Umami Receptor Activation Increases Duodenal Bicarbonate Secretion via Glucagon-Like Peptide-2 Release in Rats

Wang, Joon Ho; Inoue, Takuya; Higashiyama, Masaaki; Guth, Paul H.; Engel, Eli; Kaunitz, Jonathan D.; Akiba, Yasutada

doi:10.1124/jpet.111.184788

Cited by 66 publications

(72 citation statements)

References 42 publications

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“…This suggests that modification of colonic motility can be achieved by physiological amino acids in the gut. Previous studies in the proximal gut show that certain L-AAs can cause activation of T1R1/T1R3 specifically, while other L-AAs may affect different amino acid-sensing receptors (10,29,43,44). We have shown the effect of activation of the L-AA-sensing T1R1/T1R3 on motility of the distal colon.…”

Section: Discussionmentioning

confidence: 73%

Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

Kendig

Hurst

Bradley

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Kendig DM, Hurst NR, Bradley ZL, Mahavadi S, Kuemmerle JF, Lyall V, DeSimone J, Murthy KS, Grider JR. Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon. Am J Physiol Gastrointest Liver Physiol 307: G1100 -G1107, 2014. First published October 16, 2014; doi:10.1152/ajpgi.00251.2014.-Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5=-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1 Ϫ/Ϫ mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by L-cysteine, but not L-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or L-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion. monosodium glutamate, T1R1/T1R3; motility; human colon; chemosensation THE ABILITY OF INTRALUMINAL nutrients to affect motility of the gastrointestinal (GI) tract has been known for decades (14). However, some of the receptors responsible for sensing intraluminal nutrients have only been discovered very recently. These receptors are the same as those responsible for the detection of taste qualities in the lingual epithelium. Multiple studies show the presence of taste receptors and the associated intracellular signaling molecules in the upper GI tract; however, there is less evidence for the existence of these receptors in the distal gut, specifically, the distal colon (13,37,48). While absorption of nutrients occurs almost completely in the small intestine, amino acids from the diet, dead mucosal cells, digested luminal enzymes, and amino acids generated by bacteria are present in the lumin...

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Section: Discussionmentioning

confidence: 73%

Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

Kendig

Hurst

Bradley

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Since luminal nutrients, including fatty acids, stimulate the production and secretion of GLP-2 in the intestinal mucosa, a HFD may contribute to intestinal tumorigenesis via increased mucosal GLP-2 (33,34). Chronic exposure to a HFD significantly increases the concentration of plasma GLP-2 and intestinal crypt-villus height (35).…”

Section: Discussionmentioning

confidence: 99%

Sitagliptin, a dipeptidyl peptidase-4 inhibitor, suppresses CXCL5 and SDF-1 and does not accelerate intestinal neoplasia formation in ApcMin/+ mice fed a high-fat diet

et al. 2017

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Abstract.The relationship between type 2 diabetes mellitus and intestinal neoplasia has been shown epidemiologically. A high-fat diet (HFD) is also known to promote insulin resistance, which is a risk factor for intestinal neoplasia. Dipeptidyl peptidase-4 (DPP-4) inhibitors are used in the clinic for the treatment of type 2 diabetes and also to prolong the effects of glucagon-like peptide-1 (GLP-1). However, since the intestinotrophic hormone GLP-2 and chemokines, such as CXCL5 and stromal cell-derived factor-1 (SDF-1), are also substrates of DPP-4, DPP-4 inhibitors may increase the risk of intestinal carcinogenesis. In this study, we evaluated the impact of a DPP-4 inhibitor on intestinal tumorigenesis in Apc Min/+ mice fed a HFD. Six-week-old male Apc Min/+ mice were randomized to either a normal diet (10 kcal% fat) group, a HFD (60 kcal% fat) group, or a HFD group treated with sitagliptin (STG). The mice were euthanized nine weeks after the start of treatment. Daily treatment with STG did not increase number of intestinal tumors in the HFD group; however, this increase was not statistically significant. The mucosal concentration of total GLP-2 was significantly increased in the HFD group. The chemokine protein array showed elevated plasma concentrations of CXCL5 and SDF-1 in the HFD group. The administration of STG significantly suppressed the levels of plasma CXCL5 and SDF-1 in mice fed a HFD. Since CXCL5 expression is increased in patients with type 2 diabetes, and GLP-2, CXCL5 and SDF-1 are associated with tumor progression, DPP-4 inhibition may have potential as an agent for decreasing the risk of cancer in obese or diabetic patients.

