AbMole科研小讲堂丨Metformin：在代谢、肿瘤、衰老与神经疾病动物模型中的多面作用

AbMole科研小讲堂丨Metformin：在代谢、肿瘤、衰老与神经疾病动物模型中的多面作用Metformin（1,1-Dimethylbiguanide，AbMole，M3244）是一种具有广泛研究价值的化合物，其核心作用机制涉及能量代谢的调控与多靶点信号通路的干预。研究表明，Metformin（二甲双胍，AbMole，M2049）可通过抑制线粒体复合物I，减少ATP生成并改善胰岛素敏感性。在能量代谢研究中，Metformin（CASNo.：1115-70-4）通过提高细胞内AMP/ATP比值，变构激活AMP依赖的蛋白激酶（AMPK），进而调控下游糖脂代谢相关基因的表达ADDINEN.CITE<EndNote><Cite><Author>Bailey</Author><Year>2017</Year><RecNum>1491</RecNum><DisplayText><styleface="superscript">1</style></DisplayText><record><rec-number>1491</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764639297">1491</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Bailey,CliffordJ%JDiabetologia</author></authors></contributors><titles><title>Metformin:historicaloverview</title></titles><pages>1566-1576</pages><volume>60</volume><number>9</number><dates><year>2017</year></dates><isbn>0012-186X</isbn><urls></urls></record></Cite><Cite><Author>Kirpichnikov</Author><Year>2002</Year><RecNum>1492</RecNum><record><rec-number>1492</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764639318">1492</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kirpichnikov,Dmitri</author><author>McFarlane,SamyI</author><author>Sowers,JamesR%JAnnalsofinternalmedicine</author></authors></contributors><titles><title>Metformin:anupdate</title></titles><pages>25-33</pages><volume>137</volume><number>1</number><dates><year>2002</year></dates><isbn>0003-4819</isbn><urls></urls></record></Cite></EndNote>1。Metformin在动物疾病模型的研究中具有广泛的应用，包括肿瘤、肝病、肥胖、心血管疾病、年龄相关疾病、肾脏疾病、糖尿病等多种动物模型。Metformin（二甲双胍，AbMole，M2049）通过多种不同的分子机制，在上述一系列疾病模型中发挥作用。例如在细胞和动物的研究中发现，二甲双胍抑制了AMPK依赖途径或独立途径中糖生成基因的表达，从而抑制肝脏葡萄糖的产生。此外，二甲双胍还可通过限制乳酸的生物利用增强葡萄糖的运输和吸收，或改变肠道微生物群，降低小鼠的血糖水平。Metformin还可用于抑制肿瘤细胞的生长、存活和转移，同时改变肿瘤微环境以抑制癌症的发展，其分子机制包括抑制mTOR信号、p53激活、自噬和诱导凋亡、ROS生成、DNA损伤和改善肿瘤的免疫微环境ADDINEN.CITE<EndNote><Cite><Author>Wu</Author><Year>2022</Year><RecNum>1495</RecNum><DisplayText><styleface="superscript">2,3</style></DisplayText><record><rec-number>1495</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764640433">1495</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Wu,Zihong</author><author>Zhang,Caidie</author><author>Najafi,Masoud%JJournalofcellcommunication</author><author>signaling</author></authors></contributors><titles><title>Targetingofthetumorimmunemicroenvironmentbymetformin</title></titles><pages>333-348</pages><volume>16</volume><number>3</number><dates><year>2022</year></dates><isbn>1873-9601</isbn><urls></urls></record></Cite><Cite><Author>Lv</Author><Year>2020</Year><RecNum>1494</RecNum><record><rec-number>1494</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764640379">1494</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lv,Ziquan</author><author>Guo,Yajie</author></authors></contributors><titles><title>MetforminandItsBenefitsforVariousDiseases</title><short-title>Metformin’sbenefitsondiseases</short-title></titles><volume>Volume11-2020</volume><keywords><keyword>Metformin,Benefits,Diseases,MitochondrialrespiratorychaincomplexI,AMPK</keyword></keywords><dates><year>2020</year><pub-dates><date>2020-April-16</date></pub-dates></dates><isbn>1664-2392</isbn><work-type>Review</work-type><urls><related-urls><url>/journals/endocrinology/articles/10.3389/fendo.2020.00191</url></related-urls></urls><electronic-resource-num>10.3389/fendo.2020.00191</electronic-resource-num><language>English</language></record></Cite></EndNote>2,3。