Glucagon signaling modulates sweet taste responsiveness

Abstract

The gustatory system provides critical information about the quality and nutritional value of food before it is ingested. Thus, physiological mechanisms that modulate taste function in the context of nutritional needs or metabolic status could optimize ingestive decisions. We report that glucagon, which plays important roles in the maintenance of glucose homeostasis, enhances sweet taste responsiveness through local actions in the mouse gustatory epithelium. Using immunohistochemistry and confocal microscopy, we found that glucagon and its receptor (GlucR) are coexpressed in a subset of mouse taste receptor cells. Most of these cells also express the T1R3 taste receptor implicated in sweet and/or umami taste. Genetic or pharmacological disruption of glucagon signaling in behaving mice indicated a critical role for glucagon in the modulation of taste responsiveness. Scg5(-/-) mice, which lack mature glucagon, had significantly reduced responsiveness to sucrose as compared to wild-type littermates in brief-access taste tests. No significant differences were seen in responses to prototypical salty, sour, or bitter stimuli. Taste responsiveness to sucrose was similarly reduced upon acute and local disruption of glucagon signaling by the GlucR antagonist L-168,049. Together, these data indicate a role for local glucagon signaling in the peripheral modulation of sweet taste responsiveness.

Transformation of postingestive glucose responses after deletion of sweet taste receptor subunits or gastric bypass surgery

“…T1R2 and T1R3 gene-targeted mice (80) were maintained by heterozygote inbreeding. Brief access taste tests (15,20) were used to confirm sweet taste ageusia in these lines. Sprague-Dawley rats were ϳ500 g and aged 18 wk at the time of surgeries (see below).…”

Ingestion of bacterial lipopolysaccharide inhibits peripheral taste responses to sucrose in mice

“…Appetite-modulating hormones cholecystokinin (CCK) (Gosnell and Hsiao, 1984, Herness et al, 2002, Simon et al, 2003, Shen et al, 2005), vasoactive intestinal peptide (Shen et al, 2005), neuropeptide Y (Zhao et al, 2005), oxytocin (Sinclair et al, 2010), leptin (Kawai et al, 2000, Shigemura et al, 2004), endocannabinoids (Yoshida et al, 2010), glucagon (Elson et al, 2010), and glucagon-like peptide (GLP)-1 (Shin et al, 2008) can affect peripheral taste function. Among this group, endocannabinoids, glucagon, and GLP-1 specifically enhance sensitivity to sweet stimuli, contrary to the inhibitory effects on sucrose responses that we observed.…”

“…More recently, however, leptin was reported to increase CT responses to sweet stimuli, perhaps due to a warmer stimulus temperature that likely activated transient receptor potential (TRP)M5 temperature-sensitive pathways (Lu et al, 2012). Each of the hormones listed above modulate appetite by acting on distant receptors, including those on subsets of type II sweet-sensitive taste cells or intragemmal afferent fibers (Kawai et al, 2000, Shigemura et al, 2004, Shin et al, 2008, Elson et al, 2010, Yoshida et al, 2010). As such, they offer a putative link between LPS consumption and Tas1r2/3-mediated suppression of sweet taste function.…”

Lack of glucagon receptor signaling and its implications beyond glucose homeostasis

“…Glucagon and its receptor are coexpressed in a subset of mouse taste receptor cells that express T1R3 taste receptor implicated in sweet and/or umami taste (Elson et al 2010). No major alterations in taste have been described in Gcgr K/K mouse models.…”