Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells.

Caffeine, generally known as a stimulant of gastric acid secretion (GAS), is a bitter-tasting compound that activates several taste type 2 bitter receptors (TAS2Rs). TAS2Rs are expressed in the mouth and in several extraoral sites, e.g., in the gastrointestinal tract, in which their functional role still needs to be clarified. We hypothesized that caffeine evokes effects on GAS by activation of oral and gastric TAS2Rs and demonstrate that caffeine, when administered encapsulated, stimulates GAS, whereas oral administration of a caffeine solution delays GAS in healthy human subjects. Correlation analysis of data obtained from ingestion of the caffeine solution revealed an association between the magnitude of the GAS response and the perceived bitterness, suggesting a functional role of oral TAS2Rs in GAS. Expression of TAS2Rs, including cognate TAS2Rs for caffeine, was shown in human gastric epithelial cells of the corpus/fundus and in HGT-1 cells, a model for the study of GAS. In HGT-1 cells, various bitter compounds as well as caffeine stimulated proton secretion, whereby the caffeine-evoked effect was (i) shown to depend on one of its cognate receptor, TAS2R43, and adenylyl cyclase; and (ii) reduced by homoeriodictyol (HED), a known inhibitor of caffeine's bitter taste. This inhibitory effect of HED on caffeine-induced GAS was verified in healthy human subjects. These findings (i) demonstrate that bitter taste receptors in the stomach and the oral cavity are involved in the regulation of GAS and (ii) suggest that bitter tastants and bitter-masking compounds could be potentially useful therapeutics to regulate gastric pH.

Biscuits with No Added Sugar Containing Stevia, Coffee Fibre and Fructooligosaccharides Modifies α-Glucosidase Activity and the Release of GLP-1 from HuTu-80 Cells and Serotonin from Caco-2 Cells after In Vitro Digestion.

This study assessed the in vitro effects of the bioaccessible food components released during the simulated human digestion of a coffee fibre-containing biscuit (CFB) on α-glucosidase activity, antioxidant capacity and satiety hormones. Digest of CFB presented a significantly (p < 0.05) lower amount of sugar (68.6 mg/g) and a higher antioxidant capacity (15.1 mg chlorogenic acid eq./g) than that of a sucrose-containing biscuit (SCB). The CFB significantly reduced (p < 0.05) α-glucosidase activity (IC50 = 3.3 mg/mL) compared to the SCB (IC50 = 6.2 mg/mL). Serotonin and glucagon-like peptide-1 (GLP-1) release by differentiated Caco-2 and HuTu-80 cells, respectively, was stimulated by the CFB (355% at a concentration of 0.5 mg/mL and 278% at a concentration of 0.05 mg/mL) to the same order of magnitude as those of the SCB. To summarize, the CFB was demonstrated to reduce monosaccharide bioaccessibility, to inhibit a diabetes-related digestive enzyme, and to improve the release of satiety hormones.

N-methylpyridinium, a degradation product of trigonelline upon coffee roasting, stimulates respiratory activity and promotes glucose utilization in HepG2 cells.

N-Methylpyridinium (NMP) is a thermal degradation product of trigonelline formed upon coffee roasting and hypothesized to exert several health benefits in humans. Since for trigonelline evidence for hypoglycemic effects exists, we examined whether NMP also affects mechanisms of glucose utilization and cellular energy formation. For this purpose, the impact of trigonelline and NMP on respiratory activity, extracellular acidification, cellular adenosine nucleotides, energy supply from fatty acids and glucose as well as thermogenesis in HepG2 cells was analyzed. A 24 hour incubation with nanomolar concentrations of NMP enhanced oxygen consumption rates, resulting in increased ATP levels. Glucose was identified as the prevalent energy substrate as its uptake was augmented up to 18.1% ± 7.44% by NMP at 0.09 µM, whereas the uptake of fatty acids decreased upon NMP treatment. Cellular glucose uptake was also stimulated by trigonelline administration; however, a shift to the anaerobic energy production pathway was monitored. Both pyridine derivatives induced thermogenesis, although trigonelline presumably promoted proton leaks, while NMP increased the concentration of the uncoupling protein-2. We provide evidence that both compounds appear to stimulate cellular energy metabolism in HepG2 cells. Human intervention studies are warranted to ensure these effects in vivo.