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Am J Physiol Endocrinol Metab 290: E405-E408, 2006. First published October 11, 2005; doi:10.1152/ajpendo.00385.2005
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Energy state of the liver during short-term and exhaustive exercise in C57BL/6J mice

Raul C. Camacho, E. Patrick Donahue, Freyja D. James, Eric D. Berglund, and David H. Wasserman

Department of Molecular Physiology and Biophysics and Mouse Metabolic Phenotyping Center, Vanderbilt University School of Medicine, Nashville, Tennessee

Submitted 17 August 2005 ; accepted in final form 10 October 2005


   ABSTRACT
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 ABSTRACT
RESEARCH DESIGN AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
A portal venous 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion that results in hepatic 5-aminoimidazole-4-carboxamide-1-beta-D-ribosyl-5-monophosphate (ZMP) concentrations of ~4 µmol/g liver increases hepatic glycogenolysis and glucose output. ZMP is an AMP analog that mimics the regulatory actions of this nucleotide. The aim of this study was to measure hepatic AMP concentrations in response to increasing energy requirements to test the hypothesis that AMP achieves concentrations during exercise, consistent with a role in stimulation of hepatic glucose metabolism. Male C57BL/6J mice (27.4 ± 0.4 g) were subjected to 35 min of rest [sedentary (SED), n = 8], underwent short-term (ST, 35 min) moderate (20 m/min, 5% grade) exercise (n = 8), or underwent treadmill exercise under similar conditions but until exhaustion (EXH, n = 8). Hepatic AMP concentrations were 0.82 ± 0.05, 1.17 ± 0.11, and 2.52 ± 0.16 µmol/g liver in SED, ST, and EXH mice, respectively (P < 0.05). Hepatic energy charge was 0.66 ± 0.01, 0.58 ± 0.02, and 0.33 ± 0.22 in SED, ST, and EXH mice, respectively (P < 0.05). Hepatic glycogen was 11.6 ± 1.0, 8.8 ± 2.2, and 0.0 ± 0.1 mg/g liver in SED, ST, and EXH mice, respectively (P < 0.05). Hepatic AMPK (Thr172) phosphorylation was 1.00 ± 0.14, 1.96 ± 0.16, and 7.44 ± 0.63 arbitrary units in SED, ST, and EXH mice, respectively (P < 0.05). Thus exercise increases hepatic AMP concentrations. These data suggest that the liver is highly sensitive to metabolic demands, as evidenced by dramatic changes in cellular energy indicators (AMP) and sensors thereof (AMP-activated protein kinase). In conclusion, AMP is sensitively regulated, consistent with it having an important role in hepatic metabolism.

adenosine 5'-monophosphate; adenosine 5'-monophosphate-activated protein kinase; glycogen

ALMOST ALL CELLULAR PROCESSES are coupled to ATP breakdown, giving critical importance to the pathways that maintain appropriate ratios of AMP and ATP. It is not surprising that the cell has evolved sensitive mechanisms to detect, regulate, and compensate for changes in their levels. AMP-activated protein kinase (AMPK) is one such mechanism that acts to prevent deficits in energy metabolism during metabolic stresses, including exercise (9, 10, 23, 31, 33). AMP is well known to regulate, in addition to AMPK, other enzyme reactions that act to preserve cellular energy charge, including both liver (13, 14) and muscle (26) glycogen phosphorylase and fructose-1,6-bisphosphatase (22). It was recently shown that the intraportal infusion (1 mg·kg–1·min–1) of the purine nucleotide precursor 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) potently stimulates the breakdown of liver glycogen (5, 6, 24). Two aspects of this work were particularly noteworthy. First, AICAR-induced hepatic glycogen breakdown is AMPK independent because it occurs in the presence of marked hyperinsulinemia that suppresses the activation of AMPK (5). Second, the AICAR infusion was considerably less than previously used in vivo, creating hepatic 5-aminoimidazole-4-carboxamide-1-beta-D-ribosyl-5-monophospate (ZMP, an AMP analog) concentrations of ~4 µmol/g liver. This concentration of ZMP is comparable to AMP concentrations that stimulate purified glycogen phosphorylase (14, 21, 27).

It is clear from the discussion above that AICAR at low doses increases hepatic ZMP concentrations and glycogen breakdown. It is unknown, however, whether hepatic AMP and ATP concentrations are affected by physiological conditions, such as exercise, and might therefore be significant physiological regulators of hepatic glycogen metabolism. The hypothesis tested in the present study was that the metabolic demands on the liver during muscular work result in an AMP signal of sufficient magnitude to stimulate hepatic glycogen mobilization, and is therefore an important physiological regulator of the process.


   RESEARCH DESIGN AND METHODS
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Animals. Procedures were approved by the Vanderbilt University Animal Care and Use Committee. Twenty-four male C57BL/6J (27.4 ± 0.4 g) mice were purchased from Jackson Laboratories. Mice were housed in a temperature-controlled environment with a 12:12-h light-dark cycle and fed a standard ad libitum diet. Mice were studied at 10 wk of age.

Experiments. Mice were fasted for 5 h before experiments. For exercise experiments, mice were acclimated to a treadmill running with a single, 10-min bout of exercise (20 m/min, 5% grade). One group of mice remained sedentary (SED) within the treadmill for 35 min (n = 8). A second group of mice underwent short-term (ST, 35 min), moderate (20 m/min, 5% grade) exercise (n = 8). A third group of mice exercised under similar treadmill conditions until exhaustion (EXH, n = 8; time to exhaustion was 84 ± 12 min). Mice were defined as exhausted if they remained on the shock grid placed at the end of the treadmill (1.5 mA, 200-ms pulses, 4 Hz) for five continuous seconds. Mice were killed by cervical dislocation, and livers and gastrocnemius muscles were excised (within 30 and 45 s, respectively), freeze-clamped in liquid nitrogen, and stored at –70°C until future analysis.

Tissue analyses. Tissue adenine nucleotide concentrations were determined from liver and muscle samples homogenized in 0.4 M perchloric acid/0.5 mM EGTA and neutralized with 0.5 M potassium carbonate (pH 6.8). HPLC analysis and UV detection were performed to assess nucleotide levels, as described previously (1, 34).

Approximately 50 mg of liver samples were homogenized in a solution containing 10% glycerol, 20 mM Na-pyrophospate, 150 mM NaCl, 50 mM HEPES (pH 7.5), 1% NP-40, 20 mM beta-glycerophosphate, 10 mM NaF, 2 mM EDTA (pH 8.0), 2 mM PMSF, 1 mM CaCl2, 1 mM MgCl2, 10 µg/ml aprotinin, 10 µg/ml leupeptin, 2 mM Na2VO3, and 3 mM benzamide. Homogenized samples were assayed for protein concentration using a Pierce bicinchoninic acid protein assay kit (Rockford, IL). Thirty micrograms of protein were run on an SDS-PAGE gel and transferred to a polyvinylidene difluoride membrane. Equal protein loading was confirmed by staining membranes with 0.1% Ponceau S in 5% acetic acid and rinsing with deionized water. Membranes were treated with rabbit {alpha}-phospho-AMPK (Thr172; Cell Signaling, Beverly, MA) and then incubated with {alpha}-rabbit-horseradish peroxidase (Promega, Madison, WI). Chemiluminescence was detected with a WesternBreeze kit from Invitrogen (Carlsbad, CA). Densitometry was performed using Scion Image (Frederick, MD) software. Liver glycogen was determined as described previously (6).

Calculations. Energy charge was calculated by the following equation: [ATP + ADP]/[ATP + ADP + AMP], where AMP, ADP, and ATP are the respective tissue concentrations (2).

Statistical analysis. Statistical comparisons between groups were made using one-way ANOVA. These were followed by the Fisher least significant difference test for post hoc comparisons. Statistics are reported in figures. Data are presented as means ± SE. Statistical significance was defined as P < 0.05.


   RESULTS
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 ABSTRACT
 RESEARCH DESIGN AND METHODS
 RESULTS
DISCUSSION
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Tissue adenine nucleotides and energy charge. Liver AMP and ATP concentrations were significantly increased (0.82 ± 0.05 to 1.17 ± 0.11 µmol/g liver) and decreased (2.42 ± 0.09 to 1.94 ± 0.14 µmol/g liver), respectively, in ST vs. SED (Fig. 1, P < 0.05). Liver AMP and ATP concentrations were further increased (2.52 ± 0.16 µmol/g liver) and decreased (0.78 ± 0.10 µmol/g liver), respectively, in EXH (P < 0.05, compared with ST and SED). Liver ADP concentrations were not affected by exercise. Five mice were killed by cervical dislocation, and the time between death and freeze-clamping was varied. Liver AMP, ADP, and ATP were not significantly different at 30, 60, 90, or 150 s after cervical dislocation (data not shown). Gastrocnemius AMP concentrations were significantly increased (0.08 ± 0.01 and 0.11 ± 0.02 vs. 0.04 ± 0.01 µmol/g muscle) in ST and EXH vs. SED (P < 0.05; Fig. 2). Neither gastrocnemius ADP nor ATP concentrations were affected by exercise. Hepatic energy charge was significantly decreased (0.66 ± 0.01 to 0.58 ± 0.02) in ST vs. SED (P < 0.05; Fig. 3). Hepatic energy charge was further decreased (P < 0.05) in EXH (0.33 ± 0.02). Energy charge was unaffected by exercise in gastrocnemius.


Figure 1
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  		Fig. 1. Hepatic adenine nucleotide concentrations in male C57BL/6J mice subjected to 35 min of rest [sedentary (SED); open bars], short-term (ST) moderate exercise (gray bars), and treadmill exercise under similar conditions, but until exhaustion (EXH; filled bars). Data are means ± SE. *Significantly different from SED (P < 0.05) mice; {dagger}significantly different from SED and ST (P < 0.05) mice.

 

Figure 2
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  		Fig. 2. Gastrocnemius adenine nucleotide concentrations in SED (open bars), ST (gray bars), and EXH (filled bars) mice. Data are means ± SE. *Significantly different from SED (P < 0.05).

 

Figure 3
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  		Fig. 3. Energy charge in liver and gastrocnemius in SED (open bars), ST (gray bars), and EXH (filled bars) mice. Data are means ± SE. *Significantly different from SED (P < 0.05); {dagger}significantly different from SED and ST (P < 0.05).

 
Liver AMPK phosphorylation and glycogen. Liver AMPK (Thr172) phosphorylation was significantly increased in ST vs. SED (P < 0.05; Fig. 4A). Liver AMPK (Thr172) phosphorylation was further increased in EXH (P < 0.05). Liver glycogen was significantly decreased in ST vs. SED (P < 0.05; Fig. 4B). Liver glycogen was essentially depleted in EXH.


Figure 4
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  		Fig. 4. Hepatic AMPK Thr172 phosphorylation (A) and glycogen (B) in SED (open bars), ST (gray bars), and EXH (filled bars) mice. Data are means ± SE. *Significantly different from SED (P < 0.05); {dagger}significantly different from SED and ST (P < 0.05).

 

   DISCUSSION
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 ABSTRACT
 RESEARCH DESIGN AND METHODS
 RESULTS
 DISCUSSION
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The results of the present study show that 35 min of moderate exercise results in a deficit in energy status of the liver as defined by increased hepatic AMP concentrations and decreased ATP concentrations. When mice were exercised to exhaustion, hepatic AMP and ATP concentrations were significantly increased and decreased further. At the same time, changes in muscle adenine nucleotides were considerably less or undetectable. A comparison of changes in liver and muscle adenine nucleotide concentrations shows that the energy status of the liver is much more sensitive to changes in metabolic demand than that of the muscle.

Hepatic AMP concentrations in EXH were similar to hepatic concentrations of ZMP obtained in the dog that received an intraportal AICAR infusion. These hepatic ZMP levels markedly stimulate glycogen breakdown and glucose release from the liver despite basal glucagon, hyperinsulinemia, and euglycemia (6). Subsequent studies (5) have shown that pharmacological insulin levels prevent ZMP-induced AMPK activation but not glycogen breakdown. AMP and ZMP have been shown (14, 21, 27) to activate glycogen phosphorylase directly via allosteric mechanisms. AMPK phosphorylates (8) and inactivates glycogen synthase as well (32). The AMP values attained with ST (1.7 mM) and exhaustive (3.6 mM) exercise are within the range of AMP/ZMP concentrations (0.05–5 mM) shown to allosterically activate glycogen phosphorylase (14, 21, 27).

The body aggressively protects arterial glucose concentrations from falling during exercise despite increased muscle glucose uptake by stimulating the release of glucose from the liver (4, 29, 30). The increases in endogenous glucose production in the dog during exercise (4) and a 1 mg·kg–1·min–1 intraportal AICAR infusion (6) are similar. Clearly, one must be cautious in comparing the species. However, it is interesting to note that the levels in ZMP that cause an increase in glucose production are similar to AMP levels that occur during exercise, albeit in the mouse.

Hepatic AMP concentrations were increased 1.4- and 2.1-fold in ST and EXH mice, respectively. A novel finding of these studies is that hepatic AMPK (Thr172) phosphorylation was increased 2- and 6.4-fold in ST and EXH mice, respectively (Fig. 4). These findings are consistent with earlier studies (9, 23) showing that exercise significantly increased AMPK activity (phosphorylation was not measured). The difference in the increases in AMP concentrations and AMPK phosphorylation reflect AMP’s effects on multiple enzymes in regulation of AMPK phosphorylation (12, 15, 16, 20). AMPK is activated allosterically by an increase in AMP concentration (7, 15), as well as covalently by phosphorylation of a threonine residue (Thr172) by an upstream kinase, AMPKK/LKB1 (15, 20). Covalent modification is also dependent on AMP in that 1) binding of AMP to AMPK makes it a better substrate for AMPKK/LKB1 (16), and 2) binding of AMP to AMPK makes it a poor substrate for protein phosphatases (12). The sensitivity of the liver in detecting energy status is exemplified by exaggerated changes in AMPK phosphorylation compared with changes in AMP.

Recent work has also shown a role for increased cAMP concentrations, which are increased during exercise due to rises in both glucagon and catecholamines, in the regulation of AMPK (Thr172) phosphorylation. Kimball et al. (19) showed that activation of cAMP-dependent protein kinase (PKA) by glucagon is associated with the phosphorylation of LKB1 as well as phosphorylation of AMPK on Thr172 in rat liver. The link between PKA and AMPK is also supported by a study in adipocytes that shows that activation of PKA using forskolin, isoproteronol, or cAMP analogs results in AMPK (Thr172) phosphorylation (35). Finally, cAMP-specific phosphodiesterases have been shown to be expressed in liver and activated by hormones that increase cAMP concentrations (18, 28), which would in turn increase AMP and AMPK phosphorylation. Future studies will be informative in testing the link between glucagon action and hepatic AMP concentrations.

Short-term and exhaustive exercise modestly, yet significantly, increased gastrocnemius AMP concentrations (Fig. 2) to similar concentrations seen in electrically stimulated gastrocnemius (17). However, in contrast to the liver, gastrocnemius ATP concentrations were rigorously protected from changing with energy requirement, as has been previously shown (3, 11, 33). The protection of muscle ATP levels results from the presence of the creatine-phosphate/kinase system and increased mitochondrial respiratory capacity (25).

Results from these studies (11, 17, 31) and ones performed previously show that exercise increases muscle AMP concentrations. This increase has been proposed to have important regulatory ramifications, activating AMPK and increasing translocation of glucose transporter 4. The intriguing novel findings of the present study are that AMP concentrations increase in the liver, as well during exercise, corresponding with increasing energy requirements. Remarkably, the increase in hepatic AMP during exercise dwarfs that seen in the working muscle. The changes in the cellular energy indicator, AMP (as well as ATP), are reflected by changes in energy charge and phosphorylation of the cellular energy sensor, AMPK. In conclusion, the data are consistent with the concept that the liver is highly sensitive (even more so than muscle) to changes in metabolic demands and that adenine nucleotides are candidate-signaling molecules involved in hepatic glucose production during a condition such as exercise.


   GRANTS
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 ABSTRACT
 RESEARCH DESIGN AND METHODS
 RESULTS
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This work was funded by National Institute of Diabetes and Digestive and Kidney Diseases Grant No. RO1 DK-50277 and, to the Mouse Metabolic Phenotyping Center, U24 DK-59637.


   FOOTNOTES
 

Address for reprint requests and other correspondence: R. Camacho, Dept. of Medicine, Division of Endocrinology, Belfer 701, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461 (e-mail:rcamacho{at}aecom.yu.edu)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


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  1. Ally A and Park G. Rapid determination of creatine, phosphocreatine, purine bases and nucleotides (ATP, ADP, AMP, GTP, GDP) in heart biopsies by gradient ion-pair reversed-phase liquid chromatography. J Chromatogr 575: 19–27, 1992.[ISI][Medline]
  2. Atkinson DE and Walton GM. Adenosine triphosphate conservation in metabolic regulation. Rat liver citrate cleavage enzyme. J Biol Chem 242: 3239–3241, 1967.[Abstract/Free Full Text]
  3. Baldwin J, Snow RJ, Gibala MJ, Garnham A, Howarth K, and Febbraio MA. Glycogen availability does not affect the TCA cycle or TAN pools during prolonged, fatiguing exercise. J Appl Physiol 94: 2181–2187, 2003.[Abstract/Free Full Text]
  4. Berger CM, Sharis PJ, Bracy DP, Lacy DB, and Wasserman DH. Sensitivity of exercise-induced increase in hepatic glucose production to glucose supply and demand. Am J Physiol Endocrinol Metab 267: E411–E421, 1994.[Abstract/Free Full Text]
  5. Camacho RC, James FD, Donahue EP, and Wasserman DH. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside renders glucose output by the liver of the dog insensitive to a pharmacological increment in insulin. Am J Physiol Endocrinol Metab 289, E1039–E1043, 2005.[Abstract/Free Full Text]
  6. Camacho RC, Pencek RR, James F, Lacy DB, and Wasserman DH. Portal venous 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside overcomes hyperinsulinemic suppression of endogenous glucose output. Diabetes 54: 373–382, 2005.[Abstract/Free Full Text]
  7. Carling D, Clarke PR, Zammit VA, and Hardie DG. Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities. Eur J Biochem 186: 129–136, 1989.[ISI][Medline]
  8. Carling D and Hardie DG. The substrate and sequence specificity of the AMP-activated protein kinase. Phosphorylation of glycogen synthase and phosphorylase kinase. Biochim Biophys Acta 1012: 81–86, 1989.[Medline]
  9. Carlson CI and Winder WW. Liver AMPK-activated protein kinase and acetyl-CoA carboxylase during and after exercise. J Appl Physiol 86: 669–674, 1999.[Abstract/Free Full Text]
  10. Chen ZP, McConell GK, Michell BJ, Snow RJ, Canny BJ, and Kemp BE. AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation. Am J Physiol Endocrinol Metab 279: E1202–E1206, 2000.[Abstract/Free Full Text]
  11. Chen ZP, Stephens TJ, Murthy S, Canny BJ, Hargreaves M, Witters LA, Kemp BE, and McConell GK. Effect of exercise intensity on skeletal muscle AMPK signaling in humans. Diabetes 52: 2205–2212, 2003.[Abstract/Free Full Text]
  12. Davies SP, Helps NR, Cohen PT, and Hardie DG. 5'-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC. FEBS Lett 377: 421–425, 1995.[CrossRef][ISI][Medline]
  13. Ercan N, Gannon MC, and Nuttall FQ. Allosteric regulation of liver phosphorylase a: revisited under approximated physiological conditions. Arch Biochem Biophys 328: 255–264, 1996.[CrossRef][ISI][Medline]
  14. Ercan-Fang N, Gannon MC, Rath VL, Treadway JL, Taylor MR, and Nuttall FQ. Integrated effects of multiple modulators on human liver glycogen phosphorylase a. Am J Physiol Endocrinol Metab 283: E29–E37, 2002.[Abstract/Free Full Text]
  15. Hawley SA, Davison M, Woods A, Davies SP, Beri RK, Carling D, and Hardie DG. Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. J Biol Chem 271: 27879–27887, 1996.[Abstract/Free Full Text]
  16. Hawley SA, Selbert MA, Goldstein EG, Edelman AM, Carling D, and Hardie DG. 5'-AMP activates the AMP-activated protein kinase cascade, and Ca2+/calmodulin activates the calmodulin-dependent protein kinase I cascade, via three independent mechanisms. J Biol Chem 270: 27186–27191, 1995.[Abstract/Free Full Text]
  17. Hutber CA, Hardie DG, and Winder WW. Electrical stimulation inactivates muscle acetyl-CoA carboxylase and increases AMP-activated protein kinase. Am J Physiol Endocrinol Metab 272: E262–E266, 1997.[Abstract/Free Full Text]
  18. Kilgour E, Anderson NG, and Houslay MD. Activation and phosphorylation of the ’dense-vesicle’ high-affinity cyclic AMP phosphodiesterase by cyclic AMP-dependent protein kinase. Biochem J 260: 27–36, 1989.[ISI][Medline]
  19. Kimball SR, Siegfried BA, and Jefferson LS. Glucagon represses signaling through the mammalian target of rapamycin in rat liver by activating AMP-activated protein kinase. J Biol Chem 279: 54103–54109, 2004.[Abstract/Free Full Text]
  20. Lizcano JM, Goransson O, Toth R, Deak M, Morrice NA, Boudeau J, Hawley SA, Udd L, Makela TP, Hardie DG, and Alessi DR. LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J 23: 833–843, 2004.[CrossRef][ISI][Medline]
  21. Longnus SL, Wambolt RB, Parsons HL, Brownsey RW, and Allard MF. 5-Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR) stimulates myocardial glycogenolysis by allosteric mechanisms. Am J Physiol Regul Integr Comp Physiol 284: R936–R944, 2003.[Abstract/Free Full Text]
  22. Nelson SW, Honzatko RB, and Fromm HJ. Hybrid tetramers of porcine liver fructose-1,6-bisphosphatase reveal multiple pathways of allosteric inhibition. J Biol Chem 277: 15539–15545, 2002.[Abstract/Free Full Text]
  23. Park H, Kaushik VK, Constant S, Prentki M, Przybytkowski E, Ruderman NB, and Saha AK. Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in rat tissues in response to exercise. J Biol Chem 277: 32571–32577, 2002.[Abstract/Free Full Text]
  24. Pencek RR, Shearer J, Camacho RC, James FD, Lacy DB, Fueger PT, and Wasserman DH. 5'-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside causes acute hepatic insulin resistance in vivo. Diabetes 54: 355–360, 2005.[Abstract/Free Full Text]
  25. Robergs RA, Ghiasvand F, and Parker D. Biochemistry of exercise-induced metabolic acidosis. Am J Physiol Regul Integr Comp Physiol 287: R502–R516, 2004.[Abstract/Free Full Text]
  26. Rush JW and Spriet LL. Skeletal muscle glycogen phosphorylase a kinetics: effects of adenine nucleotides and caffeine. J Appl Physiol 91: 2071–2078, 2001.[Abstract/Free Full Text]
  27. Shang J and Lehrman MA. Activation of glycogen phosphorylase with 5-aminoimidazole-4-carboxamide riboside (AICAR). Assessment of glycogen as a precursor of mannosyl residues in glycoconjugates. J Biol Chem 279: 12076–12080, 2004.[Abstract/Free Full Text]
  28. Shepherd M, McSorley T, Olsen AE, Johnston LA, Thomson NC, Baillie GS, Houslay MD, and Bolger GB. Molecular cloning and subcellular distribution of the novel PDE4B4 cAMP-specific phosphodiesterase isoform. Biochem J 370: 429–438, 2003.[CrossRef][ISI][Medline]
  29. Wasserman DH. Control of glucose fluxes during exercise in the postabsorptive state. In: Annual Review of Physiology. Palo Alto, CA: Annual Reviews, 1995, p. 191–218.
  30. Wasserman DH and Cherrington AD. Hepatic fuel metabolism during exercise: role and regulation. Am J Physiol Endocrinol Metab 260: E811–E824, 1991.[Abstract/Free Full Text]
  31. Winder WW and Hardie DG. Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am J Physiol Endocrinol Metab 270: E299–E304, 1996.[Abstract/Free Full Text]
  32. Wojtaszewski JF, Jorgensen SB, Hellsten Y, Hardie DG, and Richter EA. Glycogen-dependent effects of 5-aminoimidazole-4-carboxamide (AICA)-riboside on AMP-activated protein kinase and glycogen synthase activities in rat skeletal muscle. Diabetes 51: 284–292, 2002.[Abstract/Free Full Text]
  33. Wojtaszewski JF, MacDonald C, Nielsen JN, Hellsten Y, Hardie DG, Kemp BE, Kiens B, and Richter EA. Regulation of 5'AMP-activated protein kinase activity and substrate utilization in exercising human skeletal muscle. Am J Physiol Endocrinol Metab 284: E813–E822, 2003.[Abstract/Free Full Text]
  34. Wynants J and Van Belle H. Single-run high-performance liquid chromatography of nucleotides, nucleosides, and major purine bases and its application to different tissue extracts. Anal Biochem 144: 258–266, 1985.[CrossRef][ISI][Medline]
  35. Yin W, Mu J, and Birnbaum MJ. Role of AMP-activated protein kinase in cyclic AMP-dependent lipolysis In 3T3-L1 adipocytes. J Biol Chem 278: 43074–43080, 2003.[Abstract/Free Full Text]



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