Advanced search
1 file | 485.26 KB Add to list

The AMP-activated protein kinase alpha 2 catalytic subunit controls whole-body insulin sensitivity

Author
Organization
Abstract
AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To better understand the physiological role of AMPK, we generated a knockout mouse model in which the AMPKalpha2 catalytic subunit gene was inactivated. AMPKalpha2(-/-) mice presented high glucose levels in the fed period and during an oral glucose challenge associated with low insulin plasma levels. However, in isolated AMPKalpha2(-/-) pancreatic islets, glucose- and L-arginine-stimulated insulin secretion were not affected. AMPKalpha2(-/-) mice have reduced insulin-stimulated whole-body glucose utilization and muscle glycogen synthesis rates assessed in vivo by the hyperinsulinemic euglycemic clamp technique. Surprisingly, both parameters were not altered in mice expressing a dominant-negative mutant of AMPK in skeletal muscle. Furthermore, glucose transport was normal in incubated isolated AMPKalpha2(-/-) muscles. These data indicate that AMPKalpha2 in tissues other than skeletal muscles regulates insulin action. Concordantly, we found an increased daily urinary catecholamine excretion in AMPKalpha2(-/-) mice, suggesting altered function of the autonomic nervous system that could explain both the impaired insulin secretion and insulin sensitivity observed in vivo. Therefore, extramuscular AMPKalpha2 catalytic subunit is important for whole-body insulin action in vivo, probably through modulation of sympathetic nervous activity.
Keywords
PANCREATIC BETA-CELLS, ACETYL-COA CARBOXYLASE, RAT SKELETAL-MUSCLE, GLUCOSE-UTILIZATION, CONTRACTION, METABOLISM, INFUSION, LEPTIN, INHIBITION, TRANSPORT

Downloads

  • Viollet 2003 JCI 111 1 91.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 485.26 KB

Citation

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

MLA
Viollet, Benoit et al. “The AMP-activated Protein Kinase Alpha 2 Catalytic Subunit Controls Whole-body Insulin Sensitivity.” JOURNAL OF CLINICAL INVESTIGATION 111.1 (2003): 91–98. Print.
APA
Viollet, B., Andreelli, F., Jorgensen, S. B., Perrin, C., Geloen, A., Flamez, D., Mu, J., et al. (2003). The AMP-activated protein kinase alpha 2 catalytic subunit controls whole-body insulin sensitivity. JOURNAL OF CLINICAL INVESTIGATION, 111(1), 91–98.
Chicago author-date
Viollet, Benoit, Fabrizio Andreelli, Sebastian B Jorgensen, Christophe Perrin, Alain Geloen, Daisy Flamez, James Mu, et al. 2003. “The AMP-activated Protein Kinase Alpha 2 Catalytic Subunit Controls Whole-body Insulin Sensitivity.” Journal of Clinical Investigation 111 (1): 91–98.
Chicago author-date (all authors)
Viollet, Benoit, Fabrizio Andreelli, Sebastian B Jorgensen, Christophe Perrin, Alain Geloen, Daisy Flamez, James Mu, Claudia Lenzner, Olivier Baud, Myriam Bennoun, Emmanuel Gomas, Gaël Nicolas, Jorgen FP Wojtaszewski, Axel Kahn, David Carling, Frans C Schuit, Morris J Birnbaum, Erik A Richter, Rémy Burcelin, and Sophie Vaulont. 2003. “The AMP-activated Protein Kinase Alpha 2 Catalytic Subunit Controls Whole-body Insulin Sensitivity.” Journal of Clinical Investigation 111 (1): 91–98.
Vancouver
1.
Viollet B, Andreelli F, Jorgensen SB, Perrin C, Geloen A, Flamez D, et al. The AMP-activated protein kinase alpha 2 catalytic subunit controls whole-body insulin sensitivity. JOURNAL OF CLINICAL INVESTIGATION. 2003;111(1):91–8.
IEEE
[1]
B. Viollet et al., “The AMP-activated protein kinase alpha 2 catalytic subunit controls whole-body insulin sensitivity,” JOURNAL OF CLINICAL INVESTIGATION, vol. 111, no. 1, pp. 91–98, 2003.
@article{847275,
  abstract     = {AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To better understand the physiological role of AMPK, we generated a knockout mouse model in which the AMPKalpha2 catalytic subunit gene was inactivated. AMPKalpha2(-/-) mice presented high glucose levels in the fed period and during an oral glucose challenge associated with low insulin plasma levels. However, in isolated AMPKalpha2(-/-) pancreatic islets, glucose- and L-arginine-stimulated insulin secretion were not affected. AMPKalpha2(-/-) mice have reduced insulin-stimulated whole-body glucose utilization and muscle glycogen synthesis rates assessed in vivo by the hyperinsulinemic euglycemic clamp technique. Surprisingly, both parameters were not altered in mice expressing a dominant-negative mutant of AMPK in skeletal muscle. Furthermore, glucose transport was normal in incubated isolated AMPKalpha2(-/-) muscles. These data indicate that AMPKalpha2 in tissues other than skeletal muscles regulates insulin action. Concordantly, we found an increased daily urinary catecholamine excretion in AMPKalpha2(-/-) mice, suggesting altered function of the autonomic nervous system that could explain both the impaired insulin secretion and insulin sensitivity observed in vivo. Therefore, extramuscular AMPKalpha2 catalytic subunit is important for whole-body insulin action in vivo, probably through modulation of sympathetic nervous activity.},
  author       = {Viollet, Benoit and Andreelli, Fabrizio and Jorgensen, Sebastian B and Perrin, Christophe and Geloen, Alain and Flamez, Daisy and Mu, James and Lenzner, Claudia and Baud, Olivier and Bennoun, Myriam and Gomas, Emmanuel and Nicolas, Gaël and Wojtaszewski, Jorgen FP and Kahn, Axel and Carling, David and Schuit, Frans C and Birnbaum, Morris J and Richter, Erik A and Burcelin, Rémy and Vaulont, Sophie},
  issn         = {0021-9738},
  journal      = {JOURNAL OF CLINICAL INVESTIGATION},
  keywords     = {PANCREATIC BETA-CELLS,ACETYL-COA CARBOXYLASE,RAT SKELETAL-MUSCLE,GLUCOSE-UTILIZATION,CONTRACTION,METABOLISM,INFUSION,LEPTIN,INHIBITION,TRANSPORT},
  language     = {eng},
  number       = {1},
  pages        = {91--98},
  title        = {The AMP-activated protein kinase alpha 2 catalytic subunit controls whole-body insulin sensitivity},
  url          = {http://dx.doi.org/10.1172/JCI200316567},
  volume       = {111},
  year         = {2003},
}

Altmetric
View in Altmetric
Web of Science
Times cited: