Article(id=1220655291440481131, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1220655289922143078, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2020-0001, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1577894400000, receivedDateStr=2020-01-02, revisedDate=1582473600000, revisedDateStr=2020-02-24, acceptedDate=null, acceptedDateStr=null, onlineDate=1768956500158, onlineDateStr=2026-01-21, pubDate=1591891200000, pubDateStr=2020-06-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1768956500158, onlineIssueDateStr=2026-01-21, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1768956500158, creator=13701087609, updateTime=1768956500158, updator=13701087609, issue=Issue{id=1220655289922143078, tenantId=1146029695717560320, journalId=1189982191388893191, year='2020', volume='55', issue='6', pageStart='1073', pageEnd='1356', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1768956499796, creator=13701087609, updateTime=1768957205309, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1220658249112671213, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1220655289922143078, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1220658249112671214, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1220655289922143078, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1209, endPage=1213, ext={EN=ArticleExt(id=1220655292438725499, articleId=1220655291440481131, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Exendin-4 promotes the anti-diabetic effects of puerarin in high fat diet diabetic mice, columnId=1190335348761793317, journalTitle=Acta Pharmaceutica Sinica, columnName=Original Articles, runingTitle=null, highlight=null, articleAbstract=
Our previous report demonstrated puerarin protected β cells by up-regulating the expression of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R). However, whether the anti-diabetic effects of puerarin in vivo depend on GLP-1R activation has not been clarified. In this study, the GLP-1R agonist exendin-4 (Ex4) and the GLP-1R antagonist exendin 9-39 (Ex9-30) were used. Type 2 diabetes was induced in C57BL/6J mice by a high fat diet (HFD) and divided into the following groups: control, HFD, HFD/puerarin (300 mg·kg-1·d-1), HFD/puerarin/exendin 9-39 (Ex9-39: 10 nmol·kg-1·d-1), and HFD/puerarin/exendin-4 group (Ex4: 10 nmol·kg-1·d-1). Animal experiments were approved by the Research Animal Care Committee of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine (AEWC-025). Puerarin was administered orally, Ex9-39 and Ex4 were administered by intraperitoneal injection for 10 days. Compared with HFD group, after 10-day treatment, the fasting blood glucose and oral glucose tolerance test (OGTT) of diabetic mice were effectively improved by puerarin (P < 0.05). Meanwhile, serum insulin levels were increased by puerarin, and levels of glucagon, triglycerides, and total cholesterol were significantly reduced (P < 0.05). Importantly, Ex4 significantly enhanced the anti-diabetic effects of puerarin in HFD mice, while Ex9-39 markedly inhibited the effects of puerarin (P < 0.05), which indicates that the effects of puerarin depend on GLP-1R activation. Furthermore, results of Western blotting of liver tissue showed puerarin effectively activated AKT and inhibited FOXO1, which relied on GLP-1R activation as well. Taken together, our findings demonstrate that puerarin ameliorates glucose homeostasis in HFD mice and is dependent on GLP-1R activation. This study provides experimental support for the potential application of puerarin.
, correspAuthors=Luan SHU, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2020 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Ji-hong YAO, Jing WANG, Zi-qi HU, Luan SHU), CN=ArticleExt(id=1220655293680239537, articleId=1220655291440481131, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=艾塞那肽促进葛根素改善高脂饮食糖尿病模型小鼠糖代谢作用的研究, columnId=1190335348896011050, journalTitle=药学学报, columnName=研究论文, runingTitle=null, highlight=null, articleAbstract=
前期研究发现葛根素通过上调胰岛β细胞GLP-1R（GLP-1 receptor）的表达保护β细胞，但葛根素综合降糖作用是否受到GLP-1R激活调控，尚未验证。本文采用GLP-1R激动剂艾塞那肽（exendin-4，Ex4）与GLP-1R拮抗剂毒蜥外泌肽9-39（exendin 9-39，Ex9-39），以高脂饮食（high-fat diet，HFD）诱导小鼠糖尿病模型，实验分为对照组、高脂组、高脂/葛根素组（300 mg·kg-1·d-1）、高脂/葛根素/Ex9-39组（Ex9-39：10 nmol·kg-1·d-1）、高脂/葛根素/Ex4组（Ex4：10 nmol·kg-1·d-1）。动物实验已获得南京中医药大学附属中西医结合医院动物伦理委员会批准（AEWC-025）。葛根素灌胃给药，Ex9-39与Ex4腹腔注射给药。给药10天，考察小鼠空腹血糖及口服葡萄糖耐量（oral glucose tolerance test，OGTT），测定血清胰岛素等指标，检测肝脏AKT及FOXO1的变化。与高脂组相比，葛根素组小鼠空腹血糖与OGTT均得到有效改善，血清胰岛素水平升高，而胰高血糖素、甘油三酯及总胆固醇均显著降低（P < 0.05）。Ex4对葛根素综合降糖的多项指标具有显著增强作用，而Ex9-39明显抑制葛根素的作用（P < 0.05），提示葛根素作用依赖于GLP-1R激活。Western blotting分析显示，葛根素有效激活肝组织中AKT分子，并抑制转录因子FOXO1活性，其作用同样被Ex4有效促进，而被Ex9-39显著抑制。本研究表明，葛根素可通过激活GLP-1R通路改善HFD糖尿病小鼠的糖代谢，为葛根素的开发应用提供实验支撑。
, correspAuthors=舒娈, authorNote=null, correspAuthorsNote=
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The fasting body weights (A) and blood glucose levels (B) of mice after 10 days treatment. <i>n</i> = 6-8, $\bar{x} \pm s$. <sup>*</sup><i>P</i> < 0.05 <i>vs</i> Con; <sup>#</sup><i>P</i> < 0.05 <i>vs</i> HFD saline; <sup>^</sup><i>P</i> < 0.05 <i>vs</i> HFD/pue. HFD: High fat diet; Ex9-39: Exendin 9-39; Ex4: Exendin-4; pue: Puerarin , figureFileSmall=o6UDba/POQj2NpCHEmHZ4w==, figureFileBig=Ujz+u/yvwSHtoc6dn4s5pw==, tableContent=null), ArticleFig(id=1220655297006321895, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655291440481131, language=EN, label=null, caption=null, figureFileSmall=u+lSEVa2c043HPDt+7SZgg==, figureFileBig=pobUqkFkalrV9D3Jaqzszw==, tableContent=null), ArticleFig(id=1220655297098596591, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655291440481131, language=CN, label=Figure 2, caption=
The results of oral glucose tolerance test (OGTT) (A) and area under curve (AUC) (B) after 10 days treatment. <i>n</i> = 6-8, $\bar{x} \pm s$. <sup>*</sup><i>P</i> < 0.05 <i>vs</i> Con; <sup>#</sup><i>P</i> < 0.05 <i>vs</i> HFD saline; <sup>^</sup><i>P</i> < 0.05 <i>vs</i> HFD/pue , figureFileSmall=u+lSEVa2c043HPDt+7SZgg==, figureFileBig=pobUqkFkalrV9D3Jaqzszw==, tableContent=null), ArticleFig(id=1220655297203454204, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655291440481131, language=EN, label=null, caption=null, figureFileSmall=Ch0DT8MSHBihryWBsXwpoQ==, figureFileBig=T/NXenO6WKABENb9HXaNeQ==, tableContent=null), ArticleFig(id=1220655297341866253, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655291440481131, language=CN, label=Figure 3, caption=
The impacts of puerarin, Ex9-39 or Ex4 on serum insulin (A) and glucagon (B) levels of mice after 10 days treatment. <i>n</i> = 6-8, $\bar{x} \pm s$. <sup>*</sup><i>P</i> < 0.05 <i>vs</i> Con; <sup>#</sup><i>P</i> < 0.05 <i>vs</i> HFD saline; <sup>^</sup><i>P</i> < 0.05 <i>vs</i> HFD/pue , figureFileSmall=Ch0DT8MSHBihryWBsXwpoQ==, figureFileBig=T/NXenO6WKABENb9HXaNeQ==, tableContent=null), ArticleFig(id=1220655297543192854, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655291440481131, language=EN, label=null, caption=null, figureFileSmall=Zrp6F/OOVvPrH2JbzucPAw==, figureFileBig=XH+n0KY0W1C/JKNcRkvywQ==, tableContent=null), ArticleFig(id=1220655297652244769, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655291440481131, language=CN, label=Figure 4, caption=
The effects of puerarin, Ex9-39 or Ex4 on the lipid metabolism of HFD mice. (A) Levels of serum triglycerol (TG), and (B) levels of serum cholesterol (CHO) of mice after 10 days treatment. <i>n</i> = 6-8, $\bar{x} \pm s$. <sup>*</sup><i>P</i> < 0.05 <i>vs</i> Con; <sup>#</sup><i>P</i> < 0.05 <i>vs</i> HFD saline; <sup>^</sup><i>P</i> < 0.05 <i>vs</i> HFD/pue , figureFileSmall=Zrp6F/OOVvPrH2JbzucPAw==, figureFileBig=XH+n0KY0W1C/JKNcRkvywQ==, tableContent=null), ArticleFig(id=1220655297803239729, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655291440481131, language=EN, label=null, caption=null, figureFileSmall=iVc5G7oyg62hbMiLwGzgsQ==, figureFileBig=J/tgHv4VwZxkJxf+6mkUWw==, tableContent=null), ArticleFig(id=1220655297908097338, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655291440481131, language=CN, label=Figure 5, caption=
Results of Western blotting assays (A) and comparing changes (B) of p-AKT and p-FOXO1 in liver samples of mice. (A) The representative pictures of Western blotting assays were shown. 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