Anti-diabetic effect of anthocyanin cyanidin-3-O-glucoside: data from insulin resistant hepatocyte and diabetic mouse

Abstract Background Anthocyanins are a group of natural products widely found in plants. They have been found to alleviate the disorders of glucose metabolism in type 2 diabetes mellitus (T2DM), while the underlying mechanisms remain unclear. Methods HepG2 and L02 cells were incubated with 0.2 mM PA...

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Main Authors: Xiang Ye, Wen Chen, Xu-Fan Huang, Fu-Jie Yan, Shui-Guang Deng, Xiao-Dong Zheng, Peng-Fei Shan
Format: Article
Language:English
Published: Nature Publishing Group 2024-03-01
Series:Nutrition & Diabetes
Online Access:https://doi.org/10.1038/s41387-024-00265-7
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author Xiang Ye
Wen Chen
Xu-Fan Huang
Fu-Jie Yan
Shui-Guang Deng
Xiao-Dong Zheng
Peng-Fei Shan
author_facet Xiang Ye
Wen Chen
Xu-Fan Huang
Fu-Jie Yan
Shui-Guang Deng
Xiao-Dong Zheng
Peng-Fei Shan
author_sort Xiang Ye
collection DOAJ
description Abstract Background Anthocyanins are a group of natural products widely found in plants. They have been found to alleviate the disorders of glucose metabolism in type 2 diabetes mellitus (T2DM), while the underlying mechanisms remain unclear. Methods HepG2 and L02 cells were incubated with 0.2 mM PA and 30 mM glucose for 24 h to induce IR, and cells treated with 5 mM glucose were used as the control. C57BL/6 J male mice and db/db male mice were fed with a chow diet and gavaged with pure water or cyanidin-3-O-glucoside (C3G) solution (150 mg/kg/day) for 6 weeks. Results In this study, the anthocyanin C3G, extracted from red bayberry, was found to alleviate disorders of glucose metabolism, which resulted in increased insulin sensitivity in hepatocytes, and achieved by enhancing the glucose consumption as well as glycogen synthesis in insulin resistance (IR) hepatpcytes. Subsequently, the expression of key proteins involved in IR was detected by western blotting analysis. Protein tyrosine phosphatase-1B (PTP1B), a negative regulator of insulin signaling, could reduce cellular sensitivity to insulin by inhibiting the phosphorylation of insulin receptor substrate-2 (IRS-2). Results of this study showed that C3G inhibited the increase in PTP1B after high glucose and palmitic acid treatment. And this inhibition was accompanied by increased phosphorylation of IRS proteins. Furthermore, the effect of C3G on improving IR in vivo was validated by using a diabetic db/db mouse model. Conclusion These findings demonstrated that C3G could alleviate IR in vitro and in vivo to increase insulin sensitivity, which may offer a new insight for regulating glucose metabolism during T2DM by using the natural dietary bioactive components. C3G promotes the phosphorylation of IRS-2 proteins by suppressing the expression of PTP1B, and then enhances the sensitivity of hepatocyte to insulin.
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spelling doaj.art-6793ed404e4049c79d491fb7db2df7352024-03-05T20:46:22ZengNature Publishing GroupNutrition & Diabetes2044-40522024-03-011411810.1038/s41387-024-00265-7Anti-diabetic effect of anthocyanin cyanidin-3-O-glucoside: data from insulin resistant hepatocyte and diabetic mouseXiang Ye0Wen Chen1Xu-Fan Huang2Fu-Jie Yan3Shui-Guang Deng4Xiao-Dong Zheng5Peng-Fei Shan6Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Zhejiang University School of MedicineCollege of Biosystems Engineering and Food Science, Zhejiang UniversityDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital of Zhejiang University School of MedicineCollege of Biosystems Engineering and Food Science, Zhejiang UniversityAdvanced Computing and System Laboratory, College of Computer Science and Technology, Zhejiang UniversityCollege of Biosystems Engineering and Food Science, Zhejiang UniversityDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital of Zhejiang University School of MedicineAbstract Background Anthocyanins are a group of natural products widely found in plants. They have been found to alleviate the disorders of glucose metabolism in type 2 diabetes mellitus (T2DM), while the underlying mechanisms remain unclear. Methods HepG2 and L02 cells were incubated with 0.2 mM PA and 30 mM glucose for 24 h to induce IR, and cells treated with 5 mM glucose were used as the control. C57BL/6 J male mice and db/db male mice were fed with a chow diet and gavaged with pure water or cyanidin-3-O-glucoside (C3G) solution (150 mg/kg/day) for 6 weeks. Results In this study, the anthocyanin C3G, extracted from red bayberry, was found to alleviate disorders of glucose metabolism, which resulted in increased insulin sensitivity in hepatocytes, and achieved by enhancing the glucose consumption as well as glycogen synthesis in insulin resistance (IR) hepatpcytes. Subsequently, the expression of key proteins involved in IR was detected by western blotting analysis. Protein tyrosine phosphatase-1B (PTP1B), a negative regulator of insulin signaling, could reduce cellular sensitivity to insulin by inhibiting the phosphorylation of insulin receptor substrate-2 (IRS-2). Results of this study showed that C3G inhibited the increase in PTP1B after high glucose and palmitic acid treatment. And this inhibition was accompanied by increased phosphorylation of IRS proteins. Furthermore, the effect of C3G on improving IR in vivo was validated by using a diabetic db/db mouse model. Conclusion These findings demonstrated that C3G could alleviate IR in vitro and in vivo to increase insulin sensitivity, which may offer a new insight for regulating glucose metabolism during T2DM by using the natural dietary bioactive components. C3G promotes the phosphorylation of IRS-2 proteins by suppressing the expression of PTP1B, and then enhances the sensitivity of hepatocyte to insulin.https://doi.org/10.1038/s41387-024-00265-7
spellingShingle Xiang Ye
Wen Chen
Xu-Fan Huang
Fu-Jie Yan
Shui-Guang Deng
Xiao-Dong Zheng
Peng-Fei Shan
Anti-diabetic effect of anthocyanin cyanidin-3-O-glucoside: data from insulin resistant hepatocyte and diabetic mouse
Nutrition & Diabetes
title Anti-diabetic effect of anthocyanin cyanidin-3-O-glucoside: data from insulin resistant hepatocyte and diabetic mouse
title_full Anti-diabetic effect of anthocyanin cyanidin-3-O-glucoside: data from insulin resistant hepatocyte and diabetic mouse
title_fullStr Anti-diabetic effect of anthocyanin cyanidin-3-O-glucoside: data from insulin resistant hepatocyte and diabetic mouse
title_full_unstemmed Anti-diabetic effect of anthocyanin cyanidin-3-O-glucoside: data from insulin resistant hepatocyte and diabetic mouse
title_short Anti-diabetic effect of anthocyanin cyanidin-3-O-glucoside: data from insulin resistant hepatocyte and diabetic mouse
title_sort anti diabetic effect of anthocyanin cyanidin 3 o glucoside data from insulin resistant hepatocyte and diabetic mouse
url https://doi.org/10.1038/s41387-024-00265-7
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