Inhibition of Glucose Transport by Tomatoside A, a Tomato Seed Steroidal Saponin, through the Suppression of GLUT2 Expression in Caco-2 Cells

Abstract

We investigated whether tomatoside A (5α-furostane-3β,22,26-triol-3-[O-β-d-glucopyranosyl (1→2)-β-d-glucopyranosyl (1→4)-β-d-galactopyranoside] 26-O-β-d-glucopyranoside), a tomato seed saponin, may play a role in the regulation of intestinal glucose transport in human intestinal Caco-2 cells. Tomatoside A could not penetrate through Caco-2 cell monolayers, as observed in the transport experiments using liquid chromatography-mass spectrometry. The treatment of cells with 10 μM tomatoside A for 3 h resulted in a 46.0% reduction in glucose transport as compared to untreated cells. Western blotting analyses revealed that tomatoside A significantly (p < 0.05) suppressed the expression of glucose transporter 2 (GLUT2) in Caco-2 cells, while no change in the expression of sodium-dependent glucose transporter 1 was observed. In glucose transport experiments, the reduced glucose transport by tomatoside A was ameliorated by a protein kinase C (PKC) inhibitor and a multidrug resistance-associated protein 2 (MRP2) inhibitor. The tomatoside A-induced reduction in glucose transport was restored in cells treated with apical sodium-dependent bile acid transporter (ASBT) siRNA or an ASBT antagonist. These findings demonstrated for the first time that the nontransportable tomato seed steroidal saponin, tomatoside A, suppressed GLUT2 expression via PKC signaling pathway during the ASBT-influx/MRP2-efflux process in Caco-2 cells.

In Vitro Bioaccessibility of Extractable Compounds from Tannat Grape Skin Possessing Health Promoting Properties with Potential to Reduce the Risk of Diabetes

“…The reduction of their formation may be helpful for reducing the risk of diabetes. In addition, the modulation of glucose metabolism by inhibition of carbohydrases activity and glucose transporters is effective for a good control of blood glucose levels [6]. Therefore, natural sources of bioactive compounds able to regulate glucose metabolism and possessing antioxidant and anti-inflammatory properties are of great interest for reducing the risk and treating diabetes.…”

Activating Effects of Phenolics from Apache Red Zea mays L. on Free Fatty Acid Receptor 1 and Glucokinase Evaluated with a Dual Culture System with Epithelial, Pancreatic, and Liver Cells

“…Glucose is transported through the intestine by the glucose transporter 2 (GLUT2) and the sodium−glucose transport protein co-transporters (SGLTs). 30 Some components from food sources have demonstrated the capacity to inhibit GLUT2 and SGLT, 31 and particularly polyphenols have shown potential to decrease monosaccharide absorption by blocking the transporters or modulating their expression. 32 Free fatty acids are some of the most efficient gut hormone secretagogues, presumably through the G-protein-coupled receptors (GPR40 included).…”

Using Caffeine and Free Amino Acids To Enhance the Transepithelial Transport of Catechins in Caco-2 Cells

“…Transepithelial transports for each of EGCG, ECG, and EC with or without caffeine, theanine, serine, or glycine were measured at the final concentration, as indicated above in the transport buffer (HBSS containing 25 mM HEPES at pH 6.0). Considering that catechins are readily oxidized and unstable under neutral or marginally alkaline conditions, the HBSS solution was prepared at pH 6.0 and not pH 7.4 according to previous reports. , Besides, to detect these compounds by ultra-performance liquid chromatography (UPLC), the concentration of the compounds was chosen based on our previous study . The transport buffer was prewarmed at 37 °C and was used for the transport experiments.…”

“…Considering that catechins are readily oxidized and unstable under neutral or marginally alkaline conditions, the HBSS solution was prepared at pH 6.0 and not pH 7.4 according to previous reports. 28,29 Besides, to detect these compounds by ultra-performance liquid chromatography (UPLC), the concentration of the compounds was chosen based on our previous study. 25 The transport buffer was prewarmed at 37 °C and was used for the transport experiments.…”