Regulation of exercise-induced fiber type transformation, mitochondrial biogenesis, and angiogenesis in skeletal muscle

Journal of Applied Physiology

Volumn 110, Issue 1, 2011, Pages 264-274

  Yan, Zhen ^a   Okutsu, Mitsuharu ^a   Akhtar, Yasir N ^a   Lira, Vitor A ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

Author keywords

Angiogenesis; Endurance exercise; Fiber type transformation; Mitochondrial biogenesis; Skeletal muscle adaptation

Indexed keywords

ADAPTATION; ANGIOGENESIS; ANIMAL; EXERCISE; HUMAN; MUSCLE CONTRACTION; MUSCLE MITOCHONDRION; PHYSIOLOGY; REVIEW; SKELETAL MUSCLE;

ADAPTATION, PHYSIOLOGICAL; ANIMALS; HUMANS; MITOCHONDRIA, MUSCLE; MUSCLE CONTRACTION; MUSCLE FIBERS, SKELETAL; NEOVASCULARIZATION, PHYSIOLOGIC; PHYSICAL EXERTION;

EID: 79251479441     PISSN: 87507587     EISSN: 15221601     Source Type: Journal    
DOI: 10.1152/japplphysiol.00993.2010     Document Type: Review

References (198)

1. Adhihetty PJ, Uguccioni G, Leick L, Hidalgo J, Pilegaard H, Hood DA. The role of PGC-1α on mitochondrial function and apoptotic susceptibility in muscle. Am J Physiol Cell Physiol 297: C217-C225, 2009.
2. Akimoto T, Li P, Yan Z. Functional interaction of regulatory factors with the Pgc-1α promoter in response to exercise by in vivo imaging. Am J Physiol Cell Physiol 295: C288-C292, 2008.
3. Akimoto T, Pohnert S, Li P, Zhang M, Gumbs C, Rosenberg P, Williams R, Yan Z. Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway. J Biol Chem 280: 19587-19593, 2005.
4. Akimoto T, Ribar T, Williams R, Yan Z. Skeletal muscle adaptation in response to voluntary running in Ca2+/calmodulin-dependent protein kinase IV-deficient mice. Am J Physiol Cell Physiol 287: C1311-C1319, 2004.
5. Andersen P, Henriksson J. Training induced changes in the subgroups of human type II skeletal muscle fibres. Acta Physiol Scand 99: 123-125, 1977.
6. Andersen P, Saltin B. Maximal perfusion of skeletal muscle in man. J Physiol 366: 233-249, 1985.
7. Arany Z, Foo S, Ma Y, Ruas J, Bommi-Reddy A, Girnun G, Cooper M, Laznik D, Chinsomboon J, Rangwala S, Baek K, Rosenzweig A, Spiegelman B. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature 451: 1008-1012, 2008.
8. Baar K, Wende A, Jones T, Marison M, Nolte L, Chen M, Kelly D, Holloszy J. Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1. FASEB J 16: 1879-1886, 2002.
9. Balakrishnan VS, Rao M, Menon V, Gordon PL, Pilichowska M, Castaneda F, Castaneda-Sceppa C. Resistance training increases muscle mitochondrial biogenesis in patients with chronic kidney disease. Clin J Am Soc Nephrol 5: 996-1002, 2010.
10. Birot O, Koulmann N, Peinnequin A, Bigard X. Exercise-induced expression of vascular endothelial growth factor mRNA in rat skeletal muscle is dependent on fibre type. J Physiol 552: 213-221, 2003.
11. Booth FW, Baldwin KM. Muscle plasticity: energy demand and supply processes. In: Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, MD: Am. Physiol. Soc, 1996, sect. 12, chapt. 24, p. 1075-1123.
12. Breen E, Johnson E, Wagner H, Tseng H, Sung L, Wagner P. Angiogenic growth factor mRNA responses in muscle to a single bout of exercise. J Appl Physiol 81: 355-361, 1996.
13. Buller AJ, Eccles JC, Eccles RM. Interactions between motoneurone and muscles in respect of the characteristic speeds of their responses. J Physiol 150: 417-439, 1960.
14. Burgomaster KA, Howarth KR, Phillips SM, Rakobowchuk M, Macdonald MJ, McGee SL, Gibala MJ. Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans. J Physiol 586: 151-160, 2008.
15. Calabria E, Ciciliot S, Moretti I, Garcia M, Picard A, Dyar KA, Pallafacchina G, Tothova J, Schiaffino S, Murgia M. NFAT isoforms control activity-dependent muscle fiber type specification. Proc Natl Acad Sci USA 106: 13335-13340, 2009.
16. Calvo JA, Daniels TG, Wang X, Paul A, Lin J, Spiegelman BM, Stevenson SC, Rangwala SM. Muscle-specific expression of PPARgamma coactivator-1alpha improves exercise performance and increases peak oxygen uptake. J Appl Physiol 104: 1304-1312, 2008.
17. Canto C, Auwerx J. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol 20: 98-105, 2009.
18. + metabolism and SIRT1 activity. Nature 2009.
19. Canto C, Jiang LQ, Deshmukh AS, Mataki C, Coste A, Lagouge M, Zierath JR, Auwerx J. Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab 11: 213-219, 2010.
20. Cao W, Daniel KW, Robidoux J, Puigserver P, Medvedev AV, Bai X, Floering LM, Spiegelman BM, Collins S. p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol Cell Biol 24: 3057-3067, 2004.
21. Carrow RE, Brown RE, Van Huss WD. Fiber sizes and capillary to fiber ratios in skeletal muscle of exercised rats. Anat Rec 159: 33-39, 1967.
22. Centers for Disease Control and Prevention. Prevalence of physical inactivity during leisure time among overweight persons-1994. JAMA 275 905, 1996.
23. Chin E, Olson E, Richardson J, Yang Q, Humphries C, Shelton J, Wu H, Zhu W, Bassel-Duby R, Williams R. A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev 12: 2499-2509, 1998.
24. Chinsomboon J, Ruas J, Gupta RK, Thom R, Shoag J, Rowe GC, Sawada N, Raghuram S, Arany Z. The transcriptional coactivator PGC-1alpha mediates exercise-induced angiogenesis in skeletal muscle. Proc Natl Acad Sci USA 106: 21401-21406, 2009.
25. Clayton DA. Mitochondrial DNA replication: what we know. IUBMB Life 55: 213-217, 2003.
26. Clayton DA. Vertebrate mitochondrial DNA-a circle of surprises. Exp Cell Res 255: 4-9, 2000.
27. Close GL, Ashton T, Cable T, Doran D, Noyes C, McArdle F, MacLaren DP. Effects of dietary carbohydrate on delayed onset muscle soreness and reactive oxygen species after contraction induced muscle damage. Br J Sports Med 39: 948-953, 2005.
28. Costford SR, Bajpeyi S, Pasarica M, Albarado DC, Thomas SC, Xie H, Church T, Jubrias SA, Conley KE, Smith SR. Skeletal muscle NAMPT is Induced by Exercise in Humans. Am J Physiol Endocrinol Metab 298: E117-E126, 2010.
29. Cotter M, Hudlicka O, Vrbova G. Growth of capillaries during longterm activity in skeletal muscle. Bibl Anat 11: 395-398, 1973.
30. Coyle EF. Improved muscular efficiency displayed as Tour de France champion matures. J Appl Physiol 98: 2191-2196, 2005.
31. 2+ oscillations. Science 279: 227-230, 1998.
32. Dufour E, Larsson NG. Understanding aging: revealing order out of chaos. Biochim Biophys Acta 1658: 122-132, 2004.
33. Eddinger TJ, Moss RL. Mechanical properties of skinned single fibers of identified types from rat diaphragm. Am J Physiol Cell Physiol 253: C210-C218, 1987.
34. Ennion S, Sant'ana Pereira J, Sargeant AJ, Young A, Goldspink G. Characterization of human skeletal muscle fibres according to the myosin heavy chains they express. J Muscle Res Cell Motil 16: 35-43, 1995.
35. Figueiredo PA, Mota MP, Appell HJ, Duarte JA. The role of mitochondria in aging of skeletal muscle. Biogerontology 9: 67-84, 2008.
36. Fitzsimons D, Diffee G, Herrick R, Baldwin K. Effects of endurance exercise on isomyosin patterns in fast- and slow-twitch skeletal muscles. J Appl Physiol 68: 1950-1955, 1990.
37. Franklin BA, Wrisley D, Johnson S, Mitchell M, Rubenfire M. Chronic adaptations to physical conditioning in cardiac patients. Implications regarding exercise trainability. Clin Sports Med 3: 471-512, 1984.
38. Frey N, Frank D, Lippl S, Kuhn C, Kögler H, Barrientos T, Rohr C, Will R, Müller OJ, Weiler H, Bassel-Duby R, Katus HA, Olson EN. Calsarcin-2 deficiency increases exercise capacity in mice through calcineurin/ NFAT activation. J Clin Invest 118: 3598-3608, 2008.
39. Fujii N, Hayashi T, Hirshman M, Smith J, Habinowski S, Kaijser L, Mu J, Ljungqvist O, Birnbaum M, Witters L, Thorell A, Goodyear L. Exercise induces isoform-specific increase in 5′AMP-activated protein kinase activity in human skeletal muscle. Biochem Biophys Res Commun 273: 1150-1155, 2000.
40. Fulco M, Cen Y, Zhao P, Hoffman EP, McBurney MW, Sauve AA, Sartorelli V. Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev Cell 14: 661-673, 2008.
41. Garcia-Roves P, Huss J, Holloszy J. Role of calcineurin in exerciseinduced mitochondrial biogenesis. Am J Physiol Endocrinol Metab 290: E1172-E1179, 2006.
42. Garcia-Roves PM, Osler ME, Holmstrom MH, Zierath JR. Gain-offunction R225Q mutation in AMP-activated protein kinase gamma3 subunit increases mitochondrial biogenesis in glycolytic skeletal muscle. J Biol Chem 283: 35724-35734, 2008.
43. Geng T, Li P, Okutsu M, Yin X, Kwek J, Zhang M, Yan Z. PGC-1α plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle. Am J Physiol Cell Physiol 298: C572-C579, 2010.
44. Gibala M. Molecular responses to high-intensity interval exercise. Appl Physiol Nutr Metab 34: 428-432, 2009.
45. Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, Sastre J, Vina J. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr 87: 142-149, 2008.
46. Goodpaster BH, Katsiaras A, Kelley DE. Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity. Diabetes 52: 2191-2197, 2003.
47. Goodyear LJ, Chang PY, Sherwood DJ, Dufresne SD, Moller DE. Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways in rat skeletal muscle. Am J Physiol Endocrinol Metab 271: E403-E408, 1996.
48. Goto M, Terada S, Kato M, Katoh M, Yokozeki T, Tabata I, Shimokawa T. cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats. Biochem Biophys Res Commun 274: 350-354, 2000.
49. Green HJ, Thomson JA, Daub WD, Houston ME, Ranney DA. Fiber composition, fiber size and enzyme activities in vastus lateralis of elite athletes involved in high intensity exercise. Eur J Appl Physiol Occup Physiol 41: 109-117, 1979.
50. Gurd BJ, Yoshida Y, Lally J, Holloway GP, Bonen A. The deacetylase enzyme SIRT1 is not associated with oxidative capacity in rat heart and skeletal muscle and its overexpression reduces mitochondrial biogenesis. J Physiol 587: 1817-1828, 2009.
51. Gustafsson T, Puntschart A, Kaijser L, Jansson E, Sundberg CJ. Exercise-induced expression of angiogenesis-related transcription and growth factors in human skeletal muscle. Am J Physiol Heart Circ Physiol 276: H679-H685, 1999. (Pubitemid 29100638)
52. Gute D, Fraga C, Laughlin M, Amann J. Regional changes in capillary supply in skeletal muscle of high-intensity endurance-trained rats. J Appl Physiol 81: 619-626, 1996.
53. Gute D, Laughlin M, Amann J. Regional changes in capillary supply in skeletal muscle of interval-sprint and low-intensity, endurance-trained rats. Microcirculation 1: 183-193, 1994.
54. Hancock CR, Janssen E, Terjung RL. Contraction-mediated phosphorylation of AMPK is lower in skeletal muscle of adenylate kinasedeficient mice. J Appl Physiol 100: 406-413, 2006.
55. Handschin C, Chin S, Li P, Liu F, Maratos-Flier E, Lebrasseur N, Yan Z, Spiegelman B. Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals. J Biol Chem 282: 30014-30021, 2007.
56. Handschin C, Choi CS, Chin S, Kim S, Kawamori D, Kurpad AJ, Neubauer N, Hu J, Mootha VK, Kim YB, Kulkarni RN, Shulman GI, Spiegelman BM. Abnormal glucose homeostasis in skeletal musclespecific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk. J Clin Invest 117: 3463-3474, 2007.
57. Handschin C, Rhee J, Lin J, Tarr P, Spiegelman B. An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle. Proc Natl Acad Sci USA 100: 7111-7116, 2003.
58. Hardie DG. Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology 144: 5179-5183, 2003.
59. Hardie DG, Carling D. The AMP-activated protein kinase-fuel gauge of the mammalian cell? Eur J Biochem 246: 259-273, 1997.
60. Hashimoto T, Hussien R, Oommen S, Gohil K, Brooks GA. Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis. FASEB J 21: 2602-2612, 2007.
61. Henriksson J. Training induced adaptation of skeletal muscle and metabolism during submaximal exercise. J Physiol 270: 661-675, 1977. (Pubitemid 8170341)
62. Hickey M, Carey J, Azevedo J, Houmard J, Pories W, Israel R, Dohm G. Skeletal muscle fiber composition is related to adiposity and in vitro glucose transport rate in humans. Am J Physiol Endocrinol Metab 268: E453-E457, 1995.
63. Holloszy JO. Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. J Biol Chem 242: 2278-2282, 1967.
64. Holloszy JO, Booth FW. Biochemical adaptations to endurance exercise in muscle. Annu Rev Physiol 38: 273-291, 1976.
65. Hood DA. Contractile activity-induced mitochondrial biogenesis in skeletal muscle. J Appl Physiol 90: 1137-1157, 2001.
66. Hoppeler H, Luthi P, Claassen H, Weibel E, Howald H. The ultrastructure of the normal human skeletal muscle. A morphometric analysis on untrained men, women and well-trained orienteers. Pflügers Arch 344: 217-232, 1973.
67. Horton MJ, Brandon CA, Morris TJ, Braun TW, Yaw KM, Sciote JJ. Abundant expression of myosin heavy-chain IIB RNA in a subset of human masseter muscle fibres. Arch Oral Biol 46: 1039-1050, 2001.
68. Hu FB, Willett WC, Li T, Stampfer MJ, Colditz GA, Manson JE. Adiposity as compared with physical activity in predicting mortality among women. N Engl J Med 351: 2694-2703, 2004.
69. Hudlicka O, Myrhage R, Cooper J. Growth of capillaries in adult skeletal muscle after chronic stimulation. Bibl Anat 508-509, 1977.
70. Huss J, Torra I, Staels B, Giguere V, Kelly D. Estrogen-related receptor alpha directs peroxisome proliferator-activated receptor alpha signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Mol Cell Biol 24: 9079-9091, 2004.
71. Huss JM, Kopp RP, Kelly DP. Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha. J Biol Chem 277: 40265-40274, 2002.
72. Inbar O, Kaiser P, Tesch P. Relationships between leg muscle fiber type distribution and leg exercise performance. Int J Sports Med 2: 154-159, 1981.
73. Ingjer F. Capillary supply and mitochondrial content of different skeletal muscle fiber types in untrained and endurance-trained men. A histochemical and ultrastructural study. Eur J Appl Physiol Occup Physiol 40: 197-209, 1979.
74. Irrcher I, Adhihetty P, Sheehan T, Joseph A, Hood D. PPARγ coactivator-1α expression during thyroid hormone- and contractile activity- induced mitochondrial adaptations. Am J Physiol Cell Physiol 284: C1669-C1677, 2003.
75. Jäger S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 104: 12017-12022, 2007.
76. Jiang LQ, Garcia-Roves P, de Castro Barbosa T, Zierath JR. Constitutively active calcineurin in skeletal muscle increases endurance performance and mitochondrial respiratory capacity. Am J Physiol Endocrinol Metab 298: E8-E16, 2010.
77. Johannes FJ, Prestle J, Eis S, Oberhagemann P, Pfizenmaier K. PKCu is a novel, atypical member of the protein kinase C family. J Biol Chem 269: 6140-6148, 1994.
78. Jorgensen S, Wojtaszewski J, Viollet B, Andreelli F, Birk J, Hellsten Y, Schjerling P, Vaulont S, Neufer P, Richter E, Pilegaard H. Effects of alpha-AMPK knockout on exercise-induced gene activation in mouse skeletal muscle. FASEB J 19: 1146-1148, 2005.
79. Kang C, O'Moore KM, Dickman JR, Ji LL. Exercise activation of muscle peroxisome proliferator-activated receptor-gamma coactivator- 1alpha signaling is redox sensitive. Free Radic Biol Med 47: 1394-1400, 2009.
80. Kim MS, Fielitz J, McAnally J, Shelton JM, Lemon DD, McKinsey TA, Richardson JA, Bassel-Duby R, Olson EN. Protein kinase D1 stimulates MEF2 activity in skeletal muscle and enhances muscle performance. Mol Cell Biol 28: 3600-3609, 2008.
81. Klitgaard H, Bergman O, Betto R, Salviati G, Schiaffino S, Clausen T, Saltin B. Co-existence of myosin heavy chain I and IIa isoforms in human skeletal muscle fibres with endurance training. Pflügers Arch 416: 470-472, 1990. (Pubitemid 20226165)
82. Kokkinos P, Myers J, Doumas M, Faselis C, Manolis A, Pittaras A, Kokkinos JP, Singh S, Fletcher RD. Exercise capacity and all-cause mortality in prehypertensive men. Am J Hypertens 22: 735-741, 2009.
83. Koves T, Li P, An J, Akimoto T, Slentz D, Ilkayeva O, Dohm G, Yan Z, Newgard C, Muoio D. Peroxisome proliferator-activated receptorgamma co-activator 1alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency. J Biol Chem 280: 33588-33598, 2005.
84. Kraus WE, Torgan CE, Duscha BD, Norris J, Brown SA, Cobb FR, Bales CW, Annex BH, Samsa GP, Houmard JA, Slentz CA. Studies of a targeted risk reduction intervention through defined exercise (STRRIDE). Med Sci Sports Exerc 33: 1774-1784, 2001.
85. Lanza IR, Short DK, Short KR, Raghavakaimal S, Basu R, Joyner MJ, McConnell JP, Nair KS. Endurance exercise as a countermeasure for aging. Diabetes 57: 2933-2942, 2008.
86. Leick L, Hellsten Y, Fentz J, Lyngby SS, Wojtaszewski JFP, Hidalgo J, Pilegaard H. PGC-1α mediates exercise-induced skeletal muscle VEGF expression in mice. Am J Physiol Endocrinol Metab 297: E92-E103, 2009.
87. Leick L, Lyngby SS, Wojtasewski JF, Pilegaard H. PGC-1alpha is required for training-induced prevention of age-associated decline in mitochondrial enzymes in mouse skeletal muscle. Exp Gerontol 45: 336-342, 2010.
88. Leick L, Wojtaszewski JFP, Johansen ST, Kiilerich K, Comes G, Hellsten Y, Hidalgo J, Pilegaard H. PGC-1α is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle. Am J Physiol Endocrinol Metab 294: E463-E474, 2008.
89. Leone T, Lehman J, Finck B, Schaeffer P, Wende A, Boudina S, Courtois M, Wozniak D, Sambandam N, Bernal-Mizrachi C, Chen Z, Holloszy J, Medeiros D, Schmidt R, Saffitz J, Abel E, Semenkovich C, Kelly D. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol 3: e101, 2005.
90. Lillioja S, Young A, Culter C, Ivy J, Abbott W, Zawadzki J, Yki-Jarvinen H, Christin L, Secomb T, Bogardus C. Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man. J Clin Invest 80: 415-424, 1987.
91. Lin J, Wu H, Tarr P, Zhang C, Wu Z, Boss O, Michael L, Puigserver P, Isotani E, Olson E, Lowell B, Bassel-Duby R, Spiegelman B. Transcriptional co-activator PGC-1 alpha drives the formation of slowtwitch muscle fibres. Nature 418: 797-801, 2002.
92. Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jager S, Vianna CR, Reznick RM, Cui L, Manieri M, Donovan MX, Wu Z, Cooper MP, Fan MC, Rohas LM, Zavacki AM, Cinti S, Shulman GI, Lowell BB, Krainc D, Spiegelman BM. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC- 1alpha null mice. Cell 119: 121-135, 2004.
93. Lira VA, Benton CR, Yan Z, Bonen A. PGC-1alpha regulation by exercise training and its influences on muscle function and insulin sensitivity. Am J Physiol Endocrinol Metab 299: E145-E161, 2010.
94. Liu C, Li S, Liu T, Borjigin J, Lin JD. Transcriptional coactivator PGC-1alpha integrates the mammalian clock and energy metabolism. Nature 447: 477-481, 2007.
95. Liu Y, Cseresnyes Z, Randall W, Schneider M. Activity-dependent nuclear translocation and intranuclear distribution of NFATc in adult skeletal muscle fibers. J Cell Biol 155: 27-39, 2001.
96. Lloyd P, Prior B, Yang H, Terjung R. Angiogenic growth factor expression in rat skeletal muscle in response to exercise training. Am J Physiol Heart Circ Physiol 284: H1668-H1678, 2003.
97. Lloyd PG, Prior BM, Li H, Yang HT, Terjung RL. VEGF receptor antagonism blocks arteriogenesis, but only partially inhibits angiogenesis, in skeletal muscle of exercise-trained rats. Am J Physiol Heart Circ Physiol 288: H759-H768, 2005.
98. Long YC, Glund S, Garcia-Roves PM, Zierath JR. Calcineurin regulates skeletal muscle metabolism via coordinated changes in gene expression. J Biol Chem 282: 1607-1614, 2007.
99. Lowell B, Shulman G. Mitochondrial dysfunction and type 2 diabetes. Science 307: 384-387, 2005.
100. Mai J, Edgerton V, Barnard R. Capillarity of red, white and intermediate muscle fibers in trained and untrained guinea pigs. Experientia 26: 1222-1223, 1970.
101. Manson JE, Nathan DM, Krolewski AS, Stampfer MJ, Willett WC, Hennekens CH. A prospective study of exercise and incidence of diabetes among US male physicians. JAMA 268: 63-67, 1992.
102. McArdle A, Pattwell D, Vasilaki A, Griffiths RD, Jackson MJ. Contractile activity-induced oxidative stress: cellular origin and adaptive responses. Am J Physiol Cell Physiol 280: C621-C627, 2001.
103. McCullagh K, Calabria E, Pallafacchina G, Ciciliot S, Serrano A, Argentini C, Kalhovde J, Lomo T, Schiaffino S. NFAT is a nerve activity sensor in skeletal muscle and controls activity-dependent myosin switching. Proc Natl Acad Sci USA 101: 10590-10595, 2004.
104. McGee S, Hargreaves M. Exercise and myocyte enhancer factor 2 regulation in human skeletal muscle. Diabetes 53: 1208-1214, 2004. (Pubitemid 38569005)
105. McKinsey T, Zhang C, Lu J, Olson E. Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature 408: 106-111, 2000.
106. McKinsey T, Zhang C, Olson E. Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5. Proc Natl Acad Sci USA 97: 14400-14405, 2000.
107. Michael L, Wu Z, Cheatham R, Puigserver P, Adelmant G, Lehman J, Kelly D, Spiegelman B. Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1. Proc Natl Acad Sci USA 98: 3820-3825, 2001.
108. Miyazaki M, Hitomi Y, Kizaki T, Ohno H, Haga S, Takemasa T. Contribution of the calcineurin signaling pathway to overload-induced skeletal muscle fiber-type transition. J Physiol Pharmacol 55: 751-764, 2004.
109. Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM. Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc Natl Acad Sci USA 101: 6570-6575, 2004.
110. Mukwevho E, Kohn TA, Lang D, Nyatia E, Smith J, Ojuka EO. Caffeine induces hyperacetylation of histones at the MEF2 site on the Glut4 promoter and increases MEF2A binding to the site via a CaMKdependent mechanism. Am J Physiol Endocrinol Metab 294: E582-E588, 2008.
111. Myrhage R, Hudlicka O. Capillary growth in chronically stimulated adult skeletal muscle as studied by intravital microscopy and histological methods in rabbits and rats. Microvasc Res 16: 73-90, 1978.
112. Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM. AMPK and PPARdelta agonists are exercise mimetics. Cell 134: 405-415, 2008.
113. Naya F, Mercer B, Shelton J, Richardson J, Williams R, Olson E. Stimulation of slow skeletal muscle fiber gene expression by calcineurin in vivo. J Biol Chem 275: 4545-4548, 2000.
114. Oh M, Rybkin II, Copeland V, Czubryt M, Shelton J, van Rooij E, Richardson J, Hill J, De Windt L, Bassel-Duby R, Olson E, Rothermel B. Calcineurin is necessary for the maintenance but not embryonic development of slow muscle fibers. Mol Cell Biol 25: 6629-6638, 2005.
115. Olfert IM, Howlett RA, Tang K, Dalton ND, Gu Y, Peterson KL, Wagner PD, Breen EC. Muscle-specific VEGF deficiency greatly reduces exercise endurance in mice. J Physiol 587: 1755-1767, 2009.
116. Olfert IM, Howlett RA, Wagner PD, Breen EC. Myocyte vascular endothelial growth factor is required for exercise-induced skeletal muscle angiogenesis. Am J Physiol Regul Integr Comp Physiol 299: R1059-R1067, 2010.
117. Olson E, Williams R. Calcineurin signaling and muscle remodeling. Cell 101: 689-692, 2000.
118. Parsons S, Wilkins B, Bueno O, Molkentin J. Altered skeletal muscle phenotypes in calcineurin Aalpha and Abeta gene-targeted mice. Mol Cell Biol 23: 4331-4343, 2003.
119. Parsons SA, Millay DP, Wilkins BJ, Bueno OF, Tsika GL, Neilson JR, Liberatore CM, Yutzey KE, Crabtree GR, Tsika RW, Molkentin JD. Genetic loss of calcineurin blocks mechanical overload-induced skeletal muscle fiber type switching but not hypertrophy. J Biol Chem 279: 26192-26200, 2004.
120. Pattwell DM, McArdle A, Morgan JE, Patridge TA, Jackson MJ. Release of reactive oxygen and nitrogen species from contracting skeletal muscle cells. Free Radic Biol Med 37: 1064-1072, 2004.
121. Perseghin G, Price T, Petersen K, Roden M, Cline G, Gerow K, Rothman D, Shulman G. Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects. N Engl J Med 335: 1357-1362, 1996.
122. Pilegaard H, Saltin B, Neufer P. Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. J Physiol 546: 851-858, 2003.
123. Pogozelski AR, Geng T, Li P, Yin X, Lira VA, Zhang M, Chi JT, Yan Z. p38gamma mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice. PLoS ONE 4: e7934, 2009.
124. Potthoff M, Wu H, Arnold M, Shelton J, Backs J, McAnally J, Richardson J, Bassel-Duby R, Olson E. Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J Clin Invest 117: 2459-2467, 2007.
125. Prince FP, Hikida RS, Hagerman FC, Staron RS, Allen WH. A morphometric analysis of human muscle fibers with relation to fiber types and adaptations to exercise. J Neurol Sci 49: 165-179, 1981.
126. Prior B, Yang H, Terjung R. What makes vessels grow with exercise training? J Appl Physiol 97: 1119-1128, 2004.
127. Puigserver P, Rhee J, Lin J, Wu Z, Yoon J, Zhang C, Krauss S, Mootha V, Lowell B, Spiegelman B. Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator- 1. Mol Cell 8: 971-982, 2001.
128. Puigserver P, Spiegelman B. Peroxisome proliferator-activated receptor- gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24: 78-90, 2003
129. Puigserver P, Wu Z, Park C, Graves R, Wright M, Spiegelman B. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92: 829-839, 1998.
130. Raney MA, Turcotte LP. Evidence for the involvement of CaMKII and AMPK in Ca2+-dependent signaling pathways regulating FA uptake and oxidation in contracting rodent muscle. J Appl Physiol 104: 1366-1373, 2008.
131. Reichmann H, Hoppeler H, Mathieu-Costello O, von Bergen F, Pette D. Biochemical and ultrastructural changes of skeletal muscle mitochondria after chronic electrical stimulation in rabbits. Pflügers Arch 404: 1-9, 1985.
132. Reid MB, Haack KE, Franchek KM, Valberg PA, Kobzik L, West MS. Reactive oxygen in skeletal muscle. I. Intracellular oxidant kinetics and fatigue in vitro. J Appl Physiol 73: 1797-1804, 1992.
133. Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Blüher M. Antioxidants prevent healthpromoting effects of physical exercise in humans. Proc Natl Acad Sci USA 106: 8665-8670, 2009.
134. Rivero JL, Talmadge RJ, Edgerton VR. Fibre size and metabolic properties of myosin heavy chain-based fibre types in rat skeletal muscle. J Muscle Res Cell Motil 19: 733-742, 1998.
135. Rivero JL, Talmadge RJ, Edgerton VR. Interrelationships of myofibrillar ATPase activity and metabolic properties of myosin heavy chainbased fibre types in rat skeletal muscle. Histochem Cell Biol 111: 277-287, 1999.
136. Rockl KS, Witczak CA, Goodyear LJ. Signaling mechanisms in skeletal muscle: acute responses and chronic adaptations to exercise. IUBMB Life 60: 145-153, 2008.
137. Röckl KSC, Hirshman MF, Brandauer J, Fujii N, Witters LA, Goodyear LJ. Skeletal muscle adaptation to exercise training: AMPactivated protein kinase mediates muscle fiber type shift. Diabetes 56: 2062-2069, 2007.
138. Romanello V, Guadagnin E, Gomes L, Roder I, Sandri C, Petersen Y, Milan G, Masiero E, Del Piccolo P, Foretz M, Scorrano L, Rudolf R, Sandri M. Mitochondrial fission and remodelling contributes to muscle atrophy. EMBO J 29: 1774-1785, 2010.
139. Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y. Heart disease and stroke statistics-2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 115: e69-e171, 2007.
140. 2+-calmodulin- dependent protein kinase II activity in human skeletal muscle. J Physiol 553: 303-309, 2003.
141. 2+-calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise. J Physiol 574: 889-903, 2006.
142. Russell A, Feilchenfeldt J, Schreiber S, Praz M, Crettenand A, Gobelet C, Meier C, Bell D, Kralli A, Giacobino J, Deriaz O. Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptor-gamma coactivator- 1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle. Diabetes 52: 2874-2881, 2003.
143. Ryder J, Bassel-Duby R, Olson E, Zierath J. Skeletal muscle reprogramming by activation of calcineurin improves insulin action on metabolic pathways. J Biol Chem 278: 44298-44304, 2003.
144. Safdar A, Abadi A, Akhtar M, Hettinga BP, Tarnopolsky MA. miRNA in the regulation of skeletal muscle adaptation to acute endurance exercise in C57Bl/6J male mice. PLoS ONE 4: e5610, 2009.
145. Salmons S, Henriksson J. The adaptive response of skeletal muscle to increased use. Muscle Nerve 4: 94-105, 1981.
146. Saltin B, Nazar K, Costill DL, Stein E, Jansson E, Essen B, Gollnick D. The nature of the training response; peripheral and central adaptations of one-legged exercise. Acta Physiol Scand 96: 289-305, 1976.
147. Saltin B, Rowell LB. Functional adaptations to physical activity and inactivity. Fed Proc 39: 1506-1513, 1980.
148. Scarpulla RC. Nuclear control of respiratory chain expression by nuclear respiratory factors and PGC-1-related coactivator. Ann NY Acad Sci 1147: 321-334, 2008.
149. Scarpulla RC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 88: 611-638, 2008.
150. Schantz PG, Dhoot GK. Coexistence of slow and fast isoforms of contractile and regulatory proteins in human skeletal muscle fibres induced by endurance training. Acta Physiol Scand 131: 147-154, 1987.
151. Schiaffino S, Sandri M, Murgia M. Activity-dependent signaling pathways controlling muscle diversity and plasticity. Physiology 22: 269-278, 2007.
152. Schrauwen-Hinderling VB, Kooi ME, Hesselink MK, Jeneson JA, Backes WH, van Echteld CJ, van Engelshoven JM, Mensink M, Schrauwen P. Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects. Diabetologia 50: 113-120, 2007.
153. Schuler M, Ali F, Chambon C, Duteil D, Bornert JM, Tardivel A, Desvergne B, Wahli W, Chambon P, Metzger D. PGC1alpha expression is controlled in skeletal muscles by PPARbeta, whose ablation results in fiber-type switching, obesity, and type 2 diabetes. Cell Metab 4: 407-414, 2006.
154. Serrano A, Murgia M, Pallafacchina G, Calabria E, Coniglio P, Lomo T, Schiaffino S. Calcineurin controls nerve activity-dependent specification of slow skeletal muscle fibers but not muscle growth. Proc Natl Acad Sci USA 98: 13108-13113, 2001.
155. Seth A, Steel JH, Nichol D, Pocock V, Kumaran MK, Fritah A, Mobberley M, Ryder TA, Rowlerson A, Scott J, Poutanen M, White R, Parker M. The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle. Cell Metab 6: 236-245, 2007.
156. Shen T, Liu Y, Cseresnyés Z, Hawkins A, Randall WR, Schneider MF. Activity- and calcineurin-independent nuclear shuttling of NFATc1, but not NFATc3, in adult skeletal muscle fibers. Mol Biol Cell 17: 1570-1582, 2006.
157. Shen T, Liu Y, Randall WR, Schneider MF. Parallel mechanisms for resting nucleo-cytoplasmic shuttling and activity dependent translocation provide dual control of transcriptional regulators HDAC and NFAT in skeletal muscle fiber type plasticity. J Muscle Res Cell Motil 27: 405-411, 2006.
158. Short K, Vittone J, Bigelow M, Proctor D, Rizza R, Coenen-Schimke J, Nair K. Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity. Diabetes 52: 1888- 1896, 2003.
159. Silveira LR, Pilegaard H, Kusuhara K, Curi R, Hellsten Y. The contraction induced increase in gene expression of peroxisome proliferator- activated receptor (PPAR)-gamma coactivator 1alpha (PGC-1alpha), mitochondrial uncoupling protein 3 (UCP3) and hexokinase II (HKII) in primary rat skeletal muscle cells is dependent on reactive oxygen species. Biochim Biophys Acta 1763: 969-976, 2006.
160. Sjogaard G, Saltin B. Extra- and intracellular water spaces in muscles of man at rest and with dynamic exercise. Am J Physiol Regul Integr Comp Physiol 243: R271-R280, 1982.
161. Smerdu V, Karsch-Mizrachi I, Campione M, Leinwand L, Schiaffino S. Type IIx myosin heavy chain transcripts are expressed in type IIb fibers of human skeletal muscle. Am J Physiol Cell Physiol 267: C1723-C1728, 1994.
162. Smith JA, Kohn TA, Chetty AK, Ojuka EO. CaMK activation during exercise is required for histone hyperacetylation and MEF2A binding at the MEF2 site on the Glut4 gene. Am J Physiol Endocrinol Metab 295: E698-E704, 2008.
163. Stamler R, Stamler J, Gosch FC, McDonald AM. Primary prevention of hypertension-a randomized controlled trial. Ann Clin Res 16, Suppl 43: 136-142, 1984.
164. Streja D, Mymin D. Moderate exercise and high-density lipoproteincholesterol. Observations during a cardiac rehabilitation program. JAMA 242: 2190-2192, 1979.
165. Svedenhag J, Henriksson J, Juhlin-Dannfelt A. β-Adrenergic blockade and training in human subjects: effects on muscle metabolic capacity. Am J Physiol Endocrinol Metab 247: E305-E311, 1984.
166. Terada S, Goto M, Kato M, Kawanaka K, Shimokawa T, Tabata I. Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle. Biochem Biophys Res Commun 296: 350-354, 2002.
167. Termin A, Staron RS, Pette D. Myosin heavy chain isoforms in histochemically defined fiber types of rat muscle. Histochemistry 92: 453-457, 1989.
168. Thyfault JP, Cree MG, Zheng D, Zwetsloot JJ, Tapscott EB, Koves TR, Ilkayeva O, Wolfe RR, Muoio DM, Dohm GL. Contraction of insulin-resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism. Am J Physiol Cell Physiol 292: C729-C739, 2007.
169. Timmons JA, Norrbom J, Scheele C, Thonberg H, Wahlestedt C, Tesch P. Expression profiling following local muscle inactivity in humans provides new perspective on diabetes-related genes. Genomics 87: 165-172, 2006.
170. Torgan CE, Daniels MP. Regulation of myosin heavy chain expression during rat skeletal muscle development in vitro. Mol Biol Cell 12: 1499-1508, 2001.
171. Tsika RW, Herrick RE, Baldwin KM. Subunit composition of rodent isomyosins and their distribution in hindlimb skeletal muscles. J Appl Physiol 63: 2101-2110, 1987.
172. 2+ uptake and impairs contractile function. J Biol Chem 277: 44740-44746, 2002.
173. Valverde AM, Sinnett-Smith J, Van Lint J, Rozengurt E. Molecular cloning and characterization of protein kinase D: a target for diacylglycerol and phorbol esters with a distinctive catalytic domain. Proc Natl Acad Sci USA 91: 8572-8576, 1994.
174. Van Lint JV, Sinnett-Smith J, Rozengurt E. Expression and characterization of PKD, a phorbol ester and diacylglycerol-stimulated serine protein kinase. J Biol Chem 270: 1455-1461, 1995.
175. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39: 359-407, 2005.
176. Wallberg-Henriksson H, Gunnarsson R, Henriksson J, DeFronzo R, Felig P, Ostman J, Wahren J. Increased peripheral insulin sensitivity and muscle mitochondrial enzymes but unchanged blood glucose control in type I diabetics after physical training. Diabetes 31: 1044-1050, 1982.
177. Wang Y, Zhang C, Yu R, Cho H, Nelson M, Bayuga-Ocampo C, Ham J, Kang H, Evans R. Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biol 2: e294, 2004.
178. Waters R, Rotevatn S, Li P, Annex B, Yan Z. Voluntary running induces fiber type-specific angiogenesis in mouse skeletal muscle. Am J Physiol Cell Physiol 287: C1342-C1348, 2004.
179. Wende AR, Schaeffer PJ, Parker GJ, Zechner C, Han DH, Chen MM, Hancock CR, Lehman JJ, Huss JM, McClain DA, Holloszy JO, Kelly DP. A role for the transcriptional coactivator PGC-1alpha in muscle refueling. J Biol Chem 282: 36642-36651, 2007.
180. Widegren U, Jiang X, Krook A, Chibalin A, Bjornholm M, Tally M, Roth R, Henriksson J, Wallberg-Henriksson H, Zierath J. Divergent effects of exercise on metabolic and mitogenic signaling pathways in human skeletal muscle. FASEB J 12: 1379-1389, 1998.
181. Williams RS, Neufer PD. Regulation of gene expression in skeletal muscle by contractile activity. In: Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, MD: Am. Physiol. Soc., 1996, sect. 12, chapt. 25, p. 1124-1150.
182. Wilwert JL, Madhoun NM, Coughlin DJ. Parvalbumin correlates with relaxation rate in the swimming muscle of sheepshead and kingfish. J Exp Biol 209: 227-237, 2006.
183. Winder W, Hardie D. 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.
184. Winder WW, Holmes BF, Rubink DS, Jensen EB, Chen M, Holloszy JO. Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle. J Appl Physiol 88: 2219-2226, 2000.
185. Witzmann FA, Kim DH, Fitts RH. Hindlimb immobilization: lengthtension and contractile properties of skeletal muscle. J Appl Physiol 53: 335-345, 1982.
186. Wojtaszewski J, Nielsen P, Hansen B, Richter E, Kiens B. Isoformspecific and exercise intensity-dependent activation of 5′-AMP-activated protein kinase in human skeletal muscle. J Physiol 528: 221-226, 2000.
187. Wright D, Geiger P, Han D, Jones T, Holloszy J. Calcium induces increases in peroxisome proliferator-activated receptor gamma coactivator- 1alpha and mitochondrial biogenesis by a pathway leading to p38 mitogen-activated protein kinase activation. J Biol Chem 282: 18793-18799, 2007.
188. Wright D, Han D, Garcia-Roves P, Geiger P, Jones T, Holloszy J. Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression. J Biol Chem 282: 194-199, 2007.
189. Wu H, Kanatous S, Thurmond F, Gallardo T, Isotani E, Bassel-Duby R, Williams R. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 296: 349-352, 2002.
190. Wu H, Naya F, McKinsey T, Mercer B, Shelton J, Chin E, Simard A, Michel R, Bassel-Duby R, Olson E, Williams R. MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type. EMBO J 19: 1963-1973, 2000.
191. Wu H, Rothermel B, Kanatous S, Rosenberg P, Naya F, Shelton J, Hutcheson K, DiMaio J, Olson E, Bassel-Duby R, Williams R. Activation of MEF2 by muscle activity is mediated through a calcineurin- dependent pathway. EMBO J 20: 6414-6423, 2001.
192. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla R, Spiegelman B. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98: 115-124, 1999.
193. Yfanti C, Akerstrom T, Nielsen S, Nielsen AR, Mounier R, Mortensen OH, Lykkesfeldt J, Rose AJ, Fischer CP, Pedersen BK. Antioxidant supplementation does not alter endurance training adaptation. Med Sci Sports Exerc 42: 1388-1395, 2010.
194. Zechner C, Lai L, Fong J, Geng T, Yan Z, Rumsey J, Collia D, Chen Z, Wozniak D, Leone T, Kelly D. Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivity. Cell Metab. In press.
195. Zhao M, New L, Kravchenko VV, Kato Y, Gram H, di Padova F, Olson EN, Ulevitch RJ, Han J. Regulation of the MEF2 family of transcription factors by p38. Mol Cell Biol 19: 21-30, 1999.
196. Zong H, Ren J, Young L, Pypaert M, Mu J, Birnbaum M, Shulman G. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci USA 99: 15983-15987, 2002.
197. Zugaza JL, Sinnett-Smith J, Van Lint J, Rozengurt E. Protein kinase D (PKD) activation in intact cells through a protein kinase C-dependent signal transduction pathway. EMBO J 15: 6220-6230, 1996.
198. Zwetsloot KA, Westerkamp LM, Holmes BF, Gavin TP. AMPK regulates basal skeletal muscle capillarization and VEGF expression, but is not necessary for the angiogenic response to exercise. J Physiol 586: 6021-6035, 2008.