||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, TomoichiroMatsuda, Michiyuki
2638 , 2017-11-28 , Elsevier BV
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.