Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McGee, S. L.
Right arrow Articles by Hargreaves, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McGee, S. L.
Right arrow Articles by Hargreaves, M.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 52:926-928, 2003
© 2003 by the American Diabetes Association, Inc.

Exercise Increases Nuclear AMPK {alpha}2 in Human Skeletal Muscle

Sean L. McGee1, Kirsten F. Howlett1, Rebecca L. Starkie1, David Cameron-Smith1, Bruce E. Kemp2, and Mark Hargreaves1

1 Exercise, Muscle and Metabolism Unit, School of Health Sciences, Deakin University, Burwood, Australia
2 St. Vincent’s Institute of Medical Research, St. Vincent’s Hospital, Fitzroy, Victoria, Australia


   ABSTRACT
TOP
 ABSTRACT
RESEARCH DESIGN AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
An acute bout of exercise increases skeletal muscle glucose uptake, improves glucose homeostasis and insulin sensitivity, and enhances muscle oxidative capacity. Recent studies have shown an association between these adaptations and the energy-sensing 5' AMP-activated protein kinase (AMPK), the activity of which is increased in response to exercise. Activation of AMPK has been associated with enhanced expression of key metabolic proteins such as GLUT-4, hexokinase II (HKII), and mitochondrial enzymes, similar to exercise. It has been hypothesized that AMPK might regulate gene and protein expression through direct interaction with the nucleus. The purpose of this study was to determine if nuclear AMPK {alpha}2 content in human skeletal muscle was increased by exercise. Following 60 min of cycling at 72 ± 1% of VO2peak in six male volunteers (20.6 ± 2.1 years; 72.9 ± 2.1 kg; VO2peak = 3.62 ± 0.18 l/min), nuclear AMPK {alpha}2 content was increased 1.9 ± 0.4-fold (P = 0.024). There was no change in whole-cell AMPK {alpha}2 content or AMPK {alpha}2 mRNA abundance. These results suggest that nuclear translocation of AMPK might mediate the effects of exercise on skeletal muscle gene and protein expression.

An acute bout of exercise increases skeletal muscle glucose uptake, improves glucose homeostasis and insulin sensitivity, and enhances muscle oxidative capacity. These positive metabolic adaptations have also been observed in insulin-resistant states and type 2 diabetic subjects and may partly explain the well-recognized benefits of physical activity in the prevention and management of type 2 diabetes (1). Recent studies have shown an association between these adaptations and the energy-sensing 5' AMP-activated protein kinase (AMPK). AMPK is a heterotrimer, consisting of {alpha}, ß, and {gamma} subunits, that is activated in response to increases in the AMP-to-ATP ratio (2). There are two {alpha}, two ß, and three {gamma} isoforms capable of forming AMPK complexes, with skeletal muscle predominantly expressing the {alpha}2, ß2, and {gamma}1 isoforms (2). AMPK complexes containing the catalytic {alpha}2 subunit are preferentially activated during exercise at intensities >70% VO2peak, in both normal (3) and type 2 diabetic subjects (4). Long-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a drug that activates AMPK, to insulin-resistant Zucker rats improves glucose tolerance and other symptoms associated with the disease (5). AICAR administration also increases the expression of several key regulatory proteins involved in glucose metabolism, such as GLUT-4 (6), hexokinase II (HKII [6]), and mitochondrial enzymes (7), similar to exercise training. Consequently, it has been thought that AMPK might mediate the positive effects of exercise on skeletal muscle glucose metabolism through regulation of gene and protein expression. This hypothesis is consistent with the function of the AMPK yeast homologue Snf1, which is known to regulate a range of metabolic genes (8). Snf1 regulates gene transcription by directly phosphorylating nuclear transcription factors (8). Similarly, AMPK complexes containing the {alpha}2 subunit are preferentially localized to the nucleus (9). Furthermore, inhibition of not only nuclear but also cytosolic AMPK {alpha}2 in islet ß-cell cultures is required to relieve inhibition of liver-type pyruvate kinase (L-PK) expression by AMPK (10). This suggests that AMPK translocates to the nucleus where it could then interact with transcriptional regulators, or DNA directly, to control gene expression. Therefore, the purpose of this study was to determine if nuclear AMPK {alpha}2 content was increased in human skeletal muscle following an acute bout of exercise, which we have previously shown to increase GLUT-4 gene expression (11). We hypothesized that exercise would increase nuclear AMPK {alpha}2 abundance.


