Many physiological functions in the gastro-entero-pancreatic region such as acid, pepsin and hormone secretion in the stomach and insulin and glucagon release in the islets are finely tuned and regulated by an interplay between several stimuli, including hormonal, paracrine and neuronal signals. Regulatory (or neurohormonal) peptides are known to act as such signals.
Two or more peptides may coexist in one and the same cell or neuron, and may coexist with "classical" transmitters, such as amines and acetylcholine. Furthermore, each regulatory peptide, or other messenger, may have several receptors, usually of the 7TM type.
We use mainly histochemical techniques, such as ICC and ISH in combination with image analysis, to monitor the expression of regulatory peptides, transmitter enzymes, and receptors, and their mRNAs. This enables us to define their cellular localization and how they are regulated.
The level of activity of the target cells, e.g. the beta-cells, can also be monitored, e.g. after exposure to a peptide or other messenger. In order to define the role of a single messenger or receptor, transgenic mice are used. We also use several genetic and nutritional models for type-2 diabetes. We have previously studied the role of the regulatory peptides IAPP, NPY, PYY and PACAP, and their receptors, for islet and gastrointestinal functions. Ghrelin is expressed in a novel (5th) islet cell in rodents and humans, and inhibits insulin secretion from clonal beta-cells. CART is widely expressed in rodent islet cells at birth, and reappears in the beta-cells in rat models of type-2 diabetes. As sudied on clonal beta-cells and isolated rat islets CART augments GLP?1 mediated GSIS, by way of the PKA-dependent pathway.
In order to understand the fine tuning of functions such as islet hormone secretion and islet cell growth it is important to know which regulatory peptides and other messengers and which of their receptors are involved. Further, the intracellular pathways used for their actions are equally important. The knowledge obtained is of special relevance for type-2 diabetes and its treatment