Cyanidin-3-O-glucoside supplementation ameliorates metabolic insulin resistance via restoration of nitric oxide-mediated endothelial insulin transport

Mol Nutr Food Res. 2021 Nov 28:e2100742. doi: 10.1002/mnfr.202100742. Online ahead of print.

ABSTRACT

SCOPE: Anthocyanin cyanidin-3-O-glucoside (Cy3G) has a great potential in prevention of diabetes and its vascular complications while the underlying mechanisms are still far from clear. Accumulating evidence suggests that endothelial insulin transport plays a critical role in regulating metabolic insulin sensitivity. Whether Cy3G could modulate metabolic insulin resistance via regulating endothelial insulin transport has not been reported yet.

METHODS AND RESULTS: Palmitic acid (PA)-treated mouse aortic endothelial cells (MAECs) model and high-fat diet (HFD) fed mice model were used. Compared with HFD mice, Cy3G supplementation decrease exogenous insulin content in skeletal muscle and ameliorate metabolic insulin resistance. In culture, Cy3G could directly ameliorate PA-induced impairment on FITC-insulin uptake in MAECs. Mechanistically, Cy3G could effectively decrease inflammatory cytokines and toll-like receptor 4 (TLR4)/ nuclear factor-kappa-B inhibitor alpha (IκBα) activation, and restore the attenuated Akt/eNOS signaling pathway. Blunted nitric oxide synthase with N-nitro-L-arginine methyl ester (L-NAME) could effectively abolish the protective role of Cy3G on endothelial insulin transport and insulin-stimulated glucose utilization in HFD-fed mice.

CONCLUSIONS: These findings suggest that Cy3G supplementation could directly restore the attenuated nitic oxide-mediated endothelial insulin transport and thereby ameliorate metabolic insulin resistance. Our finding might provide a novel explanation for the anti-diabetic effects of Cy3G. This article is protected by copyright. All rights reserved.

PMID:34841692 | DOI:10.1002/mnfr.202100742