AMPK and Exercise: Glucose Uptake and Insulin Sensitivity

다국어 초록 (Multilingual Abstract)

AMPK is an evolutionary conserved sensor of cellular energy status that is activated during exercise. Pharmacological activation of AMPK promotes glucose uptake, fatty acid oxidation, mitochondrial biogenesis, and insulin sensitivity; processes that are reduced in obesity and contribute to the development of insulin resistance. AMPK deficient mouse models have been used to provide direct genetic evidence either supporting or refuting a role for AMPK in regulating these processes. Exercise promotes glucose uptake by an insulin dependent mechanism involving AMPK. Exercise is important for improving insulin sensitivity; however,it is not known if AMPK is required for these improvements. Understanding how these metabolic processes are regulated is important for the development of new strategies that target obesity-induced insulin resistance. This review will discuss the involvement of AMPK in regulating skeletal muscle metabolism (glucose uptake, glycogen synthesis, and insulin sensitivity).

참고문헌 (Reference)

• 1 Bouzakri K, "siRNA-based gene silencing reveals specialized roles of IRS-1/Akt2 and IRS-2/Akt1 in glucose and lipid metabolism in human skeletal muscle" 4 : 89-96, 2006
• 2 Dann SG, "mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer" 13 : 252-259, 2007
• 3 Steinberg GR, "Whole body deletion of AMP-activated protein kinase {beta}2 reduces muscle AMPK activity and exercise capacity" 285 : 37198-37209, 2010
• 4 Steinberg GR, "Whole body deletion of AMP-activated protein kinase {beta}2 reduces muscle AMPK activity and exercise capacity" 285 : 37198-37209, 2010
• 5 Ducommun S, "Thr649Ala-AS160 knock-in mutation does not impair contraction/ AICAR-induced glucose transport in mouse muscle" 302 : E1036-E1043, 2012
• 6 Carling D, "The substrate and sequence specificity of the AMP-activated protein kinase. Phosphorylation of glycogen synthase and phosphorylase kinase" 1012 : 81-86, 1989
• 7 Aschenbach WG, "The musclespecific protein phosphatase PP1G/R(GL)(G(M))is essential for activation of glycogen synthase by exercise" 276 : 39959-39967, 2001
• 8 Krebs M, "The mammalian target of rapamycin pathway regulates nutrient-sensitive glucose uptake in man" 56 : 1600-1607, 2007
• 9 McBride A, "The glycogen- binding domain on the AMPK beta subunit allows the kinase to act as a glycogen sensor" 9 : 23-34, 2009
• 10 Yeh JI, "The effects of wortmannin on rat skeletal muscle. Dissociation of signaling pathways for insulin- and contraction-activated hexose transport" 270 : 2107-2111, 1995
• 11 Chen TC, "The effects of repeated maximal voluntary isokinetic eccentric exercise on recovery from muscle damage" 71 : 260-266, 2000
• 12 Thiebaud D, "The effect of graded doses of insulin on total glucose uptake, glucose oxidation, and glucose storage in man" 31 : 957-963, 1982
• 13 Howlett KF, "The effect of exercise and insulin on AS160 phosphorylation and 14-3-3 binding capacity in human skeletal muscle" 294 : E401-E407, 2008
• 14 Egan D, "The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR" 7 : 643-644, 2011
• 15 Jorgensen SB, "The alpha2-5’AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading" 53 : 3074-3081, 2004
• 16 Lefort N, "The alpha-subunit of AMPK is essential for submaximal contraction- mediated glucose transport in skeletal muscle in vitro" 295 : E1447-E1454, 2008
• 17 Hurley RL, "The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases" 280 : 29060-29066, 2005
• 18 Viollet B, "The AMPactivated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity" 111 : 91-98, 2003
• 19 Dasgupta B, "The AMPK beta2 subunit is required for energy homeostasis during metabolic stress" 32 : 2837-2848, 2012
• 20 Barnes BR, "The 5’-AMP-activated protein kinase gamma3 isoform has a key role in carbohydrate and lipid metabolism in glycolytic skeletal muscle" 279 : 38441-38447, 2004
• 21 Chadt A, "Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity" 40 : 1354-1359, 2008
