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Effect of artesunate on insulin resistance in type 1 diabetic mouse through PI3K/GSK-3β pathway
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DOI   10.11656/j.issn.1672-1519.2022.08.23
Key Words   type 1 diabetes;artesunate;insulin resistance;PI3K/GSK3β signaling pathway
Author NameAffiliation
XU Yanling First Department of Endocrinology, Shenyang Fifth People's Hospital, Shenyang 110000, China 
ZHAO Yuzhu First Department of Endocrinology, Shenyang Fifth People's Hospital, Shenyang 110000, China 
FU Yu First Department of Endocrinology, Shenyang Fifth People's Hospital, Shenyang 110000, China 
MU Zhongyi Department of Urology, Liaoning Cancer Hospital, Shenyang 110000, China 
Abstract
    [Objective] To observe the effects of artesunate on insulin resistance in type 1 diabetic mice,and to explore its mechanism of action. [Methods] Balb/c mice were injected intraperitoneally with 200 mg/kg STZ to establish a type 1 diabetic mouse model,and they were randomly divided into model group,artesunate group and insulin group. In addition,10 Balb/c mice were randomly selected as the healthy control group,and the same amount of normal saline was injected intraperitoneally. After successful modeling,the artesunate group was intragastrically administered with 100 mg/kg artesunate,and the healthy control group and model group were intragastrically administered with the same amount of normal saline once a day for 4 weeks,in the insulin group,4 U/kg insulin glargine injection was subcutaneously injected once a day for 5 consecutive days. Fasting blood glucose (FBG),fasting insulin (FINS),insulin resistance index (HOMA-IR),liver triglycerides (TG),malondialdehyde (MDA),and serum free fatty acids (FFA) were detected in each group of mice. HE staining was used to observe the pathology of mouse pancreatic islets. The expression levels of PI3K,p-PI3K,Akt,p-Akt,GSK3β,p- GSK3β and GS protein in each group were detected by Western blot. [Results] Compared with the healthy control group,the content of FBG,FINS,HOMA-IR,TG,MDA and FFA in the model group was increased significantly (P<0.05),the protein ratio of p-PI3K/PI3K and p-Akt/Akt and the expression of GS protein was decreased significantly (P<0.05),the expression ratio of p-GSK3β/GSK3β protein was significantly increased (P<0.05). Compared with the model group,the contents of FBG,FINS,HOMA-IR,TG,MDA and FFA in the artesunate group and the insulin group were significantly reduced (P<0.05),the protein ratio of p-PI3K/PI3K and the expression level of p-Akt/Akt and GS protein were increased significantly (P<0.05),and the ratio of p-GSK3β/GSK3β protein expression level wass decreased significantly (P<0.05). [Conclusion] Artesunate can significantly reduce insulin resistance and glucose content in type 1 diabetic mice. Its mechanism of action maybe related to the inhibition of PI3K/GSK3β signaling pathway.

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