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Mechanism of stilbene compounds on the improvement of insulin resistance by IRS-1/PI3K/AKT/GLUT4 pathway
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DOI   10.11656/j.issn.1673-9043.2023.01.18
Key Words   stilbene;adipocyte;insulin resistance;IRS-1/PI3K/AKT/GLUT4
Author NameAffiliationE-mail
XU Yifang School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
LI Zhipeng School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
CAO Shijie State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
KANG Ning School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China kangndd@163.com 
Abstract
    [Objective] The aim of this study is to investigate the mechanism of three traditional Chinese medicines (Polygoni Cuspidati Rhizoma et Radix,Mori Cortex,Polygoni Multiflori Radix) derived stilbene compounds in improving insulin resistance.[Methods] The insulin resistance model was established by using tumor necrosis factor α (TNF-α) for 96 h in 3T3-L1 adipocytes. Thiazolyl blue tetrazolium bromide (MTT) method was used to detect the survival rates of adipocytes with stilbene compounds,such as resveratrol (RES),polydatin (PD),mulberroside A (Mul A) and 2,3,5,4'-tetrahydroxyl diphenylethylene-2-O-glucoside (THSG). Glucose content in supernatant of cell culture medium was detected by glucose kit. Protein expression levels of insulin receptor substrate-1 (IRS-1),p-IRS-1,phosphatidylinositol3-kinase (PI3K),p-PI3K,protein kinase B (AKT),p-AKT, glucose transporter 4 (GLUT4) were detected by Western Blot,and the mRNA expression of GLUT4 was detected by RT-PCR.[Results] Compared with those in the normal group,the glucose consumption rate of the model group was significantly down-regulated,meanwhile the protein expression of p-IRS-1 (Ser307) was significantly increased,the expressions of p-PI3K and p-AKT (Ser473) and GLUT4 were down-decreased,and the mRNA expression of GLUT4 was significantly decreased. Compared with the model group,RES,Mul A,and THSG could significantly increase the glucose consumption,while PD has no such effect. Moreover,the protein expressions of p-IRS-1 (Ser307) and p-PI3K and p-AKT (Ser473) and GLUT4 were significantly reversed by Mul A and THSG. However,RES only significantly reverse the protein expressions of p-IRS-1 (Ser307) and GLUT4. THSG could significantly increase the mRNA expression of GLUT4.[Conclusion] Mul A and THSG could improve the insulin resistance via IRS-1/PI3K/AKT/GLUT4 signaling pathway in the adipocytes. RES could improve the insulin resistance by activating IRS-1 and GLUT4 but not through the PI3K/AKT pathway in the adipocytes,and PD has no hypoglycemic activity.

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