AMPK and exercise: Glucose uptake and insulin sensitivity

Diabetes and Metabolism Journal

Volumn 37, Issue 1, 2013, Pages 1-21

  O'Neill, Hayley M ^a  

^a ST VINCENT'S INSTITUTE OF MEDICAL RESEARCH   (Australia)

Author keywords

AMPK; Exercise; Glucose uptake; Insulin resistance; Obesity

Indexed keywords

ADIPONECTIN; GLUCOSE 6 PHOSPHATE; GLUCOSE TRANSPORTER 4; GLYCOGEN SYNTHASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE ALPHA2; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE BETA; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE GAMMA; INTERLEUKIN 6; MAMMALIAN TARGET OF RAPAMYCIN; MEMBRANE PROTEIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE; PROTEIN TBC1D1; PROTEIN TBC1D4; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; BIOGENESIS; CARBOXY TERMINAL SEQUENCE; ENZYME ACTIVITY; EXERCISE; FATTY ACID OXIDATION; FATTY ACID TRANSPORT; GLUCONEOGENESIS; GLUCOSE TRANSPORT; GLUCOSE UTILIZATION; GLYCOGEN SYNTHESIS; HUMAN; INSULIN RESISTANCE; INSULIN SENSITIVITY; INSULIN TOLERANCE TEST; LIPID METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OXYGEN CONSUMPTION; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN DEPHOSPHORYLATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; UBIQUITINATION; WOLFF PARKINSON WHITE SYNDROME;

EID: 84874993428     PISSN: 22336079     EISSN: 22336087     Source Type: Journal    
DOI: 10.4093/dmj.2013.37.1.1     Document Type: Review

References (176)

1. Dyck JR, Gao G, Widmer J, Stapleton D, Fernandez CS, Kemp BE, Witters LA. Regulation of 5'-AMP-activated protein kinase activity by the noncatalytic beta and gamma subunits. J Biol Chem 1996;271:17798-803.
2. Cheung PC, Salt IP, Davies SP, Hardie DG, Carling D. Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding. Biochem J 2000;346 Pt 3:659-69.
3. Luptak I, Shen M, He H, Hirshman MF, Musi N, Goodyear LJ, Yan J, Wakimoto H, Morita H, Arad M, Seidman CE, Seidman JG, Ingwall JS, Balschi JA, Tian R. Aberrant activation of AMPactivated protein kinase remodels metabolic network in favor of cardiac glycogen storage. J Clin Invest 2007;117:1432-9.
4. Barnes BR, Marklund S, Steiler TL, Walter M, Hjalm G, Amarger V, Mahlapuu M, Leng Y, Johansson C, Galuska D, Lindgren K, Abrink M, Stapleton D, Zierath JR, Andersson L. The 5'-AMP-activated protein kinase gamma3 isoform has a key role in carbohydrate and lipid metabolism in glycolytic skeletal muscle. J Biol Chem 2004;279:38441-7.
5. Mahlapuu M, Johansson C, Lindgren K, Hjalm G, Barnes BR, Krook A, Zierath JR, Andersson L, Marklund S. Expression profiling of the gamma-subunit isoforms of AMP-activated protein kinase suggests a major role for gamma3 in white skeletal muscle. Am J Physiol Endocrinol Metab 2004;286:E194-200.
6. Yu H, Fujii N, Hirshman MF, Pomerleau JM, Goodyear LJ. Cloning and characterization of mouse 5'-AMP-activated protein kinase gamma3 subunit. Am J Physiol Cell Physiol 2004; 286:C283-92.
7. Chen Z, Heierhorst J, Mann RJ, Mitchelhill KI, Michell BJ, Witters LA, Lynch GS, Kemp BE, Stapleton D. Expression of the AMP-activated protein kinase beta1 and beta2 subunits in skeletal muscle. FEBS Lett 1999;460:343-8.
8. Murphy RM. Enhanced technique to measure proteins in single segments of human skeletal muscle fibers: fiber-type dependence of AMPK-alpha1 and -beta1. J Appl Physiol 2011; 110:820-5.
9. Mortensen B, Poulsen P, Wegner L, Stender-Petersen KL, Ribel-Madsen R, Friedrichsen M, Birk JB, Vaag A, Wojtaszewski JF. Genetic and metabolic effects on skeletal muscle AMPK in young and older twins. Am J Physiol Endocrinol Metab 2009; 297:E956-64.
10. Wojtaszewski JF, Birk JB, Frosig C, Holten M, Pilegaard H, Dela F. 5'AMP activated protein kinase expression in human skeletal muscle: effects of strength training and type 2 diabetes. J Physiol 2005;564(Pt 2):563-73.
11. Sanders MJ, Grondin PO, Hegarty BD, Snowden MA, Carling D. Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. Biochem J 2007;403: 139-48.
12. Oakhill JS, Steel R, Chen ZP, Scott JW, Ling N, Tam S, Kemp BE. AMPK is a direct adenylate charge-regulated protein kinase. Science 2011;332:1433-5.
13. Xiao B, Sanders MJ, Underwood E, Heath R, Mayer FV, Carmena D, Jing C, Walker PA, Eccleston JF, Haire LF, Saiu P, Howell SA, Aasland R, Martin SR, Carling D, Gamblin SJ. Structure of mammalian AMPK and its regulation by ADP. Nature 2011;472:230-3.
14. Hawley SA, Davison M, Woods A, Davies SP, Beri RK, Carling D, 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 AMPactivated protein kinase. J Biol Chem 1996;271:27879-87.
15. Hawley SA, Boudeau J, Reid JL, Mustard KJ, Udd L, Makela TP, Alessi DR, Hardie DG. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol 2003;2:28.
16. Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LG, Neumann D, Schlattner U, Wallimann T, Carlson M, Carling D. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 2003;13:2004-8.
17. Koh HJ, Arnolds DE, Fujii N, Tran TT, Rogers MJ, Jessen N, Li Y, Liew CW, Ho RC, Hirshman MF, Kulkarni RN, Kahn CR, Goodyear LJ. Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3. Mol Cell Biol 2006;26:8217-27.
18. Sakamoto K, McCarthy A, Smith D, Green KA, Grahame Hardie D, Ashworth A, Alessi DR. Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction. EMBO J 2005;24:1810-20.
19. Thomson DM, Porter BB, Tall JH, Kim HJ, Barrow JR, Winder WW. Skeletal muscle and heart LKB1 deficiency causes decreased voluntary running and reduced muscle mitochondrial marker enzyme expression in mice. Am J Physiol Endocrinol Metab 2007;292:E196-202.
20. Hurley RL, Anderson KA, Franzone JM, Kemp BE, Means AR, Witters LA. The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J Biol Chem 2005;280:29060-6.
21. Hawley SA, Pan DA, Mustard KJ, Ross L, Bain J, Edelman AM, Frenguelli BG, Hardie DG. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab 2005;2:9-19.
22. Woods A, Dickerson K, Heath R, Hong SP, Momcilovic M, Johnstone SR, Carlson M, Carling D. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMPactivated protein kinase in mammalian cells. Cell Metab 2005;2:21-33.
23. DeFronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 2009; 32 Suppl 2:S157-63.
24. DeFronzo RA, Ferrannini E, Sato Y, Felig P, Wahren J. Synergistic interaction between exercise and insulin on peripheral glucose uptake. J Clin Invest 1981;68:1468-74.
25. Thiebaud D, Jacot E, DeFronzo RA, Maeder E, Jequier E, Felber JP. The effect of graded doses of insulin on total glucose uptake, glucose oxidation, and glucose storage in man. Diabetes 1982;31:957-63.
26. Jorgensen SB, Viollet B, Andreelli F, Frosig C, Birk JB, Schjerling P, Vaulont S, Richter EA, Wojtaszewski JF. Knockout of the alpha2 but not alpha1 5'-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle. J Biol Chem 2004;279:1070-9.
27. Dzamko N, van Denderen BJ, Hevener AL, Jorgensen SB, Honeyman J, Galic S, Chen ZP, Watt MJ, Campbell DJ, Steinberg GR, Kemp BE. AMPK beta1 deletion reduces appetite, preventing obesity and hepatic insulin resistance. J Biol Chem 2010;285:115-22.
28. Steinberg GR, O'Neill HM, Dzamko NL, Galic S, Naim T, Koopman R, Jorgensen SB, Honeyman J, Hewitt K, Chen ZP, Schertzer JD, Scott JW, Koentgen F, Lynch GS, Watt MJ, van Denderen BJ, Campbell DJ, Kemp BE. Whole body deletion of AMP-activated protein kinase {beta}2 reduces muscle AMPK activity and exercise capacity. J Biol Chem 2010;285: 37198-209.
29. Dasgupta B, Ju JS, Sasaki Y, Liu X, Jung SR, Higashida K, Lindquist D, Milbrandt J. The AMPK beta2 subunit is required for energy homeostasis during metabolic stress. Mol Cell Biol 2012;32:2837-48.
30. O'Neill HM, Maarbjerg SJ, Crane JD, Jeppesen J, Jorgensen SB, Schertzer JD, Shyroka O, Kiens B, van Denderen BJ, Tarnopolsky MA, Kemp BE, Richter EA, Steinberg GR. AMP-activated protein kinase (AMPK) beta1beta2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. Proc Natl Acad Sci U S A 2011;108:16092-7.
31. Mu J, Brozinick JT Jr, Valladares O, Bucan M, Birnbaum MJ. A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle. Mol Cell 2001;7:1085-94.
32. Fujii N, Hirshman MF, Kane EM, Ho RC, Peter LE, Seifert MM, Goodyear LJ. AMP-activated protein kinase alpha2 activity is not essential for contraction- and hyperosmolarityinduced glucose transport in skeletal muscle. J Biol Chem 2005;280:39033-41.
33. Viollet B, Andreelli F, Jorgensen SB, Perrin C, Geloen A, Flamez D, Mu J, Lenzner C, Baud O, Bennoun M, Gomas E, Nicolas G, Wojtaszewski JF, Kahn A, Carling D, Schuit FC, Birnbaum MJ, Richter EA, Burcelin R, Vaulont S. The AMPactivated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity. J Clin Invest 2003;111:91-8.
34. Dzamko N, Schertzer JD, Ryall JG, Steel R, Macaulay SL, Wee S, Chen ZP, Michell BJ, Oakhill JS, Watt MJ, Jorgensen SB, Lynch GS, Kemp BE, Steinberg GR. AMPK-independent pathways regulate skeletal muscle fatty acid oxidation. J Physiol 2008;586:5819-31.
35. Viollet B, Andreelli F, Jorgensen SB, Perrin C, Flamez D, Mu J, Wojtaszewski JF, Schuit FC, Birnbaum M, Richter E, Burcelin R, Vaulont S. Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models. Biochem Soc Trans 2003;31:216-9.
36. Beck Jorgensen S, O'Neill HM, Hewitt K, Kemp BE, Steinberg GR. Reduced AMP-activated protein kinase activity in mouse skeletal muscle does not exacerbate the development of insulin resistance with obesity. Diabetologia 2009;52:2395-404.
37. Fujii N, Ho RC, Manabe Y, Jessen N, Toyoda T, Holland WL, Summers SA, Hirshman MF, Goodyear LJ. Ablation of AMPactivated protein kinase alpha2 activity exacerbates insulin resistance induced by high-fat feeding of mice. Diabetes 2008; 57:2958-66.
38. Quinn JM, Tam S, Sims NA, Saleh H, McGregor NE, Poulton IJ, Scott JW, Gillespie MT, Kemp BE, van Denderen BJ. Germline deletion of AMP-activated protein kinase beta subunits reduces bone mass without altering osteoclast differentiation or function. FASEB J 2010;24:275-85.
39. Egan D, Kim J, Shaw RJ, Guan KL. The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR. Autophagy 2011;7:643-4.
40. Nilsson EC, Long YC, Martinsson S, Glund S, Garcia-Roves P, Svensson LT, Andersson L, Zierath JR, Mahlapuu M. Opposite transcriptional regulation in skeletal muscle of AMPactivated protein kinase gamma3 R225Q transgenic versus knock-out mice. J Biol Chem 2006;281:7244-52.
41. 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 2010;11:213-9.
42. Costford SR, Kavaslar N, Ahituv N, Chaudhry SN, Schackwitz WS, Dent R, Pennacchio LA, McPherson R, Harper ME. Gain-of-function R225W mutation in human AMPKgamma(3) causing increased glycogen and decreased triglyceride in skeletal muscle. PLoS One 2007;2:e903.
43. Crawford SA, Costford SR, Aguer C, Thomas SC, deKemp RA, DaSilva JN, Lafontaine D, Kendall M, Dent R, Beanlands RS, McPherson R, Harper ME. Naturally occurring R225W mutation of the gene encoding AMP-activated protein kinase (AMPK)gamma(3) results in increased oxidative capacity and glucose uptake in human primary myotubes. Diabetologia 2010;53:1986-97.
44. Arad M, Benson DW, Perez-Atayde AR, McKenna WJ, Sparks EA, Kanter RJ, McGarry K, Seidman JG, Seidman CE. Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest 2002;109:357-62.
45. Milan D, Jeon JT, Looft C, Amarger V, Robic A, Thelander M, Rogel-Gaillard C, Paul S, Iannuccelli N, Rask L, Ronne H, Lundstrom K, Reinsch N, Gellin J, Kalm E, Roy PL, Chardon P, Andersson L. A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle. Science 2000; 288:1248-51.
46. Gollob MH, Seger JJ, Gollob TN, Tapscott T, Gonzales O, Bachinski L, Roberts R. Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation 2001;104:3030-3.
47. Gollob MH, Green MS, Tang AS, Gollob T, Karibe A, Ali Hassan AS, Ahmad F, Lozado R, Shah G, Fananapazir L, Bachinski LL, Roberts R. Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. N Engl J Med 2001;344:1823-31.
48. Barnes BR, Glund S, Long YC, Hjalm G, Andersson L, Zierath JR. 5'-AMP-activated protein kinase regulates skeletal muscle glycogen content and ergogenics. FASEB J 2005;19: 773-9.
49. Frosig C, Jorgensen SB, Hardie DG, Richter EA, Wojtaszewski JF. 5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle. Am J Physiol Endocrinol Metab 2004;286: E411-7.
50. Sahlin K, Tonkonogi M, Soderlund K. Energy supply and muscle fatigue in humans. Acta Physiol Scand 1998;162:261-6.
51. Hayashi T, Hirshman MF, Kurth EJ, Winder WW, Goodyear LJ. Evidence for 5' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes 1998;47:1369-73.
52. Hutber CA, Hardie DG, Winder WW. Electrical stimulation inactivates muscle acetyl-CoA carboxylase and increases AMP-activated protein kinase. Am J Physiol 1997;272(2 Pt 1):E262-6.
53. Ihlemann J, Ploug T, Hellsten Y, Galbo H. Effect of tension on contraction-induced glucose transport in rat skeletal muscle. Am J Physiol 1999;277(2 Pt 1):E208-14.
54. Rasmussen BB, Hancock CR, Winder WW. Postexercise recovery of skeletal muscle malonyl-CoA, acetyl-CoA carboxylase, and AMP-activated protein kinase. J Appl Physiol 1998; 85:1629-34.
55. Rasmussen BB, Winder WW. Effect of exercise intensity on skeletal muscle malonyl-CoA and acetyl-CoA carboxylase. J Appl Physiol 1997;83:1104-9.
56. Vavvas D, Apazidis A, Saha AK, Gamble J, Patel A, Kemp BE, Witters LA, Ruderman NB. Contraction-induced changes in acetyl-CoA carboxylase and 5'-AMP-activated kinase in skeletal muscle. J Biol Chem 1997;272:13255-61.
57. Wojtaszewski JF, Nielsen P, Hansen BF, Richter EA, Kiens B. Isoform-specific and exercise intensity-dependent activation of 5'-AMP-activated protein kinase in human skeletal muscle. J Physiol 2000;528 Pt 1:221-6.
58. Chen ZP, Stephens TJ, Murthy S, Canny BJ, Hargreaves M, Witters LA, Kemp BE, McConell GK. Effect of exercise intensity on skeletal muscle AMPK signaling in humans. Diabetes 2003;52:2205-12.
59. Fujii N, Hayashi T, Hirshman MF, Smith JT, Habinowski SA, Kaijser L, Mu J, Ljungqvist O, Birnbaum MJ, Witters LA, Thorell A, Goodyear LJ. Exercise induces isoform-specific increase in 5'AMP-activated protein kinase activity in human skeletal muscle. Biochem Biophys Res Commun 2000;273: 1150-5.
