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Hirsutine ameliorates hepatic and cardiac insulin resistance in high-fat diet-induced diabetic mice and in vitro models
Hu, Wei1; Li, Meng1; Sun, Wuyi2; Li, Qixiu3; Xi, Haiyan3; Qiu, Yuanye1; Wang, Ran1; Ding, Qian1; Wang, Zhou1; Yu, Yue1; Lei, Heping4; Mao, Yicheng3; Zhu, Yi Zhun1,3
2022-03-01
Source PublicationPharmacological Research
ISSN1043-6618
Volume177
Abstract

Closely associated with type 2 diabetes mellitus (T2DM), hepatic steatosis and cardiac hypertrophy resulting from chronic excess intake can exacerbate insulin resistance (IR). The current study aims to investigate the pharmacological effects of hirsutine, one indole alkaloid isolated from Uncaria rhynchophylla, on improving hepatic and cardiac IR, and elucidate the underlying mechanism. T2DM and IR in vivo were established by high-fat diet (HFD) feeding for 3 months in C57BL/6 J mice. In vitro IR models were induced by high-glucose and high-insulin (HGHI) incubation in HepG2 and H9c2 cells. Hirsutine administration for 8 weeks improved HFD-induced peripheral hyperglycemia, glucose tolerance and IR by OGTT and ITT assays, and simultaneously attenuated hepatic steatosis and cardiac hypertrophy by pathological observation. The impaired p-Akt expression was activated by hirsutine in liver and heart tissues of HFD mice, and also in the models in vitro. Hirsutine exhibited the effects on enhancing glucose consumption and uptake in IR cell models via activating phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which was blocked by PI3K inhibitor LY294002. Moreover, the effect of hirsutine on promoting glucose uptake and GLUT4 expression in HGHI H9c2 cells was also prevented by Compound C, an inhibitor of AMP-activated protein kinase (AMPK). Enhancement of glycolysis might be another factor of hirsutine showing its effects on glycemic control. Collectively, it was uncovered that hirsutine might exert beneficial effects on regulating glucose homeostasis, thus improving hepatic and cardiac IR, and could be a promising compound for treating diet-induced T2DM.

KeywordGlucose Metabolism Hfd Hirsutine Insulin Resistance Pi3k/akt Signaling T2dm
DOI10.1016/j.phrs.2021.105917
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000788113100005
Scopus ID2-s2.0-85122304685
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorMao, Yicheng; Zhu, Yi Zhun
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Macau, China
2.Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China
3.Shanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai, China
4.Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, China
First Author AffilicationUniversity of Macau
Corresponding Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Hu, Wei,Li, Meng,Sun, Wuyi,et al. Hirsutine ameliorates hepatic and cardiac insulin resistance in high-fat diet-induced diabetic mice and in vitro models[J]. Pharmacological Research,2022,177.
APA Hu, Wei,Li, Meng,Sun, Wuyi,Li, Qixiu,Xi, Haiyan,Qiu, Yuanye,Wang, Ran,Ding, Qian,Wang, Zhou,Yu, Yue,Lei, Heping,Mao, Yicheng,&Zhu, Yi Zhun.(2022).Hirsutine ameliorates hepatic and cardiac insulin resistance in high-fat diet-induced diabetic mice and in vitro models.Pharmacological Research,177.
MLA Hu, Wei,et al."Hirsutine ameliorates hepatic and cardiac insulin resistance in high-fat diet-induced diabetic mice and in vitro models".Pharmacological Research 177(2022).
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