   RESEARCH DESIGN AND METHODS
TOP
 ABSTRACT
 RESEARCH DESIGN AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects.
Six active, but untrained, male subjects (20.6 ± 2.1 years; 72.9 ± 2.1 kg; 180 ± 3 cm) were recruited for the study after completing a medical questionnaire and giving their informed written consent. All experimental procedures were approved by the Deakin University Human Research Ethics Committee. At least 7 days before the experimental trial, all subjects performed an incremental cycling (Lode, Groningen, the Netherlands) test to fatigue to determine VO2peak, which averaged 3.62 ± 0.18 l/min. This test was also used to select the power output for the experimental trial from the linear relationship between oxygen uptake and power output.

Exercise.
Subjects performed 60 min of cycling at ~70% VO2peak after a 12-h overnight fast. Expired air was collected twice, at 15–20 and 40–45 min, to ensure that subjects were exercising at the expected exercise intensity. Subjects ingested tap water ad libitum throughout the exercise bout.

Muscle biopsies.
Muscle samples were obtained from the vastus lateralis before exercise, after 10 min of exercise, and immediately following exercise using the percutaneous needle biopsy technique with suction (12). Muscle samples were immediately frozen in liquid nitrogen and stored for later analysis.

Skeletal muscle fractionation.
Nuclear proteins were isolated using a modification of the protocol by Blough et al. (13). Approximately 40 mg of muscle was homogenized in 500 µl of ice-cold buffer A (250 mmol/l sucrose, 10 mmol/l NaCl, 3 mmol/l MgCl2, 1 mmol/l dithiothreitol (DTT), 1 mmol/l PMSF [phenylmethylsulfonyl flouride], and 2 µl/40 mg tissue protease inhibitor cocktail), on ice for ~30 s. The homogenate was then spun in a centrifuge for 5 min at 500g at 4°C. The supernatant, representing a crude fraction, was extracted and stored. The remaining pellet was resuspended in 500 µl of ice-cold buffer B (50 mmol/l Tris, pH 7.5, 1 mmol/l EDTA, 1 mmol/l EGTA, 1 mmol/l DTT, 50 mmol/l NaF, 5 mmol/l Na pyrophosphate, 50 mmol/l MgCl2, 10% glycerol, 1% Triton X-100, 1 mmol/l PMSF, and 2 µl/40 mg tissue protease inhibitor cocktail) and placed on ice for 10 min, with occasional mixing. The resuspended pellet was spun in a centrifuge for 5 min at 3,000g at 4°C. The supernatant, representing the nuclear fraction, was extracted and stored. Fraction purity was verified by immunoblotting for the nuclear histone 1 (H1), the plasma membrane mitochondrial bound creatine transporter (CreaT), and the plasma membrane and cytosolic GLUT-4. Results are not shown, but the nuclear fraction was dominant for H1 but negative for CreaT and GLUT-4. In contrast, the crude fraction was positive for CreaT and GLUT-4 but negative for H1.

Immunoblotting.
Proteins were separated and identified using SDS-PAGE. From each sample, 150 µg of protein was loaded onto 1.5 mm 8% acrylamide gels before undergoing electrophoresis for 70 min at 180 V. Proteins were semi-dry–transferred to a nitrocellulose membrane for 2 h at 50 mA. Membranes were blocked for 1 h in blocking buffer (5% skim milk powder in Tris-buffered saline with 0.25% Tween [TBST]) and exposed overnight at 4°C to AMPK {alpha}2 primary antibodies as previously described (14). Membranes were exposed to anti-rabbit horseradish peroxidase–conjugated secondary antibodies at a concentration of 1 in 10,000 in blocking buffer for 60 min. Antibody binding was viewed by enhanced chemiluminescence substrate (Pierce SuperSignal Chemiluminescent; Pierce, Rockford, IL) and a Kodak Image Station 440CF (NEN Life Science Products, Boston, MA). Bands were identified and quantified using Kodak 1D Image Analysis Software (Eastman Kodak, Rochester, NY).

