Suppression of Oral Sweet Sensations during Consumption of Sweet Food in Humans: Effects on Gastric Emptying Rate, Glycemic Response, Appetite, Food Satisfaction and Desire for Basic Tastes.

Suppression of oral sweet sensation (OSS) acutely reduces intake of sweet-tasting food due to lower liking. However, little is known about other physiological responses during both the prandial and postprandial phase. Here, we explored the effects of Gymnema sylvestre (GS)-based suppression of OSS of several types of sweet-tasting food (muffin, sweet yogurt, banana) on gastric emptying, blood glucose (BG), plasma insulin (PI), appetite indices (hunger, fullness and prospective consumption), satisfaction and desire for tastes. Fifteen healthy subjects (22 ± 3 years, 9 women) took part in the study. Subjects rinsed their mouth with either GS solution or distilled water before eating the sweet-tasting food. Subjects felt decreased sweet taste intensity and reduced taste liking associated with GS rinsing after consuming each food, compared with rinsing with distilled water (p < 0.05). Gastric emptying, BG, PI and appetite indices during and after the prandial phase did not significantly change with GS rinsing compared to rinsing with distilled water (p > 0.05). Higher desire for sweet taste as well as lower satisfaction (p < 0.05) in the postprandial phase were observed with GS rinsing. These results suggest that the suppression of OSS does not affect gastric emptying, glycemic response and appetite during and after consumption of sweet-tasting food.

Nicotinamide phosphoribosyltransferase is a molecular target of potent anticancer agents identified from phenotype-based drug screening.

Phenotypic screening in drug discovery has been revived with the expectation of providing promising lead compounds and drug targets and improving the success rate of drug approval. However, target identification remains a major bottleneck in phenotype-based drug discovery. We identified the lead compounds K542 and K405 with a selective inhibition of cell viability against sphingosine-1-phosphate lyase 1 (SGPL1)-transduced ES-2 cells by phenotypic screening. We therefore performed an in vivo pharmacological examination and observed the antitumor activity of K542 in an HT-1080 tumor-bearing mouse xenograft model. SGPL1 was expected to be a therapeutic target in some cancers, suggesting that these lead molecules might be promising candidates; however, their mechanisms of action still remain unexplained. We therefore synthesized the affinity probe Ind-tag derived from K542 and identified the proteins binding to Ind-tag via a pull-down experiment. Proteomics and biochemical analyses revealed that the target molecule of these lead compounds was Nicotinamide phosphoribosyltransferase (NAMPT). We established K542-resistant DLD-1 and HT-1080 cells, and genetic analyses of these cells identified a missense mutation in the NAMPT-encoding gene. This enzymatic experiment clearly showed that K393 exerts enzymatic inhibition against NAMPT. These proteomics, genetics and biochemical analyses clarified that compounds K542 and K405 were NAMPT inhibitors.