• 22 An D, "TBC1D1 regulates insulin- and contraction-induced glucose transport in mouse skeletal muscle" 59 : 1358-1365, 2010
• 23 Stone S, "TBC1D1 is a candidate for a severe obesity gene and evidence for a gene/gene interaction in obesity predisposition" 15 : 2709-2720, 2006
• 24 DeFronzo RA, "Synergistic interaction between exercise and insulin on peripheral glucose uptake" 68 : 1468-1474, 1981
• 25 Koh HJ, "Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle" 107 : 15541-15546, 2010
• 26 Roach WG, "Substrate specificity and effect on GLUT4 translocation of the Rab GTPase- activating protein Tbc1d1" 403 : 353-358, 2007
• 27 Xiao B, "Structure of mammalian AMPK and its regulation by ADP" 472 : 230-233, 2011
• 28 Martin IK, "Splanchnic and muscle metabolism during exercise in NIDDM patients" 269 (269): E583-E590, 1995
• 29 Koh HJ, "Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3" 26 : 8217-8227, 2006
• 30 DeFronzo RA, "Skeletal muscle insulin resistance is the primary defect in type 2 diabetes" 32 (32): S157-S163, 2009
• 31 Merry TL, "Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK" 298 : E577-E585, 2010
• 32 JeBailey L, "Skeletal muscle cells and adipocytes differ in their reliance on TC10 and Rac for insulin-induced actin remodeling" 18 : 359-372, 2004
• 33 Thomson DM, "Skeletal muscle and heart LKB1 deficiency causes decreased voluntary running and reduced muscle mitochondrial marker enzyme expression in mice" 292 : E196-E202, 2007
• 34 Lee-Young RS, "Skeletal muscle AMP-activated protein kinase is essential for the metabolic response to exercise in vivo" 284 : 23925-23934, 2009
• 35 Al-Khalili L, "Signaling specificity of interleukin-6 action on glucose and lipid metabolism in skeletal muscle" 20 : 3364-3375, 2006
• 36 Yang Q, "Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes" 436 : 356-362, 2005
• 37 Mu J, "Selective suppression of AMP-activated protein kinase in skeletal muscle: update on ‘lazy mice’" 31 (31): 236-241, 2003
• 38 McManus EJ, "Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis" 24 : 1571-1583, 2005
• 39 Deshmukh AS, "Role of adenosine 5’-monophosphate-activated protein kinase subunits in skeletal muscle mammalian target of rapamycin signaling" 22 : 1105-1112, 2008
• 40 Sakamoto K, "Role of Akt2 in contraction-stimulated cell signaling and glucose uptake in skeletal muscle" 291 : E1031-E1037, 2006
• 41 Barnes BR, "Role of AMP: activated protein kinase in the control of glucose homeostasis" 5 : 341-348, 2005
• 42 Graham TE, "Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects" 354 : 2552-2563, 2006
• 43 Jensen J, "Regulation of muscle glycogen synthase phosphorylation and kinetic properties by insulin, exercise, adrenaline and role in insulin resistance" 115 : 13-21, 2009
• 44 Geraghty KM, "Regulation of multisite phosphorylation and 14- 3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR" 407 : 231-241, 2007
• 45 Dyck JR, "Regulation of 5’-AMP-activated protein kinase activity by the noncatalytic beta and gamma subunits" 271 : 17798-17803, 1996
• 46 Beck Jorgensen S, "Reduced AMP-activated protein kinase activity in mouse skeletal muscle does not exacerbate the development of insulin resistance with obesity" 52 : 2395-2404, 2009
• 47 Meyre D, "R125W coding variant in TBC1D1 confers risk for familial obesity and contributes to linkage on chromosome 4p14 in the French population" 17 : 1798-1802, 2008
• 48 Shulman GI, "Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy" 322 : 223-228, 1990
• 49 Wang Q, "Protein kinase B/Akt participates in GLUT4 translocation by insulin in L6 myoblasts" 19 : 4008-4018, 1999
• 50 Arias EB, "Prior exercise increases phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle" 292 : E1191-E1200, 2007
• 51 Ju JS, "Potentiation of insulin-stimulated glucose transport by the AMP-activated protein kinase" 292 : C564-C572, 2007
• 52 Treebak JT, "Potential role of TBC1D4 in enhanced post-exercise insulin action in human skeletal muscle" 52 : 891-900, 2009
• 53 Rasmussen BB, "Postexercise recovery of skeletal muscle malonyl-CoA, acetyl-CoA carboxylase, and AMP-activated protein kinase" 85 : 1629-1634, 1998