Real time RT-PCR.
Total RNA was extracted from ~10 mg of muscle using the acid guanidium thiocyanate-phenol-chloroform extraction technique with modifications (FastRNA Kit-Green; Bio101, Carlsbad, CA). Oligo dT single-stranded cDNA was synthesized using AMV Reverse Transcriptase Kit (Promega A3500, Madison, WI). Forward and reverse primers complimentary to the human AMPK {alpha}2 gene (GenBank M20747) were designed using Primer Express software (PE Applied Biosystems, Foster City, CA). The AMPK {alpha}2 forward primer sequence (5' to 3') was GGG TGA AGA TCG GAC ACT ACG T, while the reverse primer sequence was TTG ATG TTC AAT CTT CAC TTT G. Real-time RT-PCR was performed using the GeneAmp 5700 sequence detector and software (PE Applied Biosystems). Changes in AMPK {alpha}2 gene expression were normalized to the housekeeping gene ß-actin.

Statistical analyses.
All values reported are means ± SEM. One-way ANOVA and least squared difference post hoc tests were used with a significance level of 0.05.


   RESULTS
TOP
 ABSTRACT
 RESEARCH DESIGN AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Subjects undertook 60 min of exercise at a workload that elicited a mean absolute oxygen uptake of 2.62 ± 0.11 l/min corresponding to 72 ± 1% of VO2peak. Nuclear AMPK {alpha}2 content after 10 min of exercise was not different compared with rest. However, nuclear AMPK {alpha}2 content was increased 1.9 ± 0.4-fold (P < 0.05) after 60 min of exercise compared with rest (Fig. 1A). Whole-cell AMPK {alpha}2 protein (Fig. 1B) was similar after 10 and 60 min of exercise when compared with rest. Similarly, AMPK {alpha}2 mRNA, expressed as a ratio to mRNA of the housekeeping gene ß-actin, was similar after 10 and 60 min of exercise when compared with rest (data not shown).



View larger version (14K):
[in this window]
[in a new window]
  		FIG. 1. Nuclear (A) and total (B) AMPK {alpha}2 protein in response to exercise. All values are calculated as the fold changes relative to rest and reported as the means ± SEM (n = 6). *Significantly different from rest (P = 0.024) and 10 min (P = 0.029).

 

   DISCUSSION
TOP
 ABSTRACT
 RESEARCH DESIGN AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
It has previously been shown that GLUT-4 (11), HKII (15), and mitochondrial enzyme (16) mRNA is increased immediately after exercise. Activation of AMPK by AICAR also increases expression of these key metabolic proteins (6,7,17,18). The similarity between the effects of exercise and AMPK activation through AICAR on the regulated expression of these proteins has led to the hypothesis that AMPK might mediate the effects of exercise on skeletal muscle gene and protein expression. It has been unclear whether AMPK {alpha}2 directly targets nuclear transcription factors, or downstream cytosolic proteins, for this purpose. The results of this study demonstrate for the first time that nuclear AMPK {alpha}2 content is increased following an exercise bout that is known to both activate the {alpha}2 isoenzyme and induce GLUT-4 gene expression. As whole-cell AMPK {alpha}2 content was not changed, it appears that the increase in nuclear AMPK {alpha}2 content with exercise was the result of nuclear translocation.

