Regulation of gut hormone secretion. Studies using isolated perfused intestines.

The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from enteroendocrine cells in the intestine along with other gut hormones (PYY, CCK and neurotensin) shown to affect metabolism and/or appetite. The secretion of many gut hormones is highly increased after gastric bypass operations, which have turned out to be an effective therapy of not only obesity but also type 2 diabetes. These effects are likely to be due, at least in part, to increases in the secretion of these gut hormones (except GIP). Therefore, stimulation of the endogenous hormone represents an appealing therapeutic strategy, which has spurred an interest in understanding the regulation of gut hormone secretion and a search for particularly GLP-1 and PYY secretagogues. The secretion of the gut hormones is stimulated by oral intake of nutrients often including carbohydrate, protein and lipid. This review focuses on stimulators of gut hormone secretion, the mechanisms involved, and in particular models used to investigate secretion. A major break-through in this field was the development of methods to identify and isolate specific hormone producing cells, which allow detailed mapping of the expression profiles of these cells, whereas they are less suitable for physiological studies of secretion. Isolated perfused preparations of mouse and rat intestines have proven to be reliable models for dynamic hormone secretion and should be able to bridge the gap between the molecular details derived from the single cells to the integrated patterns observed in the intact animals.