• 54 Kim J, "Postcontraction insulin sensitivity: relationship with contraction protocol, glycogen concentration, and 5’ AMP-activated protein kinase phosphorylation" 96 : 575-583, 2004
• 55 Viollet B, "Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models" 31 : 216-219, 2003
• 56 Chopra I, "Phosphorylation of the insulin receptor by AMP-activated protein kinase (AMPK) promotes ligand-independent activation of the insulin signalling pathway in rodent muscle" 55 : 783-794, 2012
• 57 Winder WW, "Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A" 82 : 219-225, 1997
• 58 Sarbassov DD, "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex" 307 : 1098-1101, 2005
• 59 Tremblay F, "Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability" 54 : 2674-2684, 2005
• 60 Nilsson EC, "Opposite transcriptional regulation in skeletal muscle of AMPactivated protein kinase gamma3 R225Q transgenic versus knock-out mice" 281 : 7244-7252, 2006
• 61 Lee-Young RS, "Obesity impairs skeletal muscle AMPK signaling during exercise: role of AMPKalpha2 in the regulation of exercise capacity in vivo" 35 : 982-989, 2011
• 62 Gollob MH, "Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy" 104 : 3030-3033, 2001
• 63 Crawford SA, "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" 53 : 1986-1997, 2010
• 64 Constable SH, "Muscle glucose transport: interactions of in vitro contractions, insulin, and exercise" 64 : 2329-2332, 1988
• 65 Ishikura S, "Muscle cells engage Rab8A and myosin Vb in insulin-dependent GLUT4 translocation" 295 : C1016-C1025, 2008
• 66 Pedersen BK, "Muscle as an endocrine organ: focus on muscle-derived interleukin-6" 88 : 1379-1406, 2008
• 67 Hunter RW, "Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle" 60 : 766-774, 2011
• 68 Chen S, "Mice with AS160/TBC1D4-Thr649Ala knockin mutation are glucose intolerant with reduced insulin sensitivity and altered GLUT4 trafficking" 13 : 68-79, 2011
• 69 Zakikhani M, "Metformin and rapamycin have distinct effects on the AKT pathway and proliferation in breast cancer cells" 123 : 271-279, 2010
• 70 Hayashi T, "Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism" 49 : 527-531, 2000
• 71 Alessi DR, "Mechanism of activation of protein kinase B by insulin and IGF-1" 15 : 6541-6551, 1996
• 72 Woods A, "LKB1 is the upstream kinase in the AMP-activated protein kinase cascade" 13 : 2004-2008, 2003
• 73 Jorgensen SB, "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" 279 : 1070-1079, 2004
• 74 Wojtaszewski JF, "Isoform-specific and exercise intensity-dependent activation of 5’-AMP-activated protein kinase in human skeletal muscle" 528 (528): 221-226, 2000
• 75 Sanders MJ, "Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade" 403 : 139-148, 2007
• 76 Benrick A, "Interleukin-6 mediates exercise-induced increase in insulin sensitivity in mice" 97 : 1224-1235, 2012
• 77 Fischer CP, "Interleukin-6 in acute exercise and training: what is the biological relevance?" 12 : 6-33, 2006
• 78 Ellingsgaard H, "Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells" 17 : 1481-1489, 2011
• 79 Carey AL, "Interleukin- 6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase" 55 : 2688-2697, 2006
• 80 Canto C, "Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle" 11 : 213-219, 2010
• 81 Peck GR, "Insulin-stimulated phosphorylation of the Rab GTPase-activating protein TBC1D1 regulates GLUT4 translocation" 284 : 30016-30023, 2009
• 82 Sano H, "Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation" 278 : 14599-14602, 2003
• 83 Brozinick JT Jr, "Insulin, but not contraction, activates Akt/PKB in isolated rat skeletal muscle" 273 : 14679-14682, 1998
• 84 Saltiel AR, "Insulin signalling and the regulation of glucose and lipid metabolism" 414 : 799-806, 2001
• 85 Gonzalez E, "Insulin signaling diverges into Aktdependent and -independent signals to regulate the recruitment/ docking and the fusion of GLUT4 vesicles to the plasma membrane" 17 : 4484-4493, 2006
