Anthocyanins from purple corn activate free fatty acid-receptor 1 and glucokinase enhancing in vitro insulin secretion and hepatic glucose uptake

The objective of this study was to evaluate the ability of anthocyanins (ANC) present in purple corn to enhance insulin secretion and hepatic glucose uptake in pancreatic cells and hepatocytes, through activation of the free fatty acid receptor-1 (FFAR1) and glucokinase (GK), respectively. Using a dual-layer cell culture with Caco-2 cells, INS-1E or HepG2 cells were treated with an anthocyanin-rich extract from the pericarp of purple corn (PCW), as well as pure ANC cyanidin-3-O-glucoside (C3G), peonidin-3-O-glucoside, pelargonidin-3O-glucoside. Delphinidin-3-O-glucoside (D3G) was used for comparative purposes. Semi-purified C3G (C3G-P) and condensed forms (CF-P) isolated from PCW were also used. At 100 μM, the pure ANC enhanced glucose-stimulated insulin secretion (GSIS) in INS-1E cells ranging from 18% to 40% (p<0.05) compared to untreated cells. PCW increased GSIS by 51%. D3G was the most effective anthocyanin activating FFAR1 (EC₅₀: 196.6 μM). PCW had activating potential on FFAR1 (EC50: 77 μg/mL). PCW, as well as C3G and D3G increased the expression of FFAR1, PLC, and phosphorylation of PKD, related to the FFAR1-dependent insulin secretory pathway. The treatment with 100 μM of P3G and C3G increased (p<0.05) glucose uptake in HepG2 cells by 19% and 31%. PCW increased the glucose uptake in HepG2 cells by 48%. It was determined that CF-P was the most effective for activating GK (EC₅₀: 39.9 μM) and the PCW extracts had an efficacy of EC₅₀: 44 μg/mL. The ANC in purple corn also reduced AMPK phosphorylation and PEPCK expression in HepG2 cells, known to be related to reduction in gluconeogenesis. It is demonstrated for the first time that dietary ANC can enhance the activity of novel biomarkers FFAR1 and GK and potentially ameliorate type-2 diabetes comorbidities.