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

Abstract

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-3-O-glucoside. Delphinidin-3-O-glucoside (D3G) was used for comparative purposes. Semipurified 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.

Impact of Cyanidin-3-Glucoside on Gut Microbiota and Relationship with Metabolism and Inflammation in High Fat-High Sucrose Diet-Induced Insulin Resistant Mice

“…Previous studies demonstrated that C3G increased the translocation of glucose transporter-4 in skeletal muscle through the activation of insulin and the AMP-activated protein kinase pathway in mice [ 20 ]. C3G also augmented glucose-induced insulin secretion in INS-1E pancreatic β-cells and glucose uptake in HepG2 hepatocytes [ 21 ]. C3G inhibited high-glucose-induced cholesterol accumulation in HK-2 kidney epithelial cells through the activation of the LXRα pathway [ 22 ].…”

A Selective Role of Dietary Anthocyanins and Flavan-3-ols in Reducing the Risk of Type 2 Diabetes Mellitus: A Review of Recent Evidence

“…Anthocyanins may also reduce absorption of glucose through glucose transporter 2 (GLUT2) and the sodium-glucose linked transporter 1 (SGLT1) as suggested by some studies [65,66,67]. They have also been reported to stimulate insulin secretion through activation of l-type voltage-dependent Ca 2+ channels [68] and by the activation of the free fatty acid receptor-1 [69].…”

Influence of Saskatoon Berry and Cyanidin-3-Glucoside on Gut Microbiota and Relationship with Metabolism and Inflammation in High Fat-High Sucrose Diet-Induced Insulin Resistant Mice

“…Previous studies demonstrated that C3G increased the translocation of glucose transporter-4 in skeletal muscle through the activation of insulin and AMP protein kinase pathway in mice [20]. C3G also augmented glucose-induced insulin secretion in INS-1E pancreatic β-cells and glucose uptake in HepG2 hepatocytes [21]. C3G inhibited high glucose-induced cholesterol accumulation in HK-2 kidney epithelial cells through the activation of LXRα pathway [22].…”