Activation of Skeletal Muscle AMPK Promotes Glucose Disposal and Glucose Lowering in Non-human Primates and Mice.
Emily C Cokorinos
1
,
Jake Delmore
1
,
Allan R. Reyes
1
,
Bina Albuquerque
1
,
Rasmus Kjobsted
2
,
Nicolas O Jørgensen
2
,
Jean-Luc Tran
1
,
Aditi Jatkar
1
,
Katherine Cialdea
1
,
Ryan M Esquejo
1
,
John Meissen
3
,
Matthew F Calabrese
4
,
Jason Cordes
5
,
Robert Moccia
6
,
David Tess
7
,
Christopher T. Salatto
1
,
Timothy M Coskran
5
,
Alan C. Opsahl
5
,
Declan Flynn
5
,
Matthew Blatnik
3
,
Wenlin Li
8
,
Erick Kindt
8
,
Marc Foretz
9, 10, 11
,
Benoit Viollet
9, 10, 11
,
Jessica Ward
1
,
Ravi G. KURUMBAIL
4
,
A. Kalgutkar
7
,
E. A. Richter
2
,
Kimberly O. Cameron
12
,
Russell A Miller
1
1
Cardiovascular, Metabolic, and Endocrine Diseases Research Unit, Pfizer Inc., Cambridge, MA 02139, USA
|
3
Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc, Groton, CT 06340, USA.
|
4
Worldwide Medicinal Chemistry, Pfizer Worldwide Research & Development, Pfizer Inc., Groton, CT 06340, USA
|
5
Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 USA.
|
6
Computational Sciences, Pfizer Inc., Cambridge, MA 02139, USA
|
7
Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc., Cambridge, MA 02139, USA
|
8
Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc., San Diego, CA 92121, USA.
|
9
CNRS, UMR8104, Paris 75016, France
|
10
12
Cardiovascular, Metabolic, and Endocrine Diseases Medicinal Chemistry, Pfizer Inc., Cambridge, MA 02139, USA.
|
Publication type: Journal Article
Publication date: 2017-05-02
scimago Q1
wos Q1
SJR: 11.989
CiteScore: 45.5
Impact factor: 30.9
ISSN: 15504131, 19327420
PubMed ID:
28467931
Molecular Biology
Cell Biology
Physiology
Abstract
The AMP-activated protein kinase (AMPK) is a potential therapeutic target for metabolic diseases based on its reported actions in the liver and skeletal muscle. We evaluated two distinct direct activators of AMPK: a non-selective activator of all AMPK complexes, PF-739, and an activator selective for AMPK β1-containing complexes, PF-249. In cells and animals, both compounds were effective at activating AMPK in hepatocytes, but only PF-739 was capable of activating AMPK in skeletal muscle. In diabetic mice, PF-739, but not PF-249, caused a rapid lowering of plasma glucose levels that was diminished in the absence of skeletal muscle, but not liver, AMPK heterotrimers and was the result of an increase in systemic glucose disposal with no impact on hepatic glucose production. Studies of PF-739 in cynomolgus monkeys confirmed translation of the glucose lowering and established activation of AMPK in skeletal muscle as a potential therapeutic approach to treat diabetic patients.
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Total citations:
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Citations from 2024:
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Cokorinos E. C. et al. Activation of Skeletal Muscle AMPK Promotes Glucose Disposal and Glucose Lowering in Non-human Primates and Mice. // Cell Metabolism. 2017. Vol. 25. No. 5. p. 1147-1159.e10.
GOST all authors (up to 50)
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Cokorinos E. C., Delmore J., Reyes A., Albuquerque B., Kjobsted R., Jørgensen N. O., Tran J., Jatkar A., Cialdea K., Esquejo R. M., Meissen J., Calabrese M. F., Cordes J., Moccia R., Tess D., Salatto C. T., Coskran T. M., Opsahl A. C., Flynn D., Blatnik M., Li W., Kindt E., Foretz M., Viollet B., Ward J., KURUMBAIL R. G., Kalgutkar A., Richter E. A., Cameron K. O., Miller R. A. Activation of Skeletal Muscle AMPK Promotes Glucose Disposal and Glucose Lowering in Non-human Primates and Mice. // Cell Metabolism. 2017. Vol. 25. No. 5. p. 1147-1159.e10.
Cite this
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TY - JOUR
DO - 10.1016/j.cmet.2017.04.010
UR - https://doi.org/10.1016/j.cmet.2017.04.010
TI - Activation of Skeletal Muscle AMPK Promotes Glucose Disposal and Glucose Lowering in Non-human Primates and Mice.
T2 - Cell Metabolism
AU - Cokorinos, Emily C
AU - Delmore, Jake
AU - Reyes, Allan R.
AU - Albuquerque, Bina
AU - Kjobsted, Rasmus
AU - Jørgensen, Nicolas O
AU - Tran, Jean-Luc
AU - Jatkar, Aditi
AU - Cialdea, Katherine
AU - Esquejo, Ryan M
AU - Meissen, John
AU - Calabrese, Matthew F
AU - Cordes, Jason
AU - Moccia, Robert
AU - Tess, David
AU - Salatto, Christopher T.
AU - Coskran, Timothy M
AU - Opsahl, Alan C.
AU - Flynn, Declan
AU - Blatnik, Matthew
AU - Li, Wenlin
AU - Kindt, Erick
AU - Foretz, Marc
AU - Viollet, Benoit
AU - Ward, Jessica
AU - KURUMBAIL, Ravi G.
AU - Kalgutkar, A.
AU - Richter, E. A.
AU - Cameron, Kimberly O.
AU - Miller, Russell A
PY - 2017
DA - 2017/05/02
PB - Elsevier
SP - 1147-1159.e10
IS - 5
VL - 25
PMID - 28467931
SN - 1550-4131
SN - 1932-7420
ER -
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@article{2017_Cokorinos,
author = {Emily C Cokorinos and Jake Delmore and Allan R. Reyes and Bina Albuquerque and Rasmus Kjobsted and Nicolas O Jørgensen and Jean-Luc Tran and Aditi Jatkar and Katherine Cialdea and Ryan M Esquejo and John Meissen and Matthew F Calabrese and Jason Cordes and Robert Moccia and David Tess and Christopher T. Salatto and Timothy M Coskran and Alan C. Opsahl and Declan Flynn and Matthew Blatnik and Wenlin Li and Erick Kindt and Marc Foretz and Benoit Viollet and Jessica Ward and Ravi G. KURUMBAIL and A. Kalgutkar and E. A. Richter and Kimberly O. Cameron and Russell A Miller},
title = {Activation of Skeletal Muscle AMPK Promotes Glucose Disposal and Glucose Lowering in Non-human Primates and Mice.},
journal = {Cell Metabolism},
year = {2017},
volume = {25},
publisher = {Elsevier},
month = {may},
url = {https://doi.org/10.1016/j.cmet.2017.04.010},
number = {5},
pages = {1147--1159.e10},
doi = {10.1016/j.cmet.2017.04.010}
}
Cite this
MLA
Copy
Cokorinos, Emily C., et al. “Activation of Skeletal Muscle AMPK Promotes Glucose Disposal and Glucose Lowering in Non-human Primates and Mice..” Cell Metabolism, vol. 25, no. 5, May. 2017, pp. 1147-1159.e10. https://doi.org/10.1016/j.cmet.2017.04.010.