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Regulation of Carbohydrate Metabolism, Lipid Metabolism, and Protein Metabolism by AMPK

  • Yeliz Angin
  • Christophe Beauloye
  • Sandrine Horman
  • Luc Bertrand
Chapter
Part of the Experientia Supplementum book series (EXS, volume 107)

Abstract

This chapter summarizes AMPK function in the regulation of substrate and energy metabolism with the main emphasis on carbohydrate and lipid metabolism, protein turnover, mitochondrial biogenesis, and whole-body energy homeostasis. AMPK acts as whole-body energy sensor and integrates different signaling pathway to meet both cellular and body energy requirements while inhibiting energy-consuming processes but also activating energy-producing ones. AMPK mainly promotes glucose and fatty acid catabolism, whereas it prevents protein, glycogen, and fatty acid synthesis.

Keywords

AMPK Glucose metabolism Lipid metabolism Protein synthesis Insulin sensitivity Mitochondrial biogenesis 

References

  1. Abu-Elheiga L, Jayakumar A, Baldini A, Chirala SS, Wakil SJ (1995) Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence for two isoforms. Proc Natl Acad Sci USA 92(9):4011–4015, Pubmed Central PMCID: 42092PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alzamora R, Gong F, Rondanino C, Lee JK, Smolak C, Pastor-Soler NM et al (2010) AMP-activated protein kinase inhibits KCNQ1 channels through regulation of the ubiquitin ligase Nedd4-2 in renal epithelial cells. Am J Physiol Renal Physiol 299(6):F1308–F1319, Pubmed Central PMCID: 3006313PubMedPubMedCentralCrossRefGoogle Scholar
  3. An H, He L (2016) Current understanding of metformin effect on the control of hyperglycemia in diabetes. J Endocrinol 228(3):R97–R106, Epub 2016/01/09. engPubMedPubMedCentralCrossRefGoogle Scholar
  4. An D, Kewalramani G, Qi D, Pulinilkunnil T, Ghosh S, Abrahani A et al (2005) beta-Agonist stimulation produces changes in cardiac AMPK and coronary lumen LPL only during increased workload. Am J Physiol Endocrinol Metab 288(6):E1120–E1127, Epub 2005/02/03. engPubMedCrossRefGoogle Scholar
  5. Awazawa M, Ueki K, Inabe K, Yamauchi T, Kaneko K, Okazaki Y et al (2009) Adiponectin suppresses hepatic SREBP1c expression in an AdipoR1/LKB1/AMPK dependent pathway. Biochem Biophys Res Commun 382(1):51–56, Epub 2009/03/04. engPubMedCrossRefGoogle Scholar
  6. Bando H, Atsumi T, Nishio T, Niwa H, Mishima S, Shimizu C et al (2005) Phosphorylation of the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase/PFKFB3 family of glycolytic regulators in human cancer. Clin Cancer Res 11(16):5784–5792, Epub 2005/08/24. engPubMedCrossRefGoogle Scholar
  7. Bar-Peled L, Sabatini DM (2014) Regulation of mTORC1 by amino acids. Trends Cell Biol 24(7):400–406, Pubmed Central PMCID: 4074565PubMedPubMedCentralCrossRefGoogle Scholar
  8. Baskin KK, Taegtmeyer H (2011) AMP-activated protein kinase regulates E3 ligases in rodent heart. Circ Res 109(10):1153–1161, Pubmed Central PMCID: 3254015PubMedPubMedCentralCrossRefGoogle Scholar
  9. Beauloye C, Marsin AS, Bertrand L, Vanoverschelde JL, Rider MH, Hue L (2002) The stimulation of heart glycolysis by increased workload does not require AMP-activated protein kinase but a wortmannin-sensitive mechanism. FEBS Lett 531(2):324–328PubMedCrossRefGoogle Scholar
  10. Beg ZH, Allmann DW, Gibson DM (1973) Modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and with protein fractions of rat liver cytosol. Biochem Biophys Res Commun 54(4):1362–1369PubMedCrossRefGoogle Scholar
  11. Beg ZH, Stonik JA, Brewer HB Jr (1979) Characterization and regulation of reductase kinase, a protein kinase that modulates the enzymic activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Proc Natl Acad Sci USA 76(9):4375–4379, Pubmed Central PMCID: 411577PubMedPubMedCentralCrossRefGoogle Scholar
  12. Bergeron R, Russell RR 3rd, Young LH, Ren JM, Marcucci M, Lee A et al (1999) Effect of AMPK activation on muscle glucose metabolism in conscious rats. Am J Physiol 276(5 Pt 1):E938–E944PubMedGoogle Scholar
  13. Bhalla V, Oyster NM, Fitch AC, Wijngaarden MA, Neumann D, Schlattner U et al (2006) AMP-activated kinase inhibits the epithelial Na+ channel through functional regulation of the ubiquitin ligase Nedd4-2. J Biol Chem 281(36):26159–26169PubMedCrossRefGoogle Scholar
  14. Bickerton AS, Roberts R, Fielding BA, Hodson L, Blaak EE, Wagenmakers AJ et al (2007) Preferential uptake of dietary fatty acids in adipose tissue and muscle in the postprandial period. Diabetes 56(1):168–176, Epub 2006/12/29. engPubMedCrossRefGoogle Scholar
  15. Bolster DR, Crozier SJ, Kimball SR, Jefferson LS (2002) AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem 277(27):23977–23980PubMedCrossRefGoogle Scholar
  16. Browne GJ, Finn SG, Proud CG (2004) Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398. J Biol Chem 279(13):12220–12231PubMedCrossRefGoogle Scholar
  17. Bruce CR, Hoy AJ, Turner N, Watt MJ, Allen TL, Carpenter K et al (2009) Overexpression of carnitine palmitoyltransferase-1 in skeletal muscle is sufficient to enhance fatty acid oxidation and improve high-fat diet-induced insulin resistance. Diabetes 58(3):550–558, Pubmed Central PMCID: 2646053, Epub 2008/12/17. engPubMedPubMedCentralCrossRefGoogle Scholar
  18. Bruss MD, Arias EB, Lienhard GE, Cartee GD (2005) Increased phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle in response to insulin or contractile activity. Diabetes 54(1):41–50PubMedCrossRefGoogle Scholar
  19. Canto C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC et al (2009) AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 458(7241):1056–1060, Pubmed Central PMCID: 3616311PubMedPubMedCentralCrossRefGoogle Scholar
  20. Carling D, Zammit VA, Hardie DG (1987) A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett 223(2):217–222PubMedCrossRefGoogle Scholar
  21. Carling D, Clarke PR, Zammit VA, Hardie DG (1989) Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities. Eur J Biochem/FEBS 186(1-2):129–136CrossRefGoogle Scholar
  22. Carlson CA, Kim KH (1973) Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. J Biol Chem 248(1):378–380PubMedGoogle Scholar
  23. Chen S, Murphy J, Toth R, Campbell DG, Morrice NA, Mackintosh C (2008) Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators. Biochem J 409(2):449–459, Epub 2007/11/13. engPubMedCrossRefGoogle Scholar
  24. Chopra I, Li HF, Wang H, Webster KA (2012) Phosphorylation of the insulin receptor by AMP-activated protein kinase (AMPK) promotes ligand-independent activation of the insulin signalling pathway in rodent muscle. Diabetologia 55(3):783–794, Pubmed Central PMCID: 4648248PubMedCrossRefGoogle Scholar
  25. Coburn CT, Knapp FF Jr, Febbraio M, Beets AL, Silverstein RL, Abumrad NA (2000) Defective uptake and utilization of long chain fatty acids in muