Selective detoxification of digesta revealed how cold-pressed apple fractions modulate transepithelial glucose transport and stimulate GLP-1 secretion

This study examined whether whole apple and apple pomace modulate transepithelial glucose transport and GLP-1 secretion under physiologically relevant in vitro conditions, achieved via a laboratory-implementable solubilization and purification method that doubled polyphenol concentrations without inducing cytotoxicity. Samples collected at the end of the gastric and intestinal phases represented pre- and post-intestinal chyme. Purified digesta were incubated with Caco-2 monolayers, and UHPLC-ESI-QTOF-MS/MS analysis of 48 polyphenols across apical, intracellular, and basolateral compartments showed predominant apical retention. Apple and pomace inhibited glucose transport, primarily driven by dihydrochalcones and hydroxybenzoic acids (Spearman ρ > 0.70). Notably, although phloridzin alone inhibited GLP-1 secretion in mouse STC-1 L-cells, gastric digesta of both apple and pomace enhanced secretion by 50%. However, pomace digesta retained this effect after intestinal digestion, increasing GLP-1 by 179% and 62% compared to the glucose and intestinal blank controls, respectively. These findings suggest that pomace intake may attenuate postprandial glycemia and regulate appetite. • A lab-implementable digestate clean-up method was developed for cell-based assays • Pomace, and specially apple digestates, inhibited transepithelial glucose transport • Glucose transport inhibition was driven by DHCs and HBAs (Spearman ρ > 0.70) • Gastric digestates from apple and pomace significantly enhanced GLP-1 secretion • Pomace, but not apple, intestinal digestates significantly enhanced GLP-1 secretion