| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 The John B. Pierce Laboratory and 2 Department of Cellular & Molecular Physiology, Yale University, New Haven, Connecticut 06519; and 3 Research Division, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02215
AMP-activated protein kinase
(AMPK) has recently emerged as a key signaling protein in skeletal
muscle, coordinating the activation of both glucose and fatty acid
metabolism in response to increased cellular energy demand. To
determine whether AMPK signaling may also regulate gene
transcription in muscle, rats were given a single
subcutaneous injection (1 mg/g) of the AMP analog
5-aminoimidazole-4-carboxamide-1-
-D-ribonucleoside (AICAR). AICAR injection activated (P < 0.05)
AMPK-
2 (~2.5-fold) and transcription of the uncoupling
protein-3 (UCP3, ~4-fold) and hexokinase II (HKII, ~10-fold) genes
in both red and white skeletal muscle. However, AICAR injection also
elicited (P < 0.05) an acute drop (60%) in blood
glucose and a sustained (2-h) increase in blood lactate, prompting
concern regarding the specificity of AICAR on transcription. To
maximize AMPK activation in muscle while minimizing potential systemic
counterregulatory responses, a single-leg arterial infusion technique
was employed in fully conscious rats. Relative to saline-infused
controls, single-leg arterial infusion of AICAR (0.125, 0.5, and 2.5 µg · g
1 · min1
for 60 min) induced a dose-dependent increase (2- to 4-fold, P < 0.05) in UCP3 and HKII transcription in both red
and white skeletal muscle. Importantly, AICAR infusion activated
transcription only in muscle from the infused leg and had no effect on
blood glucose or lactate levels. These data provide evidence that AMPK signaling is linked to the transcriptional regulation of select metabolic genes in skeletal muscle.
5-aminoimidazole-4-carboxamide ribonucleoside; single-leg arterial infusion; rat; AMP kinase phosphorylation
This article has been cited by other articles:
|
|
 |
|
  D. J. Mazzatti, M. A. Smith, R. C. Oita, F.-L. Lim, A. J. White, and M. B. Reid Muscle unloading-induced metabolic remodeling is associated with acute alterations in PPAR{delta} and UCP-3 expression Physiol Genomics, July 9, 2008; 34(2): 149 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Thomson, S. T. Herway, N. Fillmore, H. Kim, J. D. Brown, J. R. Barrow, and W. W. Winder AMP-activated protein kinase phosphorylates transcription factors of the CREB family J Appl Physiol, February 1, 2008; 104(2): 429 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Lira, Q. A. Soltow, J. H. D. Long, J. L. Betters, J. E. Sellman, and D. S. Criswell Nitric oxide increases GLUT4 expression and regulates AMPK signaling in skeletal muscle Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E1062 - E1068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Pirinen, T. Kuulasmaa, M. Pietila, S. Heikkinen, M. Tusa, P. Itkonen, S. Boman, J. Skommer, A. Virkamaki, E. Hohtola, et al. Enhanced Polyamine Catabolism Alters Homeostatic Control of White Adipose Tissue Mass, Energy Expenditure, and Glucose Metabolism Mol. Cell. Biol., July 1, 2007; 27(13): 4953 - 4967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Krawiec, G. J. Nystrom, R. A. Frost, L. S. Jefferson, and C. H. Lang AMP-activated protein kinase agonists increase mRNA content of the muscle-specific ubiquitin ligases MAFbx and MuRF1 in C2C12 cells Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1555 - E1567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Thomson, B. B. Porter, J. H. Tall, H-J. Kim, J. R. Barrow, and W. W. Winder Skeletal muscle and heart LKB1 deficiency causes decreased voluntary running and reduced muscle mitochondrial marker enzyme expression in mice Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E196 - E202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Jorgensen, J. T. Treebak, B. Viollet, P. Schjerling, S. Vaulont, J. F. P. Wojtaszewski, and E. A. Richter Role of AMPK{alpha}2 in basal, training-, and AICAR-induced GLUT4, hexokinase II, and mitochondrial protein expression in mouse muscle Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E331 - E339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Southworth, K. A. B. Davey, A. Warley, and P. B. Garlick A reevaluation of the roles of hexokinase I and II in the heart Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H378 - H386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sriwijitkamol, J. L. Ivy, C. Christ-Roberts, R. A. DeFronzo, L. J. Mandarino, and N. Musi LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E925 - E932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Lessard, Z.-P. Chen, M. J. Watt, M. Hashem, J. J. Reid, M. A. Febbraio, B. E. Kemp, and J. A. Hawley Chronic rosiglitazone treatment restores AMPK{alpha}2 activity in insulin-resistant rat skeletal muscle Am J Physiol Endocrinol Metab, February 1, 2006; 290(2): E251 - E257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hurst, E. B. Taylor, T. D. Cline, L. J. Greenwood, C. L. Compton, J. D. Lamb, and W. W. Winder AMP-activated protein kinase kinase activity and phosphorylation of AMP-activated protein kinase in contracting muscle of sedentary and endurance-trained rats Am J Physiol Endocrinol Metab, October 1, 2005; 289(4): E710 - E715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Iglesias, S. M. Furler, G. J. Cooney, E. W. Kraegen, and J.-M. Ye AMP-Activated Protein Kinase Activation by AICAR Increases Both Muscle Fatty Acid and Glucose Uptake in White Muscle of Insulin-Resistant Rats In Vivo Diabetes, July 1, 2004; 53(7): 1649 - 1654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yu, N. Fujii, M. F. Hirshman, J. M. Pomerleau, and L. J. Goodyear Cloning and characterization of mouse 5'-AMP-activated protein kinase {gamma}3 subunit Am J Physiol Cell Physiol, February 1, 2004; 286(2): C283 - C292. [Abstract] [Full Text]
|
|
|
|
|
|
M. Suwa, H. Nakano, and S. Kumagai Effects of chronic AICAR treatment on fiber composition, enzyme activity, UCP3, and PGC-1 in rat muscles J Appl Physiol, September 1, 2003; 95(3): 960 - 968. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
