Glucose transporters and ATP-gated K ⁺ (K _ATP ) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells

Abstract

Although the heteromeric combination of type 1 taste receptors 2 and 3 (T1r2 + T1r3) is well established as the major receptor for sugars and noncaloric sweeteners, there is also evidence of T1r-independent sweet taste in mice, particularly so for sugars. Before the molecular cloning of the T1rs, it had been proposed that sweet taste detection depended on ( a ) activation of sugar-gated cation channels and/or ( b ) sugar binding to G protein-coupled receptors to initiate second-messenger cascades. By either mechanism, sugars would elicit depolarization of sweet-responsive taste cells, which would transmit their signal to gustatory afferents. We examined the nature of T1r-independent sweet taste; our starting point was to determine if taste cells express glucose transporters (GLUTs) and metabolic sensors that serve as sugar sensors in other tissues. Using RT-PCR, quantitative PCR, in situ hybridization, and immunohistochemistry, we determined that several GLUTs (GLUT2, GLUT4, GLUT8, and GLUT9), a sodium–glucose cotransporter (SGLT1), and two components of the ATP-gated K + (K ATP ) metabolic sensor [sulfonylurea receptor (SUR) 1 and potassium inwardly rectifying channel (Kir) 6.1] were expressed selectively in taste cells. Consistent with a role in sweet taste, GLUT4, SGLT1, and SUR1 were expressed preferentially in T1r3-positive taste cells. Electrophysiological recording determined that nearly 20% of the total outward current of mouse fungiform taste cells was composed of K ATP channels. Because the overwhelming majority of T1r3-expressing taste cells also express SUR1, and vice versa, it is likely that K ATP channels constitute a major portion of K + channels in the T1r3 subset of taste cells. Taste cell-expressed glucose sensors and K ATP may serve as mediators of the T1r-independent sweet taste of sugars.

Behavioral Evidence for More than One Taste Signaling Pathway for Sugars in Rats

“…Numerous studies have already demonstrated that these differences manifest in the controls of ingestive behavior as well, including the facility to reinforce preferences for associated novel flavors (e.g., Ackroff, 1994, 2012b;Zukerman et al, 2013). Rather, the new finding here is that, following exposure to these respective repertoires, the orosensory properties of glucose were more effective at generating licking than those of fructose in the GvFtrained rats.…”

“…A number of sugar transporters were recently identified in taste tissue, leading some to speculate they may function as auxiliary sugar sensors (Merigo et al, 2011;Toyono et al, 2011;Yee et al, 2011), like they seem to in other tissues (e.g., GI tract and CNS) (Dyer et al, 2003;O'Malley et al, 2006). Because most glucose transporters also mediate galactose, but not fructose, transport (Wright et al, 2012), the same sort of brief access test was conducted with six galactose concentrations (and dH 2 O) in place of Na-saccharin.…”

Lipid-Lowering Pharmaceutical Clofibrate Inhibits Human Sweet Taste

“…This finding could be explained by non-T1R3 mediated sweet taste (Damak et al 2003). K ATP channels are part of a metabolic signaling pathway and are expressed in many taste cells and may contribute to depolarization of these cells and activation of downstream signaling events (Merigo et al 2011;Yee et al 2011). In T1R3 knockout mice, nerve responses to glucose were diminished but not abolished (Damak et al 2003), indicating residual signaling from sugars in mice.…”

Temperature Influences Chorda Tympani Nerve Responses to Sweet, Salty, Sour, Umami, and Bitter Stimuli in Mice

“…The saccharin response at 43 °C was similar to that at 23 °C, while the sucralose response at 43 °C was significantly lower than that at 23 °C. Clearly, high stimulus temperatures compromise CT nerve responses to the 2 artificial sweeteners more than to the 4 sugars, which may reflect the differential effects on the sucrose receptor (T1R2/T1R3), and/or a T1R independent mechanism, such as glucose transporters (Damak et al 2003;Toyono et al 2011;Yee et al 2011).…”