Theaflavins inhibit glucose transport across Caco-2 cells through the downregulation of the Ca²⁺/AMP-activated protein kinase-mediated glucose transporter SGLT1

The study investigated the effects of theaflavins, which are intestinally non-absorbable compounds, on intestinal glucose transport in Caco-2 cells. ¹³C₆-Glucose transport experiments clearly revealed that glucose transport across Caco-2 cells was significantly (p < 0.01) inhibited by theaflavins. When Caco-2 cells were treated with 40 μM theaflavins for 24 h, the expression of SGLT1 expression was significantly (p < 0.05) suppressed, whereas no difference in GLUT2 expression was observed. The theaflavin-induced inhibition of glucose transport was reversed by the inhibition of influx routes mediated by OATP and MCT transporters. A Wes analysis established that theaflavin-induced phosphorylation of AMPK was significantly (p < 0.05) suppressed by the inhibition of endoplasmic reticulum Ca²⁺-release and CaMKK β. These findings demonstrated for the first time that theaflavins can inhibit glucose transport across Caco-2 cell monolayers through the suppression of SGLT1 expression partly via the activation of the intracellular Ca²⁺/CaMKK β/AMPK signaling pathway.