60. Winder WW, Hardie DG. Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am J Physiol 1996;270(2 Pt 1):E299-304.
61. Winder WW, Wilson HA, Hardie DG, Rasmussen BB, Hutber CA, Call GB, Clayton RD, Conley LM, Yoon S, Zhou B. Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A. J Appl Physiol 1997;82:219-25.
62. Chen TC, Hsieh SS. The effects of repeated maximal voluntary isokinetic eccentric exercise on recovery from muscle damage. Res Q Exerc Sport 2000;71:260-6.
63. Hayashi T, Hirshman MF, Fujii N, Habinowski SA, Witters LA, Goodyear LJ. Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism. Diabetes 2000;49:527-31.
64. Kennedy JW, Hirshman MF, Gervino EV, Ocel JV, Forse RA, Hoenig SJ, Aronson D, Goodyear LJ, Horton ES. Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes. Diabetes 1999;48:1192-7.
65. Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P, Hemmings BA. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 1996;15:6541-51.
66. Alessi DR, James SR, Downes CP, Holmes AB, Gaffney PR, Reese CB, Cohen P. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Curr Biol 1997;7:261-9.
67. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005;307:1098-101.
68. Kramer HF, Witczak CA, Taylor EB, Fujii N, Hirshman MF, Goodyear LJ. AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle. J Biol Chem 2006;281:31478-85.
69. Sano H, Kane S, Sano E, Miinea CP, Asara JM, Lane WS, Garner CW, Lienhard GE. Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation. J Biol Chem 2003;278:14599-602.
70. Chen S, Murphy J, Toth R, Campbell DG, Morrice NA, Mackintosh C. Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators. Biochem J 2008;409:449-59.
71. Ishikura S, Klip A. Muscle cells engage Rab8A and myosin Vb in insulin-dependent GLUT4 translocation. Am J Physiol Cell Physiol 2008;295:C1016-25.
72. Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001;414:799-806.
73. Cartee GD, Funai K. Exercise and insulin: convergence or divergence at AS160 and TBC1D1? Exerc Sport Sci Rev 2009; 37:188-95.
74. Pehmoller C, Treebak JT, Birk JB, Chen S, Mackintosh C, Hardie DG, Richter EA, Wojtaszewski JF. Genetic disruption of AMPK signaling abolishes both contraction- and insulinstimulated TBC1D1 phosphorylation and 14-3-3 binding in mouse skeletal muscle. Am J Physiol Endocrinol Metab 2009; 297:E665-75.
75. Chen S, Wasserman DH, MacKintosh C, Sakamoto K. Mice with AS160/TBC1D4-Thr649Ala knockin mutation are glucose intolerant with reduced insulin sensitivity and altered GLUT4 trafficking. Cell Metab 2011;13:68-79.
76. Kramer HF, Witczak CA, Fujii N, Jessen N, Taylor EB, Arnolds DE, Sakamoto K, Hirshman MF, Goodyear LJ. Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR, and contraction in mouse skeletal muscle. Diabetes 2006;55:2067-76.
77. Treebak JT, Frosig C, Pehmoller C, Chen S, Maarbjerg SJ, Brandt N, MacKintosh C, Zierath JR, Hardie DG, Kiens B, Richter EA, Pilegaard H, Wojtaszewski JF. Potential role of TBC1D4 in enhanced post-exercise insulin action in human skeletal muscle. Diabetologia 2009;52:891-900.
78. Ducommun S, Wang HY, Sakamoto K, Mackintosh C, Chen S. Thr649Ala-AS160 knock-in mutation does not impair contraction/ AICAR-induced glucose transport in mouse muscle. Am J Physiol Endocrinol Metab 2012;302:E1036-43.
79. Chen S, Mackintosh C. Differential regulation of NHE1 phosphorylation and glucose uptake by inhibitors of the ERK pathway and p90RSK in 3T3-L1 adipocytes. Cell Signal 2009; 21:1984-93.
80. Geraghty KM, Chen S, Harthill JE, Ibrahim AF, Toth R, Morrice NA, Vandermoere F, Moorhead GB, Hardie DG, MacKintosh C. Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR. Biochem J 2007;407:231-41.
81. Vind BF, Pehmoller C, Treebak JT, Birk JB, Hey-Mogensen M, Beck-Nielsen H, Zierath JR, Wojtaszewski JF, Hojlund K. Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercisetraining. Diabetologia 2011;54:157-67.
82. Bouzakri K, Zachrisson A, Al-Khalili L, Zhang BB, Koistinen HA, Krook A, Zierath JR. siRNA-based gene silencing reveals specialized roles of IRS-1/Akt2 and IRS-2/Akt1 in glucose and lipid metabolism in human skeletal muscle. Cell Metab 2006;4:89-96.
83. Hoehn KL, Hohnen-Behrens C, Cederberg A, Wu LE, Turner N, Yuasa T, Ebina Y, James DE. IRS1-independent defects define major nodes of insulin resistance. Cell Metab 2008;7:421-33.
84. Shirakami A, Toyonaga T, Tsuruzoe K, Shirotani T, Matsumoto K, Yoshizato K, Kawashima J, Hirashima Y, Miyamura N, Kahn CR, Araki E. Heterozygous knockout of the IRS-1 gene in mice enhances obesity-linked insulin resistance: a possible model for the development of type 2 diabetes. J Endocrinol 2002;174:309-19.
85. Cleasby ME, Reinten TA, Cooney GJ, James DE, Kraegen EW. Functional studies of Akt isoform specificity in skeletal muscle in vivo: maintained insulin sensitivity despite reduced insulin receptor substrate-1 expression. Mol Endocrinol 2007; 21:215-28.
