A Highly Sensitive FRET Biosensor for AMPK Exhibits Heterogeneous AMPK Responses among Cells and Organs

Cell Rep. 2017 Nov 28;21(9):2628-2638. doi: 10.1016/j.celrep.2017.10.113.


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.

Keywords: AMP-activated protein kinase; AMPK; FRET; LKB1; Pin1; cell metabolism; fluorescence resonance energy transfer; live imaging; liver kinase B1; peptidyl-prolyl cis/trans isomerase NIMA-interacting 1.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Biosensing Techniques / methods*
  • Female
  • Fluorescence Resonance Energy Transfer / methods*
  • Liver / metabolism
  • Male
  • Mice
  • Muscle, Skeletal / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology


  • AMP-Activated Protein Kinases