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.

Figure 1.

Expression of glucagon signaling components in mouse taste buds. A) RT-PCR of mouse CV and surrounding nontaste tissue (NTT). B–D) Coexpression of glucagon and GlucR in the same subset of TRCs in CV (B), foliate (C), and fungiform (D) papillae. E) GlucR and 7B2 are coexpressed in a subset of TRCs in CV papillae. F) GlucR staining in TRCs is absent in GlucR^−/− mice. Scale bars: 10 μm (B–E); 50 μm (F).

Figure 2.

Glucagon and GlucR are expressed in a subset of type II TRCs. A) Glucagon and GlucR are not expressed in 5HT⁺ TRCs. B) GlucR is expressed in a subset of PLCβ2⁺ TRCs. C) Partial overlap of GlucR and α-gustducin expression in TRCs. D) Glucagon and T1R3 coexpression in TRCs. E) T1R3 staining in TRCs is absent in T1R3^−/− mice. Scale bars = 10 μm. All sections are from mouse CV.

Figure 3.

Altered sweet taste responses of Scg5^−/− mice in brief access taste tests. A, B) 7B2 is expressed in Scg5^+/+ (A) but not Scg5^−/− (B) mice. C, D) Glucagon is produced in Scg5^+/+ (C) but not Scg5^−/− (D) mice. E–H) Taste responses, expressed as taste/water-lick ratios and as a function of stimulus concentration, of Scg5^−/− (red; n=7) and Scg5^+/+ littermates (black; n=9) to sucrose (E), NaCl (F), DB (G), and CA (H). Scg5^−/− mice exhibited a reduced responsiveness to sucrose (P=0.01) but not to the other taste stimuli. Points are expressed as means ± se. Dashed reference line indicates lick ratio for water (1.0). Scale bars = 10 μM.

Figure 4.

Reduced sweet taste responses in the presence of a GlucR antagonist. A) Mice show neither preference nor aversion to ascending concentrations of L-168,049 (n=6). To best test for an aversive taste, mice are deprived of water prior to testing. B–E) Taste responses, expressed as taste/water-lick ratios and as a function of stimulus concentration, of drug-treated (red) and vehicle-treated (61) C57BL/6J mice to sucrose (L-168,049-treated, n=9; vehicle-treated, n=11; B), NaCl (L-168,049-treated, n=5; vehicle-treated, n=5; C), DB (L-168,049-treated, n=10; vehicle-treated, n=10; D), and CA (L-168,049-treated, n=10; vehicle-treated, n=10; E). L-168,049-treated mice exhibited reduced responsiveness to sucrose only (P=0.02). Points are expressed as means ± se. Dashed reference line indicates lick ratio for water (1.0).