Modulation of taste sensitivity by GLP‐1 signaling

Abstract

1These authors contributed equally to the work.Abbreviations used: 5-HT, serotonin or 5-hydroxytryptamine; CA, citric acid; CHO, Chinese hamster ovary; CV, circumvallate papillae; DB, denatonium benzoate; GLP-1, glucagon-like peptide 1; GLP-1R, GLP-1 receptor; KO, knockout; PC, proconvertase; PGP 9.5, protein gene product 9.5; PKD2 L1, polycystic kidney disease 2-like 1; TC, taste cell; WT, wild-type. AbstractIn many sensory systems, stimulus sensitivity is dynamically modulated through mechanisms of peripheral adaptation, efferent input, or hormonal action. In this way, responses to sensory stimuli can be optimized in the context of both the environment and the physiological state of the animal. Although the gustatory system critically influences food preference, food intake and metabolic homeostasis, the mechanisms for modulating taste sensitivity are poorly understood. In this study, we report that glucagon-like peptide-1 (GLP-1) signaling in taste buds modulates taste sensitivity in behaving mice. We find that GLP-1 is produced in two distinct subsets of mammalian taste cells, while the GLP-1 receptor is expressed on adjacent intragemmal afferent nerve fibers. GLP-1 receptor knockout mice show dramatically reduced taste responses to sweeteners in behavioral assays, indicating that GLP-1 signaling normally acts to maintain or enhance sweet taste sensitivity. A modest increase in citric acid taste sensitivity in these knockout mice suggests GLP-1 signaling may modulate sour taste, as well. Together, these findings suggest a novel paracrine mechanism for the regulation of taste function.

Liraglutide alters DPP4 in the circumvallate papillae of type 2 diabetic rats

“…Shin and coworkers found that GLP1 and GLP1R are expressed in rat taste buds, and Glp1r-knockout mice showed dramatically reduced taste responses to sweeteners in behavioral assays, which indicated that Glp1 signaling normally acts to maintain or enhance sweet taste sensitivity (Shin et al 2008). We observed upregulation of proglucagon in CV of T2DM-C rats.…”

“…The duration of action of liraglutide is sufficient to enable once-daily administration by subcutaneous injection for the treatment of T2DM and obesity (Degn et al 2004, Raun et al 2007; however, the exact mechanisms by which liraglutide induces weight loss and appetite suppression are not fully understood. Recently, we and other groups independently found that GLP1 and GLP1R are expressed in the taste buds of both animals and humans, that GLP1 signaling acts to modulate sweet, sour, and umami taste sensitivity (Feng et al 2008, Shin et al 2008, Martin et al 2009, and that there are significant differences in these parameters in diabetic and/or obese individuals (Feng et al 2012, Zhang et al 2013. Collectively, these findings indicate that GLP1 is an important peptide for the regulation of taste senses.…”

“…However, previous studies evaluating the expression of DPP4 in the taste buds have revealed conflicting results. Shin and coworkers (Shin et al 2008) showed that little or no DPP4 was expressed in the taste Table 3 Changes in blood chemistry parametes in the three groups of rats. buds of the rat CV, whereas Dubový (1988) suggested that DPP4 is expressed in the taste buds and nerve structures of the cat fungiform papillae.…”

“…Although the mechanism is likely complex and remains unclear, the final effects of the local changes in DPP4 expression secondary to liraglutide treatment are undoubtedly beneficial not only with respect to appetite suppression but also for maintaining energy balance; indeed, there is substantial clinical evidences to support this idea. GLP1 and GLP1R are expressed in the taste buds of all mammals, indicating a paracrine rather than endocrine mechanism of action, and local GLP1 signaling normally acts to maintain or enhance sweet taste sensitivity, thus providing a peripheral mechanism for the reduction of ingestive behaviors and appetite in the context of an animal's metabolic state (Shin et al 2008). Therefore, the increased expression of DPP4 and proglucagon in the CV of T2DM rats after liraglutide treatment may reflect its role in satiety, weight loss, and glucose lowering, with a mechanism that likely involves interaction among paracrine, peripheral sensors, and the central nervous system.…”

Taste perception, associated hormonal modulation, and nutrient intake

“…Hormones that bind to receptors on taste cells alter the palatability of food and, therefore, intake. Current knowledge of the hormonal modulation of taste function is summarized in Table 1 [60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77] and described in greater detail below.…”