学術雑誌論文 A Highly Sensitive FRET Biosensor for AMPK Exhibits Heterogeneous AMPK Responses among Cells and Organs

Konagaya, Yumi  ,  Terai, Kenta  ,  Hirao, Yusuke  ,  Takakura, Kanako  ,  Imajo, Masamichi  ,  Kamioka, Yuji  ,  Sasaoka, Norio  ,  Kakizuka, Akira  ,  Sumiyama, Kenta  ,  Asano, Tomoichiro  ,  Matsuda, Michiyuki

21 ( 9 )  , pp.2628 - 2638 , 2017-11-28 , Elsevier BV
ISSN:2211-1247
内容記述
生きたマウス体内のAMPK活性を可視化 --糖尿病薬や運動が効果を及ぼす細胞が明らかに--. 京都大学プレスリリース. 2017-11-30.
AMP-activated protein kinase (AMPK), a master regulator of cellular metabolism, is a potential target for type 2 diabetes. Although extensive in vitro studies have revealed the complex regulation of AMPK, much remains unknown about the regulation in vivo. We therefore developed transgenic mice expressing a highly sensitive fluorescence resonance energy transfer (FRET)-based biosensor for AMPK, called AMPKAR-EV. AMPKAR-EV allowed us to readily examine the role of LKB1, a canonical stimulator of AMPK, in drug-induced activation and inactivation of AMPK in vitro. In transgenic mice expressing AMPKAR-EV, the AMP analog AICAR activated AMPK in muscle. In contrast, the antidiabetic drug metformin activated AMPK in liver, highlighting the organ-specific action of AMPK stimulators. Moreover, we found that AMPK was activated primarily in fast-twitch muscle fibers after tetanic contraction and exercise. These observations suggest that the AMPKAR-EV mouse will pave a way to understanding the heterogeneous responses of AMPK among cell types in vivo.
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http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/228126/1/j.celrep.2017.10.113.pdf

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