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“…Although the direct effects of GLP-2 on liver and lung health of livestock have not been evaluated, feeding of aspartate for 20 d to weanling pigs was shown to affect mRNA expression of proinflammatory signaling molecules in the toll-like receptor 4 and nuclear-binding and oligomerization domain pathways that modulate innate and adaptive immune function, and to improve serum indicators of liver damage after an intraperitoneal LPS challenge [109]. Although the mechanism of action of aspartate supplementation and plasma GLP-2 level were not evaluated in their study, feeding of this amino acid has the potential to promote GLP-2 release from intestinal L cells [100,101] through activation of taste receptors (eg, T1R1-T1R3) and could contribute to the positive hepatic effects observed. Given the potential benefits of GLP-2 on liver health, evaluation of GLP-2 for the prevention of hepatic disorders in production animals, such as fatty liver in transition dairy cows, is warranted.…”

Section: Potential Uses Of Glp-2 and Stimulators Of Glp-2 Secretion Imentioning

confidence: 92%

“…Of interest, taste receptor T1R1-T1R3 activation by both L-glutamate and inosine 5 0 -monophosphate increases GLP-2 release in rat duodenum [100], and both GLP-2 administration and a combined treatment of L-alanine with inosine 5 0 -monophosphate increase the healing rate of intestinal ulcers in rats [47]. In addition, Bauchart-Thevret et al [101] demonstrated that dietary monosodium glutamate supplementation of preterm pigs dose-dependently increases plasma GLP-2 concentration.…”

Section: Potential Uses Of Glp-2 and Stimulators Of Glp-2 Secretion Imentioning

confidence: 97%

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

Connor

Evock‐Clover

Wall³

et al. 2016

Domestic Animal Endocrinology

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Numerous endocrine cell subtypes exist within the intestinal mucosa and produce peptides contributing to the regulation of critical physiological processes including appetite, energy metabolism, gut function, and gut health. The mechanisms of action and the extent of the physiological effects of these enteric peptides are only beginning to be uncovered. One peptide in particular, glucagon-like peptide 2 (GLP-2) produced by enteroendocrine L cells, has been fairly well characterized in rodent and swine models in terms of its ability to improve nutrient absorption and healing of the gut after injury. In fact, a long-acting form of GLP-2 recently has been approved for the management and treatment of human conditions like inflammatory bowel disease and short bowel syndrome. However, novel functions of GLP-2 within the gut continue to be demonstrated, including its beneficial effects on intestinal barrier function and reducing intestinal inflammation. As knowledge continues to grow about GLP-2's effects on the gut and its mechanisms of release, the potential to use GLP-2 to improve gut function and health of food animals becomes increasingly more apparent. Thus, the purpose of this review is to summarize: (1) the current understanding of GLP-2's functions and mechanisms of action within the gut; (2) novel applications of GLP-2 (or stimulators of its release) to improve general health and production performance of food animals; and (3) recent findings, using dairy calves as a model, that suggest the therapeutic potential of GLP-2 to reduce the pathogenesis of intestinal protozoan infections.

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Umami Receptor Activation Increases Duodenal Bicarbonate Secretion via Glucagon-Like Peptide-2 Release in Rats

Cited by 66 publications

References 42 publications

Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

Sitagliptin, a dipeptidyl peptidase-4 inhibitor, suppresses CXCL5 and SDF-1 and does not accelerate intestinal neoplasia formation in ApcMin/+ mice fed a high-fat diet

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

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