Understanding the release mechanisms and secretion patterns for glucagon-like peptide-1 using the isolated perfused intestine as a model.

Abstract

In the gastrointestinal (GI) tract, food is digested and absorbed while GI hormones are secreted from the enteroendocrine cells (EECs). These hormones regulate food intake, glucose homeostasis, digestion, GI motility, and metabolism. Although ECCs may express more than a single hormone, the ECCs usually secrete only one or a few hormones. The pattern of EEC secretion varies along the length of the GI tract as the different EEC types are scattered in different densities along the GI tract. Following bariatric surgery, a postprandial hypersecretion of certain GI hormones occurs which contributes to the postsurgery weight loss. Mimicking this postprandial hypersecretion of GI hormones by targeting endogenous EEC secretion, using specific modulators of receptors, ion channels, and transporters found on specific EECs, to induce weight loss is a current research aim. To achieve this, a more complete understanding of the release mechanisms, expression of receptors, transporters, and the secretion pattern of the different ECC types is needed. Using the vascularly perfused intestinal model, it is possible to obtain a detailed knowledge of these release mechanisms by evaluating the effects on secretion of blocking or stimulating specific receptors, ion channels, and transporters as well as evaluating nutrient handling and absorption in each of the different sections of the intestine. This mini-review will focus on how the isolated perfused intestine has been used in our group as a model to investigate the nutrient-induced release mechanisms of ECCs with a focus on glucagon-like peptide-1 secreting cells.