The molecular mechanisms underlying the nuclear translocation of AMPK were not examined in the present study. However, in cultured HEK-293 cells it has previously been found that dephosphorylation of the ß1 subunit is associated with the nuclear redistribution of AMPK (19). This has not yet been studied in human skeletal muscle or in AMPK complexes containing the ß2 subunit. Doing so could provide specific pharmacological targets for the treatment and management of insulin resistance and type 2 diabetes, given that AMPK appears to regulate many of the positive chronic adaptations to exercise via altered expression of various metabolic genes. An overview of recent studies suggests that AMPK might regulate gene expression by controlling the activity of various transcriptional regulators. Activation of AMPK has been associated with inactivation of the carbohydrate response element binding protein (20) and p300 transcriptional coactivator (21). Furthermore, AMPK activation increases myocyte enhancer factor 2 (MEF2 [22,23]) and nuclear respiratory factor 1 (NRF-1 [24]) DNA binding. MEF2 is a transcription factor that is required for GLUT-4 gene expression (25), while NRF-1 is thought to be a transcriptional activator of mitochondrial biogenesis (24). It has also been speculated that AMPK itself could participate as part of a transcriptional regulatory complex involved in DNA binding (21); however, there are no data to support this hypothesis at present.

In conclusion, the results from the present study demonstrate that an acute bout of exercise increases skeletal muscle nuclear AMPK {alpha}2 content. The nuclear translocation of AMPK describes a potential mechanism by which AMPK mediates the effects of exercise on the skeletal muscle gene and protein expression. Elucidating the underlying molecular mechanisms mediating AMPK nuclear translocation might be important for the treatment and management of insulin resistance and type 2 diabetes.


   ACKNOWLEDGMENTS
 
We would like to thank Robyn Murphy for her expert assistance in RT-PCR and in the development of the nuclear extraction technique. We also thank David Stapleton for assistance with the same technique, Janelle Mollica for designing the AMPK {alpha}2 PCR primers, and Adam Rose for assistance with the exercise trials.


   FOOTNOTES
 
Address correspondence to Prof. Mark Hargreaves, School of Health Sciences, Deakin University, 221 Burwood Highway, Burwood VIC 3125, Australia. E-mail: mharg{at}deakin.edu.au.

Received for publication 14 July 2002 and accepted in revised form 2 January 2003.

AICAR, 5-aminoimidazole-4-carboxamide ribonucleoside; AMPK, AMP-activated protein kinase; CreaT, creatine transporter; DTT, dithiothreitol; H1, histone 1; HKII, hexokinase II; L-PK, liver-type pyruvate kinase; MEF2, myocyte enhancer factor 2; NRF-1, nuclear respiratory factor 1.