86. Gonzalez E, McGraw TE. Insulin signaling diverges into Aktdependent and -independent signals to regulate the recruitment/ docking and the fusion of GLUT4 vesicles to the plasma membrane. Mol Biol Cell 2006;17:4484-93.
87. Zaid H, Antonescu CN, Randhawa VK, Klip A. Insulin action on glucose transporters through molecular switches, tracks and tethers. Biochem J 2008;413:201-15.
88. JeBailey L, Rudich A, Huang X, Di Ciano-Oliveira C, Kapus A, Klip A. Skeletal muscle cells and adipocytes differ in their reliance on TC10 and Rac for insulin-induced actin remodeling. Mol Endocrinol 2004;18:359-72.
89. JeBailey L, Wanono O, Niu W, Roessler J, Rudich A, Klip A. Ceramide- and oxidant-induced insulin resistance involve loss of insulin-dependent Rac-activation and actin remodeling in muscle cells. Diabetes 2007;56:394-403.
90. Tsakiridis T, Vranic M, Klip A. Disassembly of the actin network inhibits insulin-dependent stimulation of glucose transport and prevents recruitment of glucose transporters to the plasma membrane. J Biol Chem 1994;269:29934-42.
91. Wang Q, Somwar R, Bilan PJ, Liu Z, Jin J, Woodgett JR, Klip A. Protein kinase B/Akt participates in GLUT4 translocation by insulin in L6 myoblasts. Mol Cell Biol 1999;19:4008-18.
92. Uberall F, Hellbert K, Kampfer S, Maly K, Villunger A, Spitaler M, Mwanjewe J, Baier-Bitterlich G, Baier G, Grunicke HH. Evidence that atypical protein kinase C-lambda and atypical protein kinase C-zeta participate in Ras-mediated reorganization of the F-actin cytoskeleton. J Cell Biol 1999;144:413-25.
93. Stone S, Abkevich V, Russell DL, Riley R, Timms K, Tran T, Trem D, Frank D, Jammulapati S, Neff CD, Iliev D, Gress R, He G, Frech GC, Adams TD, Skolnick MH, Lanchbury JS, Gutin A, Hunt SC, Shattuck D. TBC1D1 is a candidate for a severe obesity gene and evidence for a gene/gene interaction in obesity predisposition. Hum Mol Genet 2006;15:2709-20.
94. Meyre D, Farge M, Lecoeur C, Proenca C, Durand E, Allegaert F, Tichet J, Marre M, Balkau B, Weill J, Delplanque J, Froguel P. R125W coding variant in TBC1D1 confers risk for familial obesity and contributes to linkage on chromosome 4p14 in the French population. Hum Mol Genet 2008;17: 1798-802.
95. An D, Toyoda T, Taylor EB, Yu H, Fujii N, Hirshman MF, Goodyear LJ. TBC1D1 regulates insulin- and contraction-induced glucose transport in mouse skeletal muscle. Diabetes 2010;59:1358-65.
96. Roach WG, Chavez JA, Miinea CP, Lienhard GE. Substrate specificity and effect on GLUT4 translocation of the Rab GTPase-activating protein Tbc1d1. Biochem J 2007;403:353-8.
97. Chadt A, Leicht K, Deshmukh A, Jiang LQ, Scherneck S, Bernhardt U, Dreja T, Vogel H, Schmolz K, Kluge R, Zierath JR, Hultschig C, Hoeben RC, Schurmann A, Joost HG, Al-Hasani H. Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity. Nat Genet 2008;40:1354-9.
98. Taylor EB, An D, Kramer HF, Yu H, Fujii NL, Roeckl KS, Bowles N, Hirshman MF, Xie J, Feener EP, Goodyear LJ. Discovery of TBC1D1 as an insulin-, AICAR-, and contractionstimulated signaling nexus in mouse skeletal muscle. J Biol Chem 2008;283:9787-96.
99. Peck GR, Chavez JA, Roach WG, Budnik BA, Lane WS, Karlsson HK, Zierath JR, Lienhard GE. Insulin-stimulated phosphorylation of the Rab GTPase-activating protein TBC1D1 regulates GLUT4 translocation. J Biol Chem 2009;284:30016-23.
100. Barnes BR, Zierath JR. Role of AMP: activated protein kinase in the control of glucose homeostasis. Curr Mol Med 2005; 5:341-8.
101. Funai K, Cartee GD. Inhibition of contraction-stimulated AMP-activated protein kinase inhibits contraction-stimulated increases in PAS-TBC1D1 and glucose transport without altering PAS-AS160 in rat skeletal muscle. Diabetes 2009;58: 1096-104.
102. Vichaiwong K, Purohit S, An D, Toyoda T, Jessen N, Hirshman MF, Goodyear LJ. Contraction regulates site-specific phosphorylation of TBC1D1 in skeletal muscle. Biochem J 2010;431:311-20.
103. Yeh JI, Gulve EA, Rameh L, Birnbaum MJ. The effects of wortmannin on rat skeletal muscle. Dissociation of signaling pathways for insulin- and contraction-activated hexose transport. J Biol Chem 1995;270:2107-11.
104. Whitehead JP, Soos MA, Aslesen R, O'Rahilly S, Jensen J. Contraction inhibits insulin-stimulated insulin receptor substrate-1/2-associated phosphoinositide 3-kinase activity, but not protein kinase B activation or glucose uptake, in rat muscle. Biochem J 2000;349 Pt 3:775-81.
105. Lund S, Holman GD, Schmitz O, Pedersen O. Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. Proc Natl Acad Sci U S A 1995;92:5817-21.
106. Brozinick JT Jr, Birnbaum MJ. Insulin, but not contraction, activates Akt/PKB in isolated rat skeletal muscle. J Biol Chem 1998;273:14679-82.
