Nov, 2017
A Highly Sensitive FRET Biosensor for AMPK Exhibits Heterogeneous AMPK Responses among Cells and Organs
CELL REPORTS
- Volume
- 21
- Number
- 9
- First page
- 2628
- Last page
- 2638
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1016/j.celrep.2017.10.113
- Publisher
- CELL PRESS
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.
- Link information
- ID information
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- DOI : 10.1016/j.celrep.2017.10.113
- ISSN : 2211-1247
- Pubmed ID : 29186696
- Web of Science ID : WOS:000416979500024