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Intervention of Gastrodin in Type 2 Diabetes Mellitus and Its Mechanism

As a severe metabolic disease, type 2 diabetes mellitus (T2DM) has become a serious threat to human health in recent years. Gastrodin, as a primary chemical constituent in Gastrodia elata Blume, has antidiabetic effects. However, the possible mechanisms are unclear. The aim of the present study was...

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Autores principales: Bai, Yu, Mo, Ke, Wang, Guirong, Chen, Wanling, Zhang, Wei, Guo, Yibo, Sun, Zhirong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481818/
https://www.ncbi.nlm.nih.gov/pubmed/34603025
http://dx.doi.org/10.3389/fphar.2021.710722
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author Bai, Yu
Mo, Ke
Wang, Guirong
Chen, Wanling
Zhang, Wei
Guo, Yibo
Sun, Zhirong
author_facet Bai, Yu
Mo, Ke
Wang, Guirong
Chen, Wanling
Zhang, Wei
Guo, Yibo
Sun, Zhirong
author_sort Bai, Yu
collection PubMed
description As a severe metabolic disease, type 2 diabetes mellitus (T2DM) has become a serious threat to human health in recent years. Gastrodin, as a primary chemical constituent in Gastrodia elata Blume, has antidiabetic effects. However, the possible mechanisms are unclear. The aim of the present study was to investigate the effects and possible mechanisms of gastrodin on the treatment of T2DM. In vivo, after treatment with gastrodin for 6 weeks, fasting blood glucose levels, blood lipid metabolism, and insulin sensitivity index values were remarkably reduced compared with those of the diabetic control group. The values of aspartate aminotransferase and alanine aminotransferase also showed that gastrodin alleviates liver toxicity caused by diabetes. Moreover, gastrodin relieved pathological damage to the pancreas in T2DM rats. In vitro, gastrodin alleviated insulin resistance by increasing glucose consumption, glucose uptake, and glycogen content in dexamethasone-induced HepG2 cells. The Western blotting results showed that gastrodin upregulated the expression of insulin receptors and ubiquitin-specific protease 4 (USP4) and increased the phosphorylation of GATA binding protein 1 (GATA1) and protein kinase B (AKT) in vivo and in vitro. Furthermore, gastrodin decreased the ubiquitin level of the insulin receptor via UPS4 and increased the binding of GATA1 to the USP4 promoter. Additionally, administration of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway inhibitors MK-2206 and LY294002 abolished the beneficial effects of gastrodin. Our results indicate that gastrodin promotes the phosphorylation of GATA1 via the PI3K/AKT pathway, enhances the transcriptional activity of GATA1, and then increases the expression level of USP4, thereby reducing the ubiquitination and degradation of insulin receptors and ultimately improving insulin resistance. Our study provides scientific evidence for the beneficial actions and underlying mechanism of gastrodin in the treatment of T2DM.
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spelling pubmed-84818182021-10-01 Intervention of Gastrodin in Type 2 Diabetes Mellitus and Its Mechanism Bai, Yu Mo, Ke Wang, Guirong Chen, Wanling Zhang, Wei Guo, Yibo Sun, Zhirong Front Pharmacol Pharmacology As a severe metabolic disease, type 2 diabetes mellitus (T2DM) has become a serious threat to human health in recent years. Gastrodin, as a primary chemical constituent in Gastrodia elata Blume, has antidiabetic effects. However, the possible mechanisms are unclear. The aim of the present study was to investigate the effects and possible mechanisms of gastrodin on the treatment of T2DM. In vivo, after treatment with gastrodin for 6 weeks, fasting blood glucose levels, blood lipid metabolism, and insulin sensitivity index values were remarkably reduced compared with those of the diabetic control group. The values of aspartate aminotransferase and alanine aminotransferase also showed that gastrodin alleviates liver toxicity caused by diabetes. Moreover, gastrodin relieved pathological damage to the pancreas in T2DM rats. In vitro, gastrodin alleviated insulin resistance by increasing glucose consumption, glucose uptake, and glycogen content in dexamethasone-induced HepG2 cells. The Western blotting results showed that gastrodin upregulated the expression of insulin receptors and ubiquitin-specific protease 4 (USP4) and increased the phosphorylation of GATA binding protein 1 (GATA1) and protein kinase B (AKT) in vivo and in vitro. Furthermore, gastrodin decreased the ubiquitin level of the insulin receptor via UPS4 and increased the binding of GATA1 to the USP4 promoter. Additionally, administration of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway inhibitors MK-2206 and LY294002 abolished the beneficial effects of gastrodin. Our results indicate that gastrodin promotes the phosphorylation of GATA1 via the PI3K/AKT pathway, enhances the transcriptional activity of GATA1, and then increases the expression level of USP4, thereby reducing the ubiquitination and degradation of insulin receptors and ultimately improving insulin resistance. Our study provides scientific evidence for the beneficial actions and underlying mechanism of gastrodin in the treatment of T2DM. Frontiers Media S.A. 2021-09-16 /pmc/articles/PMC8481818/ /pubmed/34603025 http://dx.doi.org/10.3389/fphar.2021.710722 Text en Copyright © 2021 Bai, Mo, Wang, Chen, Zhang, Guo and Sun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Bai, Yu
Mo, Ke
Wang, Guirong
Chen, Wanling
Zhang, Wei
Guo, Yibo
Sun, Zhirong
Intervention of Gastrodin in Type 2 Diabetes Mellitus and Its Mechanism
title Intervention of Gastrodin in Type 2 Diabetes Mellitus and Its Mechanism
title_full Intervention of Gastrodin in Type 2 Diabetes Mellitus and Its Mechanism
title_fullStr Intervention of Gastrodin in Type 2 Diabetes Mellitus and Its Mechanism
title_full_unstemmed Intervention of Gastrodin in Type 2 Diabetes Mellitus and Its Mechanism
title_short Intervention of Gastrodin in Type 2 Diabetes Mellitus and Its Mechanism
title_sort intervention of gastrodin in type 2 diabetes mellitus and its mechanism
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481818/
https://www.ncbi.nlm.nih.gov/pubmed/34603025
http://dx.doi.org/10.3389/fphar.2021.710722
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