their highly attractive anti-diabetic and anti-obesity effects. We anticipate that several of the colonic mechanisms for secretion are related to those observed in the small intestine.

Consequently, we hypothesize that secretion from colonic endocrine cells is regulated by both luminal factors and neuroendocrine as well as paracrine mechanisms. Knowledge about these mechanisms may give clues to pharmaceutical stimulation of the numerous colonic L-cells as a means to combat T2D and obesity.

In order to approach this hypothesis a single cell secretion study of primary colonocytes will be conducted. However, the major part of this project will focus on the perfused rat colon, which allows us to investigate the isolated effect of relevant factors in the intact organ, while maintaining its normal vascular supply and cell polarity. Small molecule metabolites found in the lumen and vasculature of the rat colon will be identified by metabolomics analysis and subsequently tested in the perfused colon.

Secondly, the impact of metabolic initiators, neural signals, endocrine substrates and paracrine stimuli on colonic hormone secretion will be tested.

Finally, we will investigate the endocrine function of the normal and the pathological colon in vivo, by administrating test substances directly into the colonic lumen.

Overall, the outcome of this project will importantly contribute to a better understanding of hormone secretion from the colon.