Taste cell-expressed α-glucosidase enzymes contribute to gustatory responses to disaccharides

Significance

We previously showed that glucose transporters and the K _ATP metabolic sensor are coexpressed in sweet-responsive taste cells and could serve as sugar sensors in the absence of the sweet receptor (type 1 taste receptors 2 and 3). However, only monosaccharides are substrates for these transporters, whereas dietary carbohydrates are mostly polysaccharides and disaccharides. Here we show that the disaccharide-digesting enzymes maltase-glucoamylase and sucrase-isomaltase are expressed selectively in sweet taste cells. Pharmacological inhibition of these enzymes diminished taste nerve responses only to disaccharides. We hypothesize that these enzymes act in concert with salivary amylase to generate monosaccharide substrates for taste cell-expressed glucose transporters. The transported monosaccharides can then be metabolized to ATP to close K _ATP and activate the T1R-independent sweet taste pathway.

Abstract

The primary sweet sensor in mammalian taste cells for sugars and noncaloric sweeteners is the heteromeric combination of type 1 taste receptors 2 and 3 (T1R2+T1R3, encoded by Tas1r2 and Tas1r3 genes). However, in the absence of T1R2+T1R3 (e.g., in Tas1r3 KO mice), animals still respond to sugars, arguing for the presence of T1R-independent detection mechanism(s). Our previous findings that several glucose transporters (GLUTs), sodium glucose cotransporter 1 (SGLT1), and the ATP-gated K ⁺ (K _ATP) metabolic sensor are preferentially expressed in the same taste cells with T1R3 provides a potential explanation for the T1R-independent detection of sugars: sweet-responsive taste cells that respond to sugars and sweeteners may contain a T1R-dependent (T1R2+T1R3) sweet-sensing pathway for detecting sugars and noncaloric sweeteners, as well as a T1R-independent (GLUTs, SGLT1, K _ATP) pathway for detecting monosaccharides. However, the T1R-independent pathway would not explain responses to disaccharide and oligomeric sugars, such as sucrose, maltose, and maltotriose, which are not substrates for GLUTs or SGLT1. Using RT-PCR, quantitative PCR, in situ hybridization, and immunohistochemistry, we found that taste cells express multiple α-glycosidases (e.g., amylase and neutral α glucosidase C) and so-called intestinal “brush border” disaccharide-hydrolyzing enzymes (e.g., maltase-glucoamylase and sucrase-isomaltase). Treating the tongue with inhibitors of disaccharidases specifically decreased gustatory nerve responses to disaccharides, but not to monosaccharides or noncaloric sweeteners, indicating that lingual disaccharidases are functional. These taste cell-expressed enzymes may locally break down dietary disaccharides and starch hydrolysis products into monosaccharides that could serve as substrates for the T1R-independent sugar sensing pathways.