Abstract：Objective To clarify the effect of astragalus polysaccharide （AP） on insulin resistance model of HepG2 cells induced by hyperinsulinemia and its underlying molecular mechanism in lipid metabolism and oxidative stress. Methods HepG2 cells were divided into three groups： the control group was treated without any intervention; the model group was treated with 200 μL cell culture medium containing 10-6 mol/L insulin for 48 hours to build an insulin resistance model; the AP group was treated with optimal concentration of AP based on an insulin resistance model. After 24 hours, the concentration of H2O2 and the expression of PPARγ in each group were detected. Results AP could improve the survival rate of insulin-resistant HepG2 cells in a dose-dependent manner. The highest survival rate of the cells was （118.26±1.17）% with 10 μM AP. The concentration of H2O2 in the AP group was （0.82±0.09） μM, which was lower than （1.30±0.16） μM in the model group （P<0.05）, but was close to （0.78±0.09） μM in the control group （P>0.05）. The relative mRNA expression of PPARγ in the AP group was 0.96±0.04, which was higher than 0.51±0.05 in the model group （P<0.05）, but was close to 1.00±0.11 in the control group （P>0.05）. Conclusions In the insulin resistance model in vitro, AP can significantly increase the cell survival rate, reduce intracellular H2O2 concentration, and promote the expression of PPARγ. The mechanism may be related to lipid metabolism.
[1] GUARIGUATA L.Contribute data to the 6th edition of the IDF Diabetes Atlas[J]. Diabetes Res Clin Pract,2013,100(2):280-281. [2] WU H B,ZHONG J M,HU R Y,et al.Rapidly rising incidence of type 1 diabetes in children and adolescents aged 0-19 years in Zhejiang,China,2007 to 2013[J]. Diabet Med,2016,33(10):1339-1346. [3] 朱元斌,许向东,潘杰. 南浔区50岁及以上人群2型糖尿病患病率调查[J]. 预防医学,2018,30(11):1138-1141. [4] XU Y,WANG L M,HE J,et al.Prevalence and control of diabetes in Chinese adults[J]. JAMA,2013,310(9):948-958. [5] LI Y,DING L,HASSAN W,et al.Adipokines and hepatic insulin resistance[J]. J Diabetes Res,2013(2):170532. [6] SALTIEL A R,KAHN C R.Insulin signaling and the regulation of glucose and lipid metabolism[J]. Nature,2011,414(6865):799-806. [7] KENDALL D M,CUDDIHY R M,BERGENSTAL R M.Clinical application of incretin-based therapy:therapeutic potential,patient selection and clinical use[J]. Am J Med,2009,122(Suppl.6):37-50. [8] BHUVANESWARI S,ANURADHA C V.Astaxanthin prevents loss of insulin signaling and improves glucose metabolism in liver of insulin resistant mice[J]. Can J Phsiol Pharmacol,2012,90(11):1544-1552. [9] 吴发宝,陈希元.黄芪药理作用研究综述[J]. 中药材,2004, 27(3):232-234. [10] HE X,SHU J,XU L,et al.Inhibitory effect of Astragalus polysaccharides on lipopolysaccharide-induced TNF-α and IL-1β production in THP-1 cells[J]. Molecules,2012,17(3):3155-3164. [11] YEH T S,CHUANG H L,HUANG W C,et al.Astragalus membranaceus improves exercise performance and ameliorates exercise induced fatigue in trained mice[J]. Molecules,2014,19(3):2793-2807. [12] 白崇智,仲启明,武玉鹏,等. 黄芪等5种中药对小鼠辐射损伤防护作用的实验研究[J]. 细胞与分子免疫学杂志,2013,29(10):1052-1054. [13] HU F,LI X,ZHAO L,et al.Antidiabetic properties of purified polysaccharide from Hedysarum polybotrys[J]. Can J Physiol Pharmacol,2010,88(1):64-72. [14] LIU M,WU K,MAO X,et al.Astragalus polysaccharide improves insulin sensitivity in KKAy mice:regulation of PKB/GLUT4 signaling in skeletal muscle[J]. J Ethnopharmacol,2010,127(1):32-37. [15] BOUWENS L,ROOMAN I.Regulation of pancreatic bate-cell mass[J]. Physiol Rev,2005,85(4):1255-1270. [16] EVANS J L,GOLDFINE I D,MADDUX B A,et al.Oxidative stress and stress-activated signaling pathways:a unifying hypothesis of type 2 diabetes[J]. Endocr Rev,2002,23(5):599-622. [17] FAZAKERLEY D J,MINARD A Y,KRYCER J R,et al.Mitochondrial oxidative stress causes insulin resistance without disrupting oxidative phosphorylation[J]. J Biol Chem,2018,293(19):7315-7328. [18] SAKURABA H,MIZUKAMI H,YAGIHASHI N,et al.Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese type Ⅱ diabetic patients[J]. Diabetologia,2002,45(1):85-96. [19] BALAKUMAR P,MAHADEVAN N,SAMBATHKUMAR R.A contemporary overview of PPARα/γ dual agonists for the management of diabetic dyslipidemia[J]. Curr Mol Pharmacol,2019,12(3): 195-201. [20] LAN D Y,SHEN X D,YUAN W W,et al.Sumoylation of PPARγ contributes to vascular endothelium insulin resistance through stabilizing the PPARγ-NcoR complex[J]. J Cell Physiol,2019,234(11):19663-19674. [21] YAO F,YU Y,FENG L,et al. Adipogenic miR-27a in adipose tissue upregulates macrophage activation via inhibiting PPARγ of insulin resistance induced by high-fat diet-associated obesity[J].Exp Cell Res,2017,355(2):105-112.
