The hypoglycemic mechanism of catalpol involves increased AMPK-mediated mitochondrial biogenesis  

作　　者：Deng-qiu Xu Chun-jie Li Zhen-zhou Jiang Lu Wang Hong-fei Huang Zhi-jian Li Li-xin Sun Si-si Fan Lu-yong Zhang Tao Wang 

机构地区：[1]Jiangsu Key Laboratory of Drug Screening,China Pharmaceutical University,Nanjing 210009,China [2]Key Laboratory of Drug Quality Control and Pharmacovigilance,China Pharmaceutical University,Nanjing 210009,China [3]chool of Pharmacy,China Pharmaceutical University,Nanjing 211198,China [4]Department of Toxicology Laboratory,Xinjiang Institute of Traditional Uyghur Medicine,Xinjiang Laboratory of Uyghur Medical Prescription,Urumqi 830049,China [5]Center for Drug Research and Development,Guangdong Pharmaceutical University,Guangzhou 510006,China [6]Jiangsu Center for Pharmacodynamics Research and Evaluation,China Pharmaceutical University,Nanjing 210009,China

出　　处：《Acta Pharmacologica Sinica》2020年第6期791-799,共9页中国药理学报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(No.81403154,81773827,81573514,81773995,81873084,81573690);the Scholar of the 14th Batch of"Six Talents Peak"High-level Talent Selection program(SWYY-094);the Postgraduate Research Practice Innovation Program of Jiangsu Province(KYCX19-0763);the"Double First-Class"University project(CPU2018GY33);the Qinghai Province High-End Innovative Thousand Talents Program;and theTianshan Cedar Project of the Xinjiang Uygur Autonomous Region(2018XS21).

摘　　要：Mitochondria serve as sensors of energy regulation and glucose levels,which are impaired by diabetes progression.Catalpol is an iridoid glycoside that exerts a hypoglycemic effect by improving mitochondrial function,but the underlying mechanism has not been fully elucidated.In the current study we explored the effects of catalpol on mitochondrial function in db/db mice and C2C12 myotubes in vitro.After oral administration of catalpol(200 mg.kg^-1.d^-1)for 8 weeks,db/db mice exhibited a decreased fasting blood glucose level and restored mitochondrial function in skeletal muscle.Catalpol increased mitochondrial biogenesis,evidenced by significant elevations in the number of mitochondria,mitochondrial DNA levels,and the expression of three genes associated with mitochondrial biogenesis:peroxisome proliferator-activated receptor gammaco-activator 1(PGC-1α),mitochondrial transcription factor A(TFAM)and nuclear respiratory factor 1(NRF1).In C2C12 myotubes,catalpol significantly increased glucose uptake and ATP production.These effects depended on activation of AMP-activated protein kinase(AMPK)-mediated mitochondrial biogenesis.Thus,catalpol improves skeletal muscle mitochondrial function by activating AMPK-mediated mitochondrial biogenesis.These findings may guide the development of a new therapeutic approach for type 2 diabetes.

关 键 词：CATALPOL AMPK MITOCHONDRIA BIOGENESIS type 2 diabetes skeletal muscle 

分 类 号：R96[医药卫生—药理学]