Role of nutrient-sensing taste 1 receptor (T1R) family members in gastrointestinal chemosensing

Abstract

Luminal nutrient sensing by G-protein-coupled receptors (GPCR) expressed on the apical domain of enteroendocrine cells activates intracellular pathways leading to secretion of gut hormones that control vital physiological processes such as digestion, absorption, food intake and glucose homeostasis. The taste 1 receptor (T1R) family of GPCR consists of three members: T1R1; T1R2; T1R3. Expression of T1R1, T1R2 and T1R3 at mRNA and protein levels has been demonstrated in the intestinal tissue of various species. It has been shown that T1R2-T1R3, in association with G-protein gustducin, is expressed in intestinal K and L endocrine cells, where it acts as the intestinal glucose (sweet) sensor. A number of studies have demonstrated that activation of T1R2-T1R3 by natural sugars and artificial sweeteners leads to secretion of glucagon-like peptides 1&2 (GLP-1 and GLP-2) and glucose dependent insulinotropic peptide (GIP). GLP-1 and GIP enhance insulin secretion; GLP-2 increases intestinal growth and glucose absorption. T1R1-T1R3 combination co-expressed on the apical domain of cholecystokinin (CCK) expressing cells is a luminal sensor for a number of L-amino acids; with amino acid-activation of the receptor eliciting CCK secretion. This article focuses on the role of the gut-expressed T1R1, T1R2 and T1R3 in intestinal sweet and L-amino acid sensing. The impact of exploiting T1R2-T1R3 as a nutritional target for enhancing intestinal glucose absorption and gut structural maturity in young animals is also highlighted.

The Physiology of Taste in Fish: Potential Implications for Feeding Stimulation and Gut Chemical Sensing

“…Their activation by sweet ligands in L and K cells leads to the release of glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) and glucose-dependent insulinotropic peptide (GIP), which in turn enhance insulin secretion from pancreatic b-cells, glucose absorption (upregulation of Na C -glucose cotransporter 1) and intestinal growth (Jang et al, 2007;Margolskee et al, 2007). As a result of these positive effects, artificial sweeteners are nowadays commonly used in intensive livestock production, particularly in early-weaning piglet diets, to enhance gut structural maturity and avoid problems of nutrient malabsorption, diarrhea, malnutrition, and dehydration commonly observed at this stage (Shirazi-Beechey et al, 2014). Furthermore, T1R1, T1R3, G agust , and cholecystokinin (CCK) are coexpressed in enteroendocrine I cells and activation of the umami receptor dimer by several L-AAs (but not by D-isomers) stimulates CCK secretion, an anorexigenic peptide that inhibits food intake, slows gastric emptying and stimulates pancreatic and gallbladder secretions (Daly et al, 2013).…”

Glucagon-like peptide 2 and its beneficial effects on gut function and health in production animals

“…Vagal efferent nerves and enteric neurons then induce GLP-2 release from L cells located in the distal small intestine and colon via acetylcholine and gastrin-releasing peptide. The second peak in GLP-2 release occurs 60 to 120 min after a meal through direct nutrient stimulation of L cells [53] by activation of specialized G-protein-coupled receptors present on their apical surfaces, which act as luminal chemosensors or "taste" receptors [55,56]. The L cells express multiple types of chemosensors that are specifically activated by nutrients and sensory factors that stimulate GLP-2 secretion, including amino acids and peptones (via receptors T1R1-T1R3, CaSR, and LPAR5), bile acids (via receptor TGR5), simple sugars and non-nutritive sweeteners (via receptor T1R2-T1R3), free fatty acids and their metabolites (via receptors GPR40, GPR41, GPR43, GPR119, and GPR120), and bitter substances (via numerous taste receptor type 2 receptors; [52,57]).…”

Recent Advances in Fatty Acid Perception and Genetics

“…This concept is not unique to FA receptors. Bitter and sweet taste receptors were identified by their role in taste perception in the mouth but function in other parts of the body as well (29)(30)(31)(32)(33)(34)(35). The reverse strategy may work for fat taste: FA signaling.…”