Autor: |
Yumi Konagaya, Kenta Terai, Yusuke Hirao, Kanako Takakura, Masamichi Imajo, Yuji Kamioka, Norio Sasaoka, Akira Kakizuka, Kenta Sumiyama, Tomoichiro Asano, Michiyuki Matsuda |
Jazyk: |
angličtina |
Rok vydání: |
2017 |
Předmět: |
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Zdroj: |
Cell Reports, Vol 21, Iss 9, Pp 2628-2638 (2017) |
Druh dokumentu: |
article |
ISSN: |
2211-1247 |
DOI: |
10.1016/j.celrep.2017.10.113 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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