Sweet taste signaling in the gut

Abstract

The taste system plays a critical role in determining whether a food is nutritious and should be ingested or is potentially toxic and should be rejected (1). Considerable attention has focused on the sweet taste of sugar because it is such a potent stimulator of eating in humans and many other animal species. A major advance in our understanding of sweetness perception was the discovery of two G-coupled receptor proteins, T1R2 and T1R3, which dimerize to form a broadly tuned sweet taste receptor (1). Stimulation of the T1R2+T1R3 taste receptor by sugars or artificial sweeteners activates intracellular signaling elements, including α-gustducin, which stimulate peripheral gustatory nerves and, in turn, brain gustatory pathways. The central processing of the sweet taste signal typically activates feeding circuits as well as brain reward systems that promote sweet appetite (2). Brain autonomic centers may also relay information via the vagus nerve to prepare the digestive system for the incoming carbohydrate-rich food (2). Digestive and absorptive processing of the ingested food is further coordinated by sugar sensing in the intestinal tract, which modulates nutrient absorption, hormone release, and gastrointestinal motility, and generates satiation signals to the brain that terminate the meal (3, 4). In this issue of PNAS, Margolskee et al. (5) report that the same T1R2+T1R3 sweet taste receptor that initiates sugar ingestion in the mouth also detects sugar in the intestinal lumen and triggers physiological responses that promote sugar absorption and metabolism.