• 86 Zaid H, "Insulin action on glucose transporters through molecular switches, tracks and tethers" 413 : 201-215, 2008
• 87 Funai K, "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" 58 : 1096-1104, 2009
• 88 Bruss MD, "Increased phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle in response to insulin or contractile activity" 54 : 41-50, 2005
• 89 Khamzina L, "Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance" 146 : 1473-1481, 2005
• 90 Funai K, "Increased AS160 phosphorylation, but not TBC1D1 phosphorylation, with increased postexercise insulin sensitivity in rat skeletal muscle" 297 : E242-E251, 2009
• 91 Winder WW, "Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise" 270 (270): E299-E304, 1996
• 92 Qiao LY, "In vivo phosphorylation of insulin receptor substrate 1 at serine 789 by a novel serine kinase in insulin-resistant rodents" 277 : 26530-26539, 2002
• 93 Funai K, "In vivo exercise followed by in vitro contraction additively elevates subsequent insulin-stimulated glucose transport by rat skeletal muscle" 298 : E999-E1010, 2010
• 94 Vind BF, "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" 54 : 157-167, 2011
• 95 Gollob MH, "Identification of a gene responsible for familial Wolff-Parkinson-White syndrome" 344 : 1823-1831, 2001
• 96 Tremblay F, "Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance" 104 : 14056-14061, 2007
• 97 Hoehn KL, "IRS1-independent defects define major nodes of insulin resistance" 7 : 421-433, 2008
• 98 Geiger PC, "IL-6 increases muscle insulin sensitivity only at superphysiological levels" 292 : E1842-E1846, 2007
• 99 Shirakami A, "Heterozygous knockout of the IRS-1 gene in mice enhances obesity-linked insulin resistance: a possible model for the development of type 2 diabetes" 174 : 309-319, 2002
• 100 Wojtaszewski JF, "Glycogen-dependent effects of 5-aminoimidazole-4- carboxamide (AICA)-riboside on AMP-activated protein kinase and glycogen synthase activities in rat skeletal muscle" 51 : 284-292, 2002
• 101 Quinn JM, "Germline deletion of AMP-activated protein kinase beta subunits reduces bone mass without altering osteoclast differentiation or function" 24 : 275-285, 2010
• 102 Pehmoller C, "Genetic disruption of AMPK signaling abolishes both contraction- and insulinstimulated TBC1D1 phosphorylation and 14-3-3 binding in mouse skeletal muscle" 297 : E665-E675, 2009
• 103 Mortensen B, "Genetic and metabolic effects on skeletal muscle AMPK in young and older twins" 297 : E956-E964, 2009
• 104 Costford SR, "Gain-of-function R225W mutation in human AMPKgamma( 3) causing increased glycogen and decreased triglyceride in skeletal muscle" 2 : e903-, 2007
• 105 Cleasby ME, "Functional studies of Akt isoform specificity in skeletal muscle in vivo: maintained insulin sensitivity despite reduced insulin receptor substrate-1 expression" 21 : 215-228, 2007
• 106 Mahlapuu M, "Expression profiling of the gamma-subunit isoforms of AMP-activated protein kinase suggests a major role for gamma3 in white skeletal muscle" 286 : E194-E200, 2004
• 107 Chen Z, "Expression of the AMP-activated protein kinase beta1 and beta2 subunits in skeletal muscle" 460 : 343-348, 1999
• 108 Frosig C, "Exercise-induced TBC1D1 Ser237 phosphorylation and 14- 3-3 protein binding capacity in human skeletal muscle" 588 (588): 4539-4548, 2010
• 109 Friedrichsen M, "Exercise-induced AMPK activity in skeletal muscle: role in glucose uptake and insulin sensitivity" 2012
• 110 King PA, "Exercise, unlike insulin, promotes glucose transporter translocation in obese Zucker rat muscle" 265 (265): R447-R452, 1993
• 111 Fujii N, "Exercise induces isoform-specific increase in 5’AMP-activated protein kinase activity in human skeletal muscle" 273 : 1150-1155, 2000
• 112 Jessen N, "Exercise increases TBC1D1 phosphorylation in human skeletal muscle" 301 : E164-E171, 2011
• 113 Cartee GD, "Exercise and insulin: convergence or divergence at AS160 and TBC1D1?" 37 : 188-195, 2009
• 114 Uberall F, "Evidence that atypical protein kinase C-lambda and atypical protein kinase C-zeta participate in Ras-mediated reorganization of the F-actin cytoskeleton" 144 : 413-425, 1999