Metformin（二甲双胍，AbMole，M2049）在衰老的小鼠和线虫模型中，还能够降低ROS、减少DNA损伤、抑制炎症反应和细胞自噬ADDINEN.CITE<EndNote><Cite><Author>Barzilai</Author><Year>2016</Year><RecNum>1496</RecNum><DisplayText><styleface="superscript">4</style></DisplayText><record><rec-number>1496</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764640600">1496</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Barzilai,Nir</author><author>Crandall,JillP</author><author>Kritchevsky,StephenB</author><author>Espeland,MarkA%JCellmetabolism</author></authors></contributors><titles><title>Metforminasatooltotargetaging</title></titles><pages>1060-1065</pages><volume>23</volume><number>6</number><dates><year>2016</year></dates><isbn>1550-4131</isbn><urls></urls></record></Cite></EndNote>4。在神经科学研究中，Metformin在APP/PS1转基因阿尔茨海默症模型小鼠中被用于评估其对脑能量代谢和海马神经元突触可塑性的潜在影响，结果证实Metformin改善了小鼠的淀粉样斑块的沉积和小鼠的记忆障碍ADDINEN.CITE<EndNote><Cite><Author>Ou</Author><Year>2018</Year><RecNum>1493</RecNum><DisplayText><styleface="superscript">5</style></DisplayText><record><rec-number>1493</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764640281">1493</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Ou,Zhenri</author><author>Kong,Xuejian</author><author>Sun,Xiangdong</author><author>He,Xiaosong</author><author>Zhang,Le</author><author>Gong,Zhuo</author><author>Huang,Jingyi</author><author>Xu,Biao</author><author>Long,Dahong</author><author>Li,Jianhua%JBrain,behavior,</author><author>immunity</author></authors></contributors><titles><title>MetformintreatmentpreventsamyloidplaquedepositionandmemoryimpairmentinAPP/PS1mice</title></titles><pages>351-363</pages><volume>69</volume><dates><year>2018</year></dates><isbn>0889-1591</isbn><urls></urls></record></Cite></EndNote>5。Metformin在多种动物疾病模型中的应用及其作用机制ADDINEN.CITE<EndNote><Cite><Author>Lv</Author><Year>2020</Year><RecNum>1494</RecNum><DisplayText><styleface="superscript">3</style></DisplayText><record><rec-number>1494</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764640379">1494</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lv,Ziquan</author><author>Guo,Yajie</author></authors></contributors><titles><title>MetforminandItsBenefitsforVariousDiseases</title><short-title>Metformin’sbenefitsondiseases</short-title></titles><volume>Volume11-2020</volume><keywords><keyword>Metformin,Benefits,Diseases,MitochondrialrespiratorychaincomplexI,AMPK</keyword></keywords><dates><year>2020</year><pub-dates><date>2020-April-16</date></pub-dates></dates><isbn>1664-2392</isbn><work-type>Review</work-type><urls><related-urls><url>/journals/endocrinology/articles/10.3389/fendo.2020.00191</url></related-urls></urls><electronic-resource-num>10.3389/fendo.2020.00191</electronic-resource-num><language>English</language></record></Cite></EndNote>3范例详解Metabolism.2023Mar;140:155398.中国科技大学的研究团队在上述论文中使用了AbMole的Metformin（二甲双胍;1,1-Dimethylbiguanide，M3244），探究了间充质干细胞（MSCs）联合纤维蛋白支架（MSCs/FG）与Metformin在糖尿病伤口愈合中的作用及机制，发现二者协同通过Akt/mTOR通路促进VEGF介导的血管生成，且Metformin呈现剂量依赖性效应ADDINEN.CITEADDINEN.CITE.DATA6。Thedose-dependenteffectsofmetformin(MTF)ontheAkt/mTORactivationandmigrationinfibroblastsandkeratinocytesADDINEN.CITEADDINEN.CITE.DATA6.AbMole是ChemBridge中国区官方指定合作伙伴。*本文所述产品仅供科研使用参考文献及鸣谢ADDINEN.REFLIST(1)Bailey,C.J.J.D.Metformin:historicaloverview.2017,60(9),1566-1576.Kirpichnikov,D.;McFarlane,S.I.;Sowers,J.R.J.A.o.i.m.Metformin:anupdate.2002,137(1),25-33.(2)Wu,Z.;Zhang,C.;Najafi,M.J.J.o.c.c.;signaling.Targetingofthetumorimmunemicroenvironmentbymetformin.2022,16(3),333-3