The noncaloric sweeteners (NCSs) cyclamate (Cycl) and acesulfame K (AceK) are widely added to foods and beverages. Little is known about their impact on gastric acid secretion (GAS), which is stimulated by dietary protein and bitter-tasting compounds. Since Cycl and AceK have a bitter off taste in addition to their sweet taste, we hypothesized they modulate mechanisms of GAS in human gastric parietal cells (HGT-1). HGT-1 cells were exposed to sweet tastants (50 mM of glucose, d-threonine, Cycl, or AceK) and analyzed for their intracellular pH index (IPX), as an indicator of proton secretion by means of a pH-sensitive dye, and for mRNA levels of GAS-associated genes by RT-qPCR. Since the NCSs act via the sweet taste-sensing receptor T1R2/T1R3, mRNA expression of the corresponding genes was analyzed in addition to immunocytochemical localization of the T1R2 and T1R3 receptor proteins. Exposure of HGT-1 cells to AceK or d-threonine increased the IPX to 0.60 ± 0.05 and 0.80 ± 0.04 ( P ≤ 0.05), respectively, thereby indicating a reduced secretion of protons, whereas Cycl demonstrated the opposite effect with IPX values of -0.69 ± 0.08 ( P ≤ 0.05) compared to controls (IPX = 0). Cotreatment with the T1R3-inhibitor lactisole as well as a TAS1R3 siRNA knock-down approach reduced the impact of Cycl, AceK, and d-thr on proton release ( P ≤ 0.05), whereas cotreatment with 10 mM glucose enhanced the NCS-induced effect ( P ≤ 0.05). Overall, we demonstrated Cycl and AceK as modulators of proton secretion in HGT-1 cells and identified T1R3 as a key element in this response.

Secretion of gastric acid, aimed at preventing bacterial growth and aiding the digestion of foods in the stomach, is chiefly stimulated by dietary intake of protein and amino acids (AAs). However, AAs' key structural determinants responsible for their effects on mechanisms regulating gastric acid secretion (GAS) have not been identified yet. In this study, AAs have been tested in the parietal cell model HGT-1 on GAS and on mRNA expression of genes regulating GAS. AAs' taste intensities from 0 (not bitter at all) to 10 (very bitter) were assessed in a sensory study, in which ARG (l: 6.42 ± 0.41; d: 4.62 ± 0.59) and ILE (l: 4.21 ± 0.43; d: 2.28 ± 0.33) were identified as bitter-tasting candidates in both isomeric forms. Pearson correlation showed that GAS in HGT-1 cells is directly associated with the bitter taste quality ( r: -0.654) in combination with the molecular weight of l-AA ( r: -0.685).

ScopeIncreasing the intake of satiety‐enhancing food compounds represents a promising strategy for maintaining a healthy body weight. Recently, satiating effects for the capsaicinoid nonivamide have been demonstrated. As various proteins and amino acids have also been demonstrated to decrease energy intake, oral glucose tolerance test (oGTT)‐based bolus interventions of 75 g glucose + 0.15 mg nonivamide (NV control) are tested with/without combination of a wheat protein hydrolysate (WPH: 2 g) and/or l‐arginine (ARG: 3.2 g) for their satiating effects in 27 moderately overweight male subjects.Methods and ResultsCompared to NV control intervention, ARG and WPH + ARG treatment both reduce (p < 0.01) total calorie intake from a standardized breakfast by –5.9 ± 4.15% and –6.07 ± 4.38%, respectively. For the WPH + ARG intervention, increased mean plasma serotonin concentrations (AUC: 350 ± 218), quantitated by ELISA, and delayed gastric emptying, assessed by 13C‐Na‐acetate breath test (−2.10 ± 0.51%, p < 0.05), are demonstrated compared to NV control. Correlation analysis between plasma serotonin and gastric emptying reveals a significant association after WPH ± ARG intervention (r = –0.396, p = 0.045).ConclusionCombination of WPH and ARG enhances the satiating effect of nonivamide, providing opportunities to optimize satiating food formulations by low amounts of the individual food constituents.

This study aimed at identifying whether the bitter-tasting amino acids l-arginine (l-ARG) and l-isoleucine (l-ILE) differentially regulate mechanisms of gastric acid secretion in human parietal cells (HGT-1 cells) via activation of bitter taste sensing receptors (T2Rs). In a first set of experiments, involvement of T2Rs in l-ARG and l-ILE-modulated proton secretion was demonstrated by co-treatment of HGT-1 cells with T2R antagonists. Subsequent whole genome screenings by means of cDNA arrays revealed T2R1 as a prominent target for both amino acids. Next, the functional role of T2R1 was verified by means of a T2R1 CRISPR-Cas9 knock-out approach. Here, the effect of l-ARG on proton secretion decreased by 65.7 ± 21.9% and the effect of l-ILE increased by 93.2 ± 24.1% in HGT-1 T2R1 ko versus HGT-1 wt cells (p < 0.05). Overall, our results indicate differential effects of l-ARG and l-ILE on proton secretion in HGT-1 cells and our molecular docking studies predict distinct binding for these amino acids in the binding site of T2R1. Further studies will elucidate whether the mechanism of differential effects involves structure-specific ligand-biased signaling of T2R1 or additional cellular targets.