• 115 Hayashi T, "Evidence for 5’ AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport" 47 : 1369-1373, 1998
• 116 Murphy RM, "Enhanced technique to measure proteins in single segments of human skeletal muscle fibers: fiber-type dependence of AMPK-alpha1 and -beta1" 110 : 820-825, 2011
• 117 Sahlin K, "Energy supply and muscle fatigue in humans" 162 : 261-266, 1998
• 118 Hutber CA, "Electrical stimulation inactivates muscle acetyl-CoA carboxylase and increases AMP-activated protein kinase" 272 (272): E262-E266, 1997
• 119 Jorgensen SB, "Effects of alpha-AMPK knockout on exerciseinduced gene activation in mouse skeletal muscle" 19 : 1146-1148, 2005
• 120 Ihlemann J, "Effect of tension on contraction-induced glucose transport in rat skeletal muscle" 277 (277): E208-E214, 1999
• 121 Koshinaka K, "Effect of high-intensity intermittent swimming on postexercise insulin sensitivity in rat epitrochlearis muscle" 57 : 749-756, 2008
• 122 Rasmussen BB, "Effect of exercise intensity on skeletal muscle malonyl-CoA and acetyl-CoA carboxylase" 83 : 1104-1109, 1997
• 123 Chen ZP, "Effect of exercise intensity on skeletal muscle AMPK signaling in humans" 52 : 2205-2212, 2003
• 124 Han X, "Effect of diet on insulin- and contraction- mediated glucose transport and uptake in rat muscle" 269 (269): R544-R551, 1995
• 125 Miyamoto L, "Effect of acute activation of 5’-AMPactivated protein kinase on glycogen regulation in isolated rat skeletal muscle" 102 : 1007-1013, 2007
• 126 Nieto-Vazquez I, "Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle" 57 : 3211-3221, 2008
• 127 Kramer HF, "Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR, and contraction in mouse skeletal muscle" 55 : 2067-2076, 2006
• 128 Taylor EB, "Discovery of TBC1D1 as an insulin-, AICAR-, and contractionstimulated signaling nexus in mouse skeletal muscle" 283 : 9787-9796, 2008
• 129 Tsakiridis T, "Disassembly of the actin network inhibits insulin-dependent stimulation of glucose transport and prevents recruitment of glucose transporters to the plasma membrane" 269 : 29934-29942, 1994
• 130 Chen S, "Differential regulation of NHE1 phosphorylation and glucose uptake by inhibitors of the ERK pathway and p90RSK in 3T3-L1 adipocytes" 21 : 1984-1993, 2009
• 131 Sakamoto K, "Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction" 24 : 1810-1820, 2005
• 132 Vavvas D, "Contraction-induced changes in acetyl-CoA carboxylase and 5’-AMP-activated kinase in skeletal muscle" 272 : 13255-13261, 1997
• 133 Brozinick JT Jr, "Contraction- activated glucose uptake is normal in insulin-resistant muscle of the obese Zucker rat" 73 : 382-387, 1992
• 134 Lund S, "Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin" 92 : 5817-5821, 1995
• 135 Vichaiwong K, "Contraction regulates site-specific phosphorylation of TBC1D1 in skeletal muscle" 431 : 311-320, 2010
• 136 Whitehead JP, "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" 349 (349): 775-781, 2000
• 137 Arad M, "Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy" 109 : 357-362, 2002
• 138 Hawley SA, "Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade" 2 : 28-, 2003
• 139 Chen S, "Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators" 409 : 449-459, 2008
• 140 Yu H, "Cloning and characterization of mouse 5’-AMP-activated protein kinase gamma3 subunit" 286 : C283-C292, 2004
• 141 Bluher M, "Circulating adiponectin and expression of adiponectin receptors in human skeletal muscle: associations with metabolic parameters and insulin resistance and regulation by physical training" 91 : 2310-2316, 2006
• 142 Hawley SA, "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" 271 : 27879-27887, 1996
• 143 Alessi DR, "Characterization of a 3-phosphoinositide- dependent protein kinase which phosphorylates and activates protein kinase Balpha" 7 : 261-269, 1997
• 144 Cheung PC, "Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding" 346 (346): 659-669, 2000
