Role of intestinal bitter sensing in enteroendocrine hormone secretion and metabolic control

Abstract

The gastrointestinal tract stores ingested nutrients in the stomach which are then delivered to the small intestine at a controlled rate to optimize their digestion and absorption. The interaction of nutrients with the small and large intestine generates feedback that slows gastric emptying, induces satiation, and reduces postprandial glycemic excursions. The mechanisms underlying these nutrient-gut interactions are complex; it has only recently been appreciated that the gut has the capacity to detect intraluminal contents in much the same way as the tongue, via activation of specific G-protein-coupled receptors, and that ensuing signaling mechanisms modulate the release of an array of gut hormones that influence gastrointestinal motility, appetite and glycemia. Interestingly, evidence from preclinical models supports a functional link between intestinal bitter taste receptor (BTRs) and gastrointestinal hormone secretion, and the outcomes of recent studies indicate that stimulation of intestinal BTRs may be used to modulate gastrointestinal function, to diminish energy intake and limit postprandial blood glucose excursions in humans. This review summarizes current evidence about the expression and function of intestinal BTRs in relation to enteroendocrinehormonereleaseanddiscussestheclinicalimplicationsofthispathway for the management of obesity and type 2 diabetes.