   REFERENCES
TOP
 ABSTRACT
 RESEARCH DESIGN AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Henriksen EJ: Effects of acute exercise and exercise training on insulin resistance. J Appl Physiol 93:788 –796,2002[Abstract/Free Full Text]
  2. Kemp BE, Mitchelhill K, Stapleton D, Michell B, Chen ZP, Witters L: Dealing with the energy demand: the AMP-activated protein kinase (Review Article). Trends Biochem Sci 24:22 –25,1999[Medline]
  3. Fujii N, Hayashi T, Hirshman M, Smith J, Habinowski S, Kaijser L, Mu J, Ljungqvist O, Birnbaum M, Witters L, Thorell A, Goodyear LJ: Exercise induces isoform-specific increase in 5' AMP-activated protein kinase activity in human skeletal muscle. Biochem Biophys Res Comm 273:1150 –1155,2000[Medline]
  4. Musi N, Fujii N, Hirshman M, Thorell A, Goodyear LJ: AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise. Diabetes 50:921 –927,2001[Abstract/Free Full Text]
  5. Buhl ES, Jessen N, Pold R, Ledet T, Flyvbjerg A, Pedersen SB, Pedersen O, Schmitz O, Lund S: Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome. Diabetes 51:2199 –2206,2002[Abstract/Free Full Text]
  6. Holmes B, Kurth-Kraczek E, Winder W: Chronic activation of 5' AMP-activated protein kinase increases GLUT4, hexokinase, and glycogen in muscle. J Appl Physiol 87:1990 –1995,1999[Abstract/Free Full Text]
  7. Winder W, Holmes B, Rubink D, Jensen E, Chen M, Holloszy J: Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle. J Appl Physiol 88:2219 –2226,2000[Abstract/Free Full Text]
  8. Lo WS, Duggan L, Tolga NC, Emre, Belotserkovskya R, Lane WS, Shiekhattar R, Berger SL: Snf1: a histone kinase that works in concert with histone acetyltransferases Gcn5 to regulate transcription. Science 293:1142 –1146,2001[Abstract/Free Full Text]
  9. Salt I, Cellar JW, Hawley S, Prescott A, Woods A, Carling D, Hardie DG: AMP-activated protein kinase: greater AMP dependence, and preferential nuclear localisation, of complexes containing the {alpha}2 isoform. Biochem J 334:177 –187,2000
  10. da Silva Xavier G, Leclerc I, Salt I, Doiron B, Hardie D, Kahn A, Rutter G: Role of AMP-activated protein kinase in the regulation by glucose of islet beta cell gene expression. Proc Natl Acad Sci U S A 97:4023 –4028,2000[Abstract/Free Full Text]
  11. Kraniou Y, Cameron-Smith D, Misso M, Collier G, Hargreaves M: Effects of exercise on GLUT-4 and glycogenin gene expression in human skeletal muscle. J Appl Physiol 88:794 –796,2000[Abstract/Free Full Text]
  12. Evans W, Phinney S, Young V: Suction applied to a muscle biopsy maximises sample size. Med Sci Sports Exerc 14:101 –102,1986
  13. Blough E, Dineen B, Esser K: Extraction of nuclear proteins from striated muscle tissue. BioTechniques 26:202 –206,1999[Medline]
  14. Michell BJ, Stapleton D, Mitchelhill KI, House CM, Katsis F, Witters LA, Kemp BE: Isoform-specific purification and substrate specificity of the 5'-AMP–activated protein kinase. J Biol Chem 271:28445 –28450,1996[Abstract/Free Full Text]
  15. Koval JA, DeFronzo RA, O’Doherty RM, Printz R, Ardehali H, Granner DK, Mandarino LJ: Regulation of hexokinase II activity and expression in human muscle by moderate exercise. Am J Physiol 274:E304 –E308,1998
  16. Hood DA: Contractile activity-induced mitochondrial biogenesis in skeletal muscle. J Appl Physiol 90:1137 –1157,2001[Abstract/Free Full Text]
  17. Ojuka E, Nolte L, Holloszy J: Increased expression of GLUT-4 and hexokinase in rat epitrochlearis muscles exposed to AICAR in vitro. J Appl Physiol 88:1072 –1075,2000[Abstract/Free Full Text]
  18. Ojuka EO, Jones TE, Nolte LA, Chen M, Wamhoff BR, Sturek M, Holloszy JO: Regulation of GLUT4 biogenesis in muscle: evidence for involvement of AMPK and Ca2+. Am J Physiol 282:E1008 –E1013,2002[Abstract/Free Full Text]
  19. Warden S, Richardson C, O’Donnell J, Stapleton D, Kemp B, Witters L: Post-translational modifications to the beta-1 subunit of the AMP-activated protein kinase affect enzyme activity and cellular localization. Biochemistry 354:275 –283,2001
  20. Kawaguchi T, Osatomi K, Yamashita H, Kabashima T, Uyeda K: Mechanism for fatty acid "sparing" effect on glucose-induced transcription: regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase. J Biol Chem 277:3829 –3835,2002[Abstract/Free Full Text]
  21. Yang W, Hong Y, Shen X, Frankowski C, Camp H, Leff T: Regulation of transcription by AMP-activated protein kinase. J Biol Chem 276:38341 –38344,2001[Abstract/Free Full Text]
  22. Zheng D, MacLean P, Pohnert S, Knight J, Olson A, Winder W, Dohm G: Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase. J Appl Physiol 91:1073 –1083,2001[Abstract/Free Full Text]
  23. Song XM, Fiedler M, Galuska D, Ryder JW, Fernstrom M, Chibalin AV, Wallberg-Henriksson H, Zierath JR: 5-Aminoimidazole-4-carboxamide ribonucleoside treatment improves glucose homeostasis in insulin-resistant diabetic (ob/ob) mice. Diabetologia 45:56 –65,2002[Medline]
  24. Bergeron R, Ren JM, Cadman KS, Moore IK, Perret P, Pypaert M, Young LH, Semenkovich CF, Shulman GI: Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis. Am J Physiol 281:E1340 –E1346,2001[Abstract/Free Full Text]
  25. Mora S, Pessin JE: The MEF2A isoform is required for striated muscle-specific expression of the insulin-responsive GLUT4 glucose transporter. J Biol Chem 275:16323 –16328,2001[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 DiabetesHome page
S. L. McGee, B. J.W. van Denderen, K. F. Howlett, J. Mollica, J. D. Schertzer, B. E. Kemp, and M. Hargreaves
AMP-Activated Protein Kinase Regulates GLUT4 Transcription by Phosphorylating Histone Deacetylase 5
Diabetes, April 1, 2008; 57(4): 860 - 867.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. T. Putman, K. J. B. Martins, M. E. Gallo, G. D. Lopaschuk, J. A. Pearcey, I. M. MacLean, R. J. Saranchuk, and D. Pette
{alpha}-Catalytic subunits of 5'AMP-activated protein kinase display fiber-specific expression and are upregulated by chronic low-frequency stimulation in rat muscle
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1325 - R1334.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
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]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. Li, D. L. Coven, E. J. Miller, X. Hu, M. E. Young, D. Carling, A. J. Sinusas, and L. H. Young
Activation of AMPK {alpha}- and {gamma}-isoform complexes in the intact ischemic rat heart
Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1927 - H1934.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. Lopez-Soriano, C. Chiellini, M. Maffei, P. A. Grimaldi, and J. M. Argiles
Roles of Skeletal Muscle and Peroxisome Proliferator-Activated Receptors in the Development and Treatment of Obesity
Endocr. Rev., May 1, 2006; 27(3): 318 - 329.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
T. Toyoda, S. Tanaka, K. Ebihara, H. Masuzaki, K. Hosoda, K. Sato, T. Fushiki, K. Nakao, and T. Hayashi
Low-intensity contraction activates the {alpha}1-isoform of 5'-AMP-activated protein kinase in rat skeletal muscle
Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E583 - E590.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. Wilson, M. Hargreaves, and K. F. Howlett
Exercise does not alter subcellular localization, but increases phosphorylation of insulin-signaling proteins in human skeletal muscle
Am J Physiol Endocrinol Metab, February 1, 2006; 290(2): E341 - E346.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. E. Civitarese, M. K. C. Hesselink, A. P. Russell, E. Ravussin, and P. Schrauwen
Glucose ingestion during exercise blunts exercise-induced gene expression of skeletal muscle fat oxidative genes
Am J Physiol Endocrinol Metab, December 1, 2005; 289(6): E1023 - E1029.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
R. Li, M. Chase, S.-K. Jung, P. J. S. Smith, and M. R. Loeken
Hypoxic stress in diabetic pregnancy contributes to impaired embryo gene expression and defective development by inducing oxidative stress
Am J Physiol Endocrinol Metab, October 1, 2005; 289(4): E591 - E599.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
T. Toyoda, T. Hayashi, L. Miyamoto, S. Yonemitsu, M. Nakano, S. Tanaka, K. Ebihara, H. Masuzaki, K. Hosoda, G. Inoue, et al.
Possible involvement of the {alpha}1 isoform of 5'AMP-activated protein kinase in oxidative stress-stimulated glucose transport in skeletal muscle
Am J Physiol Endocrinol Metab, July 1, 2004; 287(1): E166 - E173.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
S. L. McGee and M. Hargreaves
Exercise and Myocyte Enhancer Factor 2 Regulation in Human Skeletal Muscle
Diabetes, May 1, 2004; 53(5): 1208 - 1214.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. Frosig, S. B. Jorgensen, D. G. Hardie, E. A. Richter, and J. F. P. Wojtaszewski
5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle
Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E411 - E417.
[Abstract] [Full Text]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McGee, S. L.
Right arrow Articles by Hargreaves, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McGee, S. L.
Right arrow Articles by Hargreaves, M.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum