Abstract
The taste stimulus glucose comprises approximately half of the commercial sugar sweeteners used today, whether in the form of the di-saccharide sucrose (glucose-fructose) or half of high-fructose corn syrup (HFCS). Therefore, oral glucose has been presumed to contribute to the sweet taste of foods when combined with fructose. In light of recent rodent data on the role of oral metabolic glucose signaling, we examined psychopharmacologically whether oral glucose detection may also involve an additional pathway in humans to the traditional sweet taste transduction via the class 1 taste receptors T1R2/T1R3. In a series of experiments, we first compared oral glucose detection thresholds to sucralose thresholds without and with addition of the T1R receptor inhibitor Na-lactisole. Next, we compared oral detection thresholds of glucose to sucralose and to the non-metabolizable glucose analog, α-methyl-D-glucopyranoside (MDG) without and with the addition of the glucose co-transport component sodium (NaCl). Finally, we compared oral detection thresholds for glucose, MDG, fructose, and sucralose without and with the sodium-glucose co-transporter (SGLT) inhibitor phlorizin. In each experiment, psychopharmacological data were consistent with glucose engaging an additional signaling pathway to the sweet taste receptor T1R2/T1R3 pathway. Na-lactisole addition impaired detection of the non-caloric sweetener sucralose much more than it did glucose, consistent with glucose using an additional signaling pathway. The addition of NaCl had a beneficial impact on the detection of glucose and its analog MDG and impaired sucralose detection, consistent with glucose utilizing a sodium-glucose co-transporter. The addition of the SGLT inhibitor phlorizin impaired detection of glucose and MDG more than it did sucralose, and had no effect on fructose, further evidence consistent with glucose utilizing a sodium-glucose co-transporter. Together, these results support the idea that oral detection of glucose engages two signaling pathways: one that is comprised of the T1R2/T1R3 sweet taste receptor and the other that utilizes an SGLT glucose transporter.
Highlights
The oral detection of sugars is presumed to occur by activation of a class 1 taste receptor heteromer, TAS1R2-TAS1R3, sometimes referred to as a ‘sweetener receptor’ [1,2,3,4,5]
We predicted that inhibiting the T1R2-T1R3 taste signal with the T1R inhibitor Nalactisole would have a greater impact on sucralose than it would on glucose detection thresholds
The pharmacological sodium-glucose co-transporter (SGLT) inhibitor phlorizin had a profound impact on impeding every subject’s ability to detect glucose and MDG but did not impede their detection of fructose nor sucralose, further supporting the idea that oral glucose signaling involves a second pathway involving SGLT. These rinse-and-expectorate experiments point to the ability of humans to sense glucose orally via a signaling pathway that includes the sodium-glucose cotransporters (SGLTs)
Summary
The oral detection of sugars is presumed to occur by activation of a class 1 taste receptor heteromer, TAS1R2-TAS1R3, sometimes referred to as a ‘sweetener receptor’ [1,2,3,4,5]. Despite the century-long refinement of no-calorie or low-caloric sweeteners in beverages, diet sodas have never captured a major share of the beverage market [13]. Reasons for this are presently unknown, but have been attributed to: 1) non-sucrose-like sweetness, 2) non-sucroselike bitterness and other side tastes, 3) non-sucrose-like temporal profile of sweetness (lingering taste) [14], 4) customer fears of artificial ingredients in foods (naturalism bias) [15], and 5) concerns for increased risk of medical pathologies from use, such as cancer [16, 17]. We hypothesize an additional explanation that sugars may engage a second oral signaling pathway for calories that noncaloric sweeteners fail to engage [18, 19]
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