PMID- 34841692 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20220401 IS - 1613-4133 (Electronic) IS - 1613-4125 (Linking) VI - 66 IP - 2 DP - 2022 Jan TI - Cyanidin-3-O-Glucoside Supplementation Ameliorates Metabolic Insulin Resistance via Restoration of Nitric Oxide-Mediated Endothelial Insulin Transport. PG - e2100742 LID - 10.1002/mnfr.202100742 [doi] AB - SCOPE: Anthocyanin cyanidin-3-O-glucoside (Cy3G) possesses 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 can modulate metabolic insulin resistance via regulating endothelial insulin transport is not reported yet. METHODS AND RESULTS: Palmitic acid (PA)-treated mouse aortic endothelial cells (MAECs) model and high-fat diet (HFD) fed mice model are used. Compared with HFD mice, Cy3G supplementation decrease exogenous insulin content in skeletal muscle and ameliorate metabolic insulin resistance. In culture, Cy3G can directly ameliorate PA-induced impairment on FITC-insulin uptake in MAECs. Mechanistically, Cy3G can effectively decrease inflammatory cytokines and toll-like receptor 4 (TLR4)/nuclear factor-kappa-B inhibitor alpha (IkappaBalpha) activation, and restore the attenuated Akt/eNOS signaling pathway. Blunted nitric oxide (NO) synthase with N-nitro-l-arginine methyl ester (L-NAME) can 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 can directly restore the attenuated nitic oxide-mediated endothelial insulin transport and thereby ameliorate metabolic insulin resistance. Our finding can provide a novel explanation for the anti-diabetic effects of Cy3G. CI - (c) 2021 Wiley-VCH GmbH. FAU - Geng, Xiuwen AU - Geng X AD - Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, 510080, P.R. China. AD - Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province, 510080, P.R. China. FAU - Ji, Jiajun AU - Ji J AD - Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, 510080, P.R. China. AD - Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province, 510080, P.R. China. FAU - Liu, Yuanhua AU - Liu Y AD - Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, 510080, P.R. China. AD - Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province, 510080, P.R. China. FAU - Li, Xueyan AU - Li X AD - Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, 510080, P.R. China. AD - Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province, 510080, P.R. China. FAU - Chen, Yunan AU - Chen Y AD - Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, 510080, P.R. China. AD - Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province, 510080, P.R. China. FAU - Su, Lei AU - Su L AD - Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, 510080, P.R. China. AD - Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province, 510080, P.R. China. FAU - Zhao, Lina AU - Zhao L AUID- ORCID: 0000-0002-4258-6404 AD - Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, 510080, P.R. China. AD - Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province, 510080, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211211 PL - Germany TA - Mol Nutr Food Res JT - Molecular nutrition & food research JID - 101231818 RN - 0 (Anthocyanins) RN - 0 (Glucosides) RN - 0 (Insulin) RN - 31C4KY9ESH (Nitric Oxide) RN - 7732ZHU564 (cyanidin) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) SB - IM MH - Animals MH - Anthocyanins/metabolism/pharmacology MH - Dietary Supplements MH - Endothelial Cells MH - Glucosides/metabolism/pharmacology MH - Insulin/metabolism MH - *Insulin Resistance MH - Mice MH - Nitric Oxide/metabolism MH - Nitric Oxide Synthase Type III/metabolism OTO - NOTNLM OT - cyanidin-3-O-glucoside OT - endothelial cells OT - insulin resistance OT - insulin transport OT - nitric oxide EDAT- 2021/11/30 06:00 MHDA- 2022/04/01 06:00 CRDT- 2021/11/29 06:55 PHST- 2021/10/18 00:00 [revised] PHST- 2021/08/06 00:00 [received] PHST- 2021/11/30 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2021/11/29 06:55 [entrez] AID - 10.1002/mnfr.202100742 [doi] PST - ppublish SO - Mol Nutr Food Res. 2022 Jan;66(2):e2100742. doi: 10.1002/mnfr.202100742. Epub 2021 Dec 11.