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

The aim was to characterize a phenolic-rich water extract from the pericarp of an improved genotype of Apache red maize (RPE) and evaluate its ability to activate the type 2 diabetes markers free fatty acid receptor 1 (GPR40) and glucokinase (GK) in vitro. The extract contained mainly phenolic acids, anthocyanins, and other flavonoids. RPE inhibited α-amylase (IC₅₀ = 88.3 μg/mL), α-glucosidase (IC₅₀ = 169.3 μg/mL), and reduced glucose transport in a Caco-2 cell monolayer (up to 25%). Furthermore, RPE activated GPR40 (EC₅₀ = 77.7 μg/mL) in pancreatic INS-1E cells and GK (EC₅₀ = 43.4 μg/mL) in liver HepG2 cells, potentially through allosteric modulation. RPE activated GPR40-related insulin secretory pathway and activated the glucose metabolism regulator AMPK (up to 78%). Our results support the hypothesis that foods with a high concentration of anthocyanins and phenolic acids, such as in the selected variety of maize used, could ameliorate obesity and type 2 diabetes comorbidities.