Imperial College London

ProfessorDavidCarling

Faculty of MedicineInstitute of Clinical Sciences

Professor of Biochemistry
 
 
 
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Contact

 

+44 (0)20 3313 4313david.carling

 
 
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Location

 

3rd Fl CRBHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Johanns:2016:10.1038/ncomms10856,
author = {Johanns, M and Lai, Y-C and Hsu, M-F and Jacobs, R and Vertommen, D and Van, Sande J and Dumont, JE and Woods, A and Carling, D and Hue, L and Viollet, B and Foretz, M and Rider, MH},
doi = {10.1038/ncomms10856},
journal = {Nature Communications},
title = {AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B},
url = {http://dx.doi.org/10.1038/ncomms10856},
volume = {7},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Biguanides such as metformin have previously been shown to antagonize hepatic glucagon-stimulated cyclic AMP (cAMP) signalling independently of AMP-activated protein kinase (AMPK) via direct inhibition of adenylate cyclase by AMP. Here we show that incubation of hepatocytes with the small-molecule AMPK activator 991 decreases glucagon-stimulated cAMP accumulation, cAMP-dependent protein kinase (PKA) activity and downstream PKA target phosphorylation. Moreover, incubation of hepatocytes with 991 increases the Vmax of cyclic nucleotide phosphodiesterase 4B (PDE4B) without affecting intracellular adenine nucleotide concentrations. The effects of 991 to decrease glucagon-stimulated cAMP concentrations and activate PDE4B are lost in hepatocytes deleted for both catalytic subunits of AMPK. PDE4B is phosphorylated by AMPK at three sites, and by site-directed mutagenesis, Ser304 phosphorylation is important for activation. In conclusion, we provide a new mechanism by which AMPK antagonizes hepatic glucagon signalling via phosphorylation-induced PDE4B activation.
AU - Johanns,M
AU - Lai,Y-C
AU - Hsu,M-F
AU - Jacobs,R
AU - Vertommen,D
AU - Van,Sande J
AU - Dumont,JE
AU - Woods,A
AU - Carling,D
AU - Hue,L
AU - Viollet,B
AU - Foretz,M
AU - Rider,MH
DO - 10.1038/ncomms10856
PY - 2016///
SN - 2041-1723
TI - AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/ncomms10856
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000371723800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/30963
VL - 7
ER -