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.
Highlights
Diabetes is a complex metabolic disease that affects more than 30 million people in the United States (U.S.) and it has been estimated that this number will become approximately 48.3 million in 2050 [1, 2]
Regarding CF-P, the MS2 spectra showed two main fragments with an m/z of 737.2 and 899.2 (Fig 1F). This fragmentation pattern concurs with that found in colored corn by Gonzalez-Manzano et al, [41] for catechin-(4,8)-cyanidin3,5-diglucoside
We report that ANC in purple corn increase insulin secretion in pancreatic β-cells in vitro potentially through activation of free fatty acid receptor-1 (FFAR1)
Summary
Diabetes is a complex metabolic disease that affects more than 30 million people in the United States (U.S.) and it has been estimated that this number will become approximately 48.3 million in 2050 [1, 2]. The inability to control blood glucose increases the risk of severe health. Anthocyanins from purple corn activate FFAR1 and GK in vitro complications and diabetes remains as a leading cause of death in the U.S [2]. The exact etiology for this condition is unclear, epidemiologic studies have shown that older age, poor dietary habits, physical inactivity and excess body weight are some of the main risk factors [4,5,6]. Dietary intervention strategies have been shown to be beneficial to control hyperglycemia, especially the intake of whole grains, fruits, vegetables, nuts and legumes [7]. The increased consumption of polyphenols, such as anthocyanins (ANC), has been correlated with a lower incidence of type-2 diabetes in humans [8,9,10]
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