• 145 JeBailey L, "Ceramide- and oxidant-induced insulin resistance involve loss of insulin-dependent Rac-activation and actin remodeling in muscle cells" 56 : 394-403, 2007
• 146 Hawley SA, "Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase" 2 : 9-19, 2005
• 147 Kramer HF, "Calmodulin-binding domain of AS160 regulates contraction- but not insulin-stimulated glucose uptake in skeletal muscle" 56 : 2854-2862, 2007
• 148 Woods A, "Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMPactivated protein kinase in mammalian cells" 2 : 21-33, 2005
• 149 Bendayan M, "Association of AMP-activated protein kinase subunits with glycogen particles as revealed in situ by immunoelectron microscopy" 57 : 963-971, 2009
• 150 Bouskila M, "Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle" 12 : 456-466, 2010
• 151 Horike N, "Adipose-specific expression, phosphorylation of Ser794 in insulin receptor substrate-1, and activation in diabetic animals of salt-inducible kinase-2" 278 : 18440-18447, 2003
• 152 Wang C, "Adiponectin sensitizes insulin signaling by reducing p70 S6 kinase-mediated serine phosphorylation of IRS-1" 282 : 7991-7996, 2007
• 153 Gao J, "Additive effect of contractions and insulin on GLUT-4 translocation into the sarcolemma" 77 : 1597-1601, 1994
• 154 Kennedy JW, "Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes" 48 : 1192-1197, 1999
• 155 Dumke CL, "Absence of insulin receptor substrate-1 expression does not alter GLUT1 or GLUT4 abundance or contraction-stimulated glucose uptake by mouse skeletal muscle" 33 : 696-700, 2001
• 156 Um SH, "Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity" 431 : 200-205, 2004
• 157 Fujii N, "Ablation of AMPactivated protein kinase alpha2 activity exacerbates insulin resistance induced by high-fat feeding of mice" 57 : 2958-2966, 2008
• 158 Luptak I, "Aberrant activation of AMPactivated protein kinase remodels metabolic network in favor of cardiac glycogen storage" 117 : 1432-1439, 2007
• 159 Kramer HF, "AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle" 281 : 31478-31485, 2006
• 160 Steinberg GR, "AMPactivated protein kinase is not down-regulated in human skeletal muscle of obese females" 89 : 4575-4580, 2004
• 161 Dzamko N, "AMPK-independent pathways regulate skeletal muscle fatty acid oxidation" 586 : 5819-5831, 2008
• 162 Oakhill JS, "AMPK is a direct adenylate charge-regulated protein kinase" 332 : 1433-1435, 2011
• 163 Dzamko N, "AMPK beta1 deletion reduces appetite, preventing obesity and hepatic insulin resistance" 285 : 115-122, 2010
• 164 Polekhina G, "AMPK beta subunit targets metabolic stress sensing to glycogen" 13 : 867-871, 2003
• 165 Lee-Young RS, "AMPK activation is fiber type specific in human skeletal muscle: effects of exercise and short-term exercise training" 107 : 283-289, 2009
• 166 Bultot L, "AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase" 443 : 193-203, 2012
• 167 Fujii N, "AMP-activated protein kinase alpha2 activity is not essential for contraction- and hyperosmolarityinduced glucose transport in skeletal muscle" 280 : 39033-39041, 2005
• 168 O’Neill HM, "AMP-activated protein kinase (AMPK) beta1beta2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise" 108 : 16092-16097, 2011
• 169 Mu J, "A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle" 7 : 1085-1094, 2001
• 170 Kimura N, "A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway" 8 : 65-79, 2003
• 171 Milan D, "A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle" 288 : 1248-1251, 2000
• 172 Glynn EL, "A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle" 33 : 93-101, 2008
• 173 Wojtaszewski JF, "5’AMP activated protein kinase expression in human skeletal muscle: effects of strength training and type 2 diabetes" 564 (564): 563-573, 2005
• 174 Jakobsen SN, "5’-AMPactivated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4- carboxamide riboside" 276 : 46912-46916, 2001
• 175 Barnes BR, "5’-AMP-activated protein kinase regulates skeletal muscle glycogen content and ergogenics" 19 : 773-779, 2005
• 176 Frosig C, "5’-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle" 286 : E411-E417, 2004