107. Dumke CL, Wetter AC, Arias EB, Kahn CR, Cartee GD. Absence of insulin receptor substrate-1 expression does not alter GLUT1 or GLUT4 abundance or contraction-stimulated glucose uptake by mouse skeletal muscle. Horm Metab Res 2001; 33:696-700.
108. Sakamoto K, Arnolds DE, Fujii N, Kramer HF, Hirshman MF, Goodyear LJ. Role of Akt2 in contraction-stimulated cell signaling and glucose uptake in skeletal muscle. Am J Physiol Endocrinol Metab 2006;291:E1031-7.
109. Constable SH, Favier RJ, Cartee GD, Young DA, Holloszy JO. Muscle glucose transport: interactions of in vitro contractions, insulin, and exercise. J Appl Physiol 1988;64:2329-32.
110. Gao J, Ren J, Gulve EA, Holloszy JO. Additive effect of contractions and insulin on GLUT-4 translocation into the sarcolemma. J Appl Physiol 1994;77:1597-601.
111. Martin IK, Katz A, Wahren J. Splanchnic and muscle metabolism during exercise in NIDDM patients. Am J Physiol 1995; 269(3 Pt 1):E583-90.
112. Han X, Ploug T, Galbo H. Effect of diet on insulin- and contraction-mediated glucose transport and uptake in rat muscle. Am J Physiol 1995;269(3 Pt 2):R544-51.
113. King PA, Betts JJ, Horton ED, Horton ES. Exercise, unlike insulin, promotes glucose transporter translocation in obese Zucker rat muscle. Am J Physiol 1993;265(2 Pt 2):R447-52.
114. Brozinick JT Jr, Etgen GJ Jr, Yaspelkis BB 3rd, Ivy JL. Contraction-activated glucose uptake is normal in insulin-resistant muscle of the obese Zucker rat. J Appl Physiol 1992;73:382-7.
115. Bruss MD, Arias EB, Lienhard GE, Cartee GD. Increased phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle in response to insulin or contractile activity. Diabetes 2005;54:41-50.
116. Kramer HF, Taylor EB, Witczak CA, Fujii N, Hirshman MF, Goodyear LJ. Calmodulin-binding domain of AS160 regulates contraction- but not insulin-stimulated glucose uptake in skeletal muscle. Diabetes 2007;56:2854-62.
117. Frosig C, Pehmoller C, Birk JB, Richter EA, Wojtaszewski JF. Exercise-induced TBC1D1 Ser237 phosphorylation and 14-3-3 protein binding capacity in human skeletal muscle. J Physiol 2010;588(Pt 22):4539-48.
118. Lee-Young RS, Griffee SR, Lynes SE, Bracy DP, Ayala JE, Mc-Guinness OP, Wasserman DH. Skeletal muscle AMP-activated protein kinase is essential for the metabolic response to exercise in vivo. J Biol Chem 2009;284:23925-34.
119. Lefort N, St-Amand E, Morasse S, Cote CH, Marette A. The alpha-subunit of AMPK is essential for submaximal contraction-mediated glucose transport in skeletal muscle in vitro. Am J Physiol Endocrinol Metab 2008;295:E1447-54.
120. Merry TL, Steinberg GR, Lynch GS, McConell GK. Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK. Am J Physiol Endocrinol Metab 2010;298:E577-85.
121. Koh HJ, Toyoda T, Fujii N, Jung MM, Rathod A, Middelbeek RJ, Lessard SJ, Treebak JT, Tsuchihara K, Esumi H, Richter EA, Wojtaszewski JF, Hirshman MF, Goodyear LJ. Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle. Proc Natl Acad Sci U S A 2010;107:15541-6.
122. Arias EB, Kim J, Funai K, Cartee GD. Prior exercise increases phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle. Am J Physiol Endocrinol Metab 2007;292: E1191-200.
123. Funai K, Schweitzer GG, Castorena CM, Kanzaki M, Cartee GD. In vivo exercise followed by in vitro contraction additively elevates subsequent insulin-stimulated glucose transport by rat skeletal muscle. Am J Physiol Endocrinol Metab 2010;298:E999-1010.
124. Howlett KF, Mathews A, Garnham A, Sakamoto K. The effect of exercise and insulin on AS160 phosphorylation and 14-3-3 binding capacity in human skeletal muscle. Am J Physiol Endocrinol Metab 2008;294:E401-7.
125. Aschenbach WG, Suzuki Y, Breeden K, Prats C, Hirshman MF, Dufresne SD, Sakamoto K, Vilardo PG, Steele M, Kim JH, Jing SL, Goodyear LJ, DePaoli-Roach AA. The musclespecific protein phosphatase PP1G/R(GL)(G(M))is essential for activation of glycogen synthase by exercise. J Biol Chem 2001;276:39959-67.
126. Jensen J, Lai YC. Regulation of muscle glycogen synthase phosphorylation and kinetic properties by insulin, exercise, adrenaline and role in insulin resistance. Arch Physiol Biochem 2009;115:13-21.
127. Bouskila M, Hunter RW, Ibrahim AF, Delattre L, Peggie M, van Diepen JA, Voshol PJ, Jensen J, Sakamoto K. Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle. Cell Metab 2010;12:456-66.
128. McManus EJ, Sakamoto K, Armit LJ, Ronaldson L, Shpiro N, Marquez R, Alessi DR. Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis. EMBO J 2005;24:1571-83.
129. Polekhina G, Gupta A, Michell BJ, van Denderen B, Murthy S, Feil SC, Jennings IG, Campbell DJ, Witters LA, Parker MW, Kemp BE, Stapleton D. AMPK beta subunit targets metabolic stress sensing to glycogen. Curr Biol 2003;13:867-71.
130. McBride A, Ghilagaber S, Nikolaev A, Hardie DG. The glycogen-binding domain on the AMPK beta subunit allows the kinase to act as a glycogen sensor. Cell Metab 2009;9:23-34.
131. Bendayan M, Londono I, Kemp BE, Hardie GD, Ruderman N, Prentki M. Association of AMP-activated protein kinase subunits with glycogen particles as revealed in situ by immunoelectron microscopy. J Histochem Cytochem 2009;57:963-71.
132. Carling D, Hardie DG. The substrate and sequence specificity of the AMP-activated protein kinase. Phosphorylation of glycogen synthase and phosphorylase kinase. Biochim Biophys Acta 1989;1012:81-6.
133. Miyamoto L, Toyoda T, Hayashi T, Yonemitsu S, Nakano M, Tanaka S, Ebihara K, Masuzaki H, Hosoda K, Ogawa Y, Inoue G, Fushiki T, Nakao K. Effect of acute activation of 5'-AMPactivated protein kinase on glycogen regulation in isolated rat skeletal muscle. J Appl Physiol 2007;102:1007-13.
134. Wojtaszewski JF, Jorgensen SB, Hellsten Y, Hardie DG, 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 2002;51:284-92.
135. Jorgensen SB, Nielsen JN, Birk JB, Olsen GS, Viollet B, Andreelli F, Schjerling P, Vaulont S, Hardie DG, Hansen BF, Richter EA, Wojtaszewski JF. The alpha2-5'AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading. Diabetes 2004; 53:3074-81.
136. Bultot L, Guigas B, Von Wilamowitz-Moellendorff A, Maisin L, Vertommen D, Hussain N, Beullens M, Guinovart JJ, Foretz M, Viollet B, Sakamoto K, Hue L, Rider MH. AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase. Biochem J 2012;443:193-203.
137. Hunter RW, Treebak JT, Wojtaszewski JF, Sakamoto K. Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle. Diabetes 2011;60:766-74.
138. Jorgensen SB, Wojtaszewski JF, Viollet B, Andreelli F, Birk JB, Hellsten Y, Schjerling P, Vaulont S, Neufer PD, Richter EA, Pilegaard H. Effects of alpha-AMPK knockout on exerciseinduced gene activation in mouse skeletal muscle. FASEB J 2005;19:1146-8.
139. Steinberg GR, O'Neill HM, Dzamko NL, Galic S, Naim T, Koopman R, Jorgensen SB, Honeyman J, Hewitt K, Chen ZP, Schertzer JD, Scott JW, Koentgen F, Lynch GS, Watt MJ, van Denderen BJ, Campbell DJ, Kemp BE. Whole body deletion of AMP-activated protein kinase {beta}2 reduces muscle AMPK activity and exercise capacity. J Biol Chem 2010;285: 37198-209.
140. Mu J, Barton ER, Birnbaum MJ. Selective suppression of AMP-activated protein kinase in skeletal muscle: update on 'lazy mice'. Biochem Soc Trans 2003;31(Pt 1):236-41.
141. Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG. Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med 1990;322:223-8.
142. Funai K, Schweitzer GG, Sharma N, Kanzaki M, Cartee GD. Increased AS160 phosphorylation, but not TBC1D1 phosphorylation, with increased postexercise insulin sensitivity in rat skeletal muscle. Am J Physiol Endocrinol Metab 2009;297: E242-51.
143. Koshinaka K, Sano A, Howlett KF, Yamazaki T, Sasaki M, Sakamoto K, Kawanaka K. Effect of high-intensity intermittent swimming on postexercise insulin sensitivity in rat epitrochlearis muscle. Metabolism 2008;57:749-56.
144. Kim J, Solis RS, Arias EB, Cartee GD. Postcontraction insulin sensitivity: relationship with contraction protocol, glycogen concentration, and 5' AMP-activated protein kinase phosphorylation. J Appl Physiol 2004;96:575-83.
145. Jakobsen SN, Hardie DG, Morrice N, Tornqvist HE. 5'-AMPactivated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside. J Biol Chem 2001;276:46912-6.
146. Chopra I, Li HF, Wang H, Webster KA. Phosphorylation of the insulin receptor by AMP-activated protein kinase (AMPK) promotes ligand-independent activation of the insulin signalling pathway in rodent muscle. Diabetologia 2012;55:783-94.
147. Zakikhani M, Blouin MJ, Piura E, Pollak MN. Metformin and rapamycin have distinct effects on the AKT pathway and proliferation in breast cancer cells. Breast Cancer Res Treat 2010; 123:271-9.
148. Horike N, Takemori H, Katoh Y, Doi J, Min L, Asano T, Sun XJ, Yamamoto H, Kasayama S, Muraoka M, Nonaka Y, Okamoto M. Adipose-specific expression, phosphorylation of Ser794 in insulin receptor substrate-1, and activation in diabetic animals of salt-inducible kinase-2. J Biol Chem 2003; 278:18440-7.
149. Qiao LY, Zhande R, Jetton TL, Zhou G, Sun XJ. In vivo phosphorylation of insulin receptor substrate 1 at serine 789 by a novel serine kinase in insulin-resistant rodents. J Biol Chem 2002;277:26530-9.
150. Kimura N, Tokunaga C, Dalal S, Richardson C, Yoshino K, Hara K, Kemp BE, Witters LA, Mimura O, Yonezawa K. A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway. Genes Cells 2003;8:65-79.
151. Um SH, Frigerio F, Watanabe M, Picard F, Joaquin M, Sticker M, Fumagalli S, Allegrini PR, Kozma SC, Auwerx J, Thomas G. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 2004; 431:200-5.
152. Khamzina L, Veilleux A, Bergeron S, Marette A. Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance. Endocrinology 2005; 146:1473-81.
153. Dann SG, Selvaraj A, Thomas G. mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer. Trends Mol Med 2007;13:252-9.
154. Tremblay F, Brule S, Hee Um S, Li Y, Masuda K, Roden M, Sun XJ, Krebs M, Polakiewicz RD, Thomas G, Marette A. Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient-and obesity-induced insulin resistance. Proc Natl Acad Sci U S A 2007;104:14056-61.
155. Krebs M, Brunmair B, Brehm A, Artwohl M, Szendroedi J, Nowotny P, Roth E, Furnsinn C, Promintzer M, Anderwald C, Bischof M, Roden M. The mammalian target of rapamycin pathway regulates nutrient-sensitive glucose uptake in man. Diabetes 2007;56:1600-7.
156. Tremblay F, Krebs M, Dombrowski L, Brehm A, Bernroider E, Roth E, Nowotny P, Waldhausl W, Marette A, Roden M. Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability. Diabetes 2005;54:2674-84.
157. Glynn EL, Lujan HL, Kramer VJ, Drummond MJ, DiCarlo SE, Rasmussen BB. A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle. Appl Physiol Nutr Metab 2008;33:93-101.
158. Ju JS, Gitcho MA, Casmaer CA, Patil PB, Han DG, Spencer SA, Fisher JS. Potentiation of insulin-stimulated glucose transport by the AMP-activated protein kinase. Am J Physiol Cell Physiol 2007;292:C564-72.
159. Deshmukh AS, Treebak JT, Long YC, Viollet B, Wojtaszewski JF, Zierath JR. Role of adenosine 5'-monophosphate-activated protein kinase subunits in skeletal muscle mammalian target of rapamycin signaling. Mol Endocrinol 2008;22:1105-12.
160. Wang C, Mao X, Wang L, Liu M, Wetzel MD, Guan KL, Dong LQ, Liu F. Adiponectin sensitizes insulin signaling by reducing p70 S6 kinase-mediated serine phosphorylation of IRS-1. J Biol Chem 2007;282:7991-6.
161. Bluher M, Bullen JW Jr, Lee JH, Kralisch S, Fasshauer M, Kloting N, Niebauer J, Schon MR, Williams CJ, Mantzoros CS. Circulating adiponectin and expression of adiponectin receptors in human skeletal muscle: associations with metabolic parameters and insulin resistance and regulation by physical training. J Clin Endocrinol Metab 2006;91:2310-6.
162. Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev 2008;88: 1379-406.
163. Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG, Ramm G, Prelovsek O, Hohnen-Behrens C, Watt MJ, James DE, Kemp BE, Pedersen BK, Febbraio MA. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 2006;55:2688-97.
164. Geiger PC, Hancock C, Wright DC, Han DH, Holloszy JO. IL-6 increases muscle insulin sensitivity only at superphysiological levels. Am J Physiol Endocrinol Metab 2007;292: E1842-6.
165. Al-Khalili L, Bouzakri K, Glund S, Lonnqvist F, Koistinen HA, Krook A. Signaling specificity of interleukin-6 action on glucose and lipid metabolism in skeletal muscle. Mol Endocrinol 2006;20:3364-75.
166. Nieto-Vazquez I, Fernandez-Veledo S, de Alvaro C, Lorenzo M. Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle. Diabetes 2008;57:3211-21.
167. Benrick A, Wallenius V, Asterholm IW. Interleukin-6 mediates exercise-induced increase in insulin sensitivity in mice. Exp Physiol 2012;97:1224-35.
168. Fischer CP. Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev 2006;12:6-33.
169. Ellingsgaard H, Hauselmann I, Schuler B, Habib AM, Baggio LL, Meier DT, Eppler E, Bouzakri K, Wueest S, Muller YD, Hansen AM, Reinecke M, Konrad D, Gassmann M, Reimann F, Halban PA, Gromada J, Drucker DJ, Gribble FM, Ehses JA, Donath MY. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med 2011;17:1481-9.
170. Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, Wason CJ, Oberbach A, Jansson PA, Smith U, Kahn BB. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med 2006;354: 2552-63.
171. Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L, Kahn BB. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005;436:356-62.
172. Lee-Young RS, Ayala JE, Fueger PT, Mayes WH, Kang L, Wasserman DH. Obesity impairs skeletal muscle AMPK signaling during exercise: role of AMPKalpha2 in the regulation of exercise capacity in vivo. Int J Obes (Lond) 2011;35:982-9.
173. Steinberg GR, Smith AC, Van Denderen BJ, Chen Z, Murthy S, Campbell DJ, Heigenhauser GJ, Dyck DJ, Kemp BE. AMPactivated protein kinase is not down-regulated in human skeletal muscle of obese females. J Clin Endocrinol Metab 2004;89:4575-80.
174. Lee-Young RS, Canny BJ, Myers DE, McConell GK. AMPK activation is fiber type specific in human skeletal muscle: effects of exercise and short-term exercise training. J Appl Physiol 2009;107:283-9.
175. Jessen N, An D, Lihn AS, Nygren J, Hirshman MF, Thorell A, Goodyear LJ. Exercise increases TBC1D1 phosphorylation in human skeletal muscle. Am J Physiol Endocrinol Metab 2011; 301:E164-71.
176. Friedrichsen M, Mortensen B, Pehmoller C, Birk JB, Wojtaszewski JF. Exercise-induced AMPK activity in skeletal muscle: role in glucose uptake and insulin sensitivity. Mol Cell Endocrinol. Epub 2012 Jul 11. DOI: http://dx.doi.org/10.1016/ j.mce.2012.06.013.