Advanced search
1 file | 81.17 KB

Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models

Author
Organization
Abstract
AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To understand better the physiological role of the catalytic AMPK subunit isoforms, we generated two knockout mouse models with the alpha1 (AMPKalpha1(-/-)) and alpha2 (AMPKalpha2(-/-)) catalytic subunit genes deleted. No defect in glucose homoeostasis was observed in AMPKalpha1(-/-) mice. on the other hand, AMPKalpha2(-/-) mice presented high plasma glucose levels and low plasma insulin concentrations in the fed period and during the glucose tolerance test. Nevertheless, in isolated AMPKalpha2(-/-) pancreatic islets, glucose-stimulated insulin secretion was not affected. Surprisingly, AMPKalpha2(-/-) mice were insulin-resistant and had reduced muscle glycogen synthesis as assessed in vivo by the hyperinsulinaemic euglycaemic clamp procedure. Reduction of insulin sensitivity and glycogen synthesis were not dependent on the lack of AMPK in skeletal muscle, since mice expressing a dominant inhibitory mutant of AMPK in skeletal muscle were not affected and since insulin-stimulated glucose transport in incubated muscles in vitro was normal in AMPKalpha2(-/-) muscles. Furthermore, AMPKalpha2(-/-), mice have a higher sympathetic tone, as shown by increased catecholamine urinary excretion. increased adrenergic tone could explain both decreased insulin secretion and insulin resistance observed in vivo in AMPKalpha2(-/-) mice. We suggest that the alpha2 catalytic subunit of AMPK plays a major role as a fuel sensor by modulating the activity of the autonomous nervous system in vivo.
Keywords
insulin resistance, glucose metabolism, FATTY-ACID OXIDATION, SKELETAL-MUSCLE, GLUCOSE-TRANSPORT, CONTRACTION, CELL, METABOLISM, EXPRESSION

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 81.17 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Viollet, Benoit, Fabrizio Andreelli, Sebastian B Jorgensen, Christophe Perrin, Daisy Flamez, James Mu, Jorgen FP Wojtaszewski, et al. 2003. “Physiological Role of AMP-activated Protein Kinase (AMPK): Insights from Knockout Mouse Models.” Biochemical Society Transactions 31 (1): 216–219.
APA
Viollet, B., Andreelli, F., Jorgensen, S. B., Perrin, C., Flamez, D., Mu, J., Wojtaszewski, J. F., et al. (2003). Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models. BIOCHEMICAL SOCIETY TRANSACTIONS, 31(1), 216–219. Presented at the 2nd International Meeting on AMP-activated Protein Kinase (AMPK 2002).
Vancouver
1.
Viollet B, Andreelli F, Jorgensen SB, Perrin C, Flamez D, Mu J, et al. Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models. BIOCHEMICAL SOCIETY TRANSACTIONS. 2003;31(1):216–9.
MLA
Viollet, Benoit et al. “Physiological Role of AMP-activated Protein Kinase (AMPK): Insights from Knockout Mouse Models.” BIOCHEMICAL SOCIETY TRANSACTIONS 31.1 (2003): 216–219. Print.
@article{847297,
  abstract     = {AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To understand better the physiological role of the catalytic AMPK subunit isoforms, we generated two knockout mouse models with the alpha1 (AMPKalpha1(-/-)) and alpha2 (AMPKalpha2(-/-)) catalytic subunit genes deleted. No defect in glucose homoeostasis was observed in AMPKalpha1(-/-) mice. on the other hand, AMPKalpha2(-/-) mice presented high plasma glucose levels and low plasma insulin concentrations in the fed period and during the glucose tolerance test. Nevertheless, in isolated AMPKalpha2(-/-) pancreatic islets, glucose-stimulated insulin secretion was not affected. Surprisingly, AMPKalpha2(-/-) mice were insulin-resistant and had reduced muscle glycogen synthesis as assessed in vivo by the hyperinsulinaemic euglycaemic clamp procedure. Reduction of insulin sensitivity and glycogen synthesis were not dependent on the lack of AMPK in skeletal muscle, since mice expressing a dominant inhibitory mutant of AMPK in skeletal muscle were not affected and since insulin-stimulated glucose transport in incubated muscles in vitro was normal in AMPKalpha2(-/-) muscles. Furthermore, AMPKalpha2(-/-), mice have a higher sympathetic tone, as shown by increased catecholamine urinary excretion. increased adrenergic tone could explain both decreased insulin secretion and insulin resistance observed in vivo in AMPKalpha2(-/-) mice. We suggest that the alpha2 catalytic subunit of AMPK plays a major role as a fuel sensor by modulating the activity of the autonomous nervous system in vivo.},
  author       = {Viollet, Benoit and Andreelli, Fabrizio and Jorgensen, Sebastian B and Perrin, Christophe and Flamez, Daisy and Mu, James and Wojtaszewski, Jorgen FP and Schuit, Frans C and Birnbaum, Morris J and Richter, Erik A and Burcelin, Rémy and Vaulont, Sophie},
  issn         = {0300-5127},
  journal      = {BIOCHEMICAL SOCIETY TRANSACTIONS},
  keywords     = {insulin resistance,glucose metabolism,FATTY-ACID OXIDATION,SKELETAL-MUSCLE,GLUCOSE-TRANSPORT,CONTRACTION,CELL,METABOLISM,EXPRESSION},
  language     = {eng},
  location     = {Dundee, Scotland, UK},
  number       = {1},
  pages        = {216--219},
  title        = {Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models},
  url          = {http://www.biochemsoctrans.org/bst/031/0216/0310216.pdf},
  volume       = {31},
  year         = {2003},
}

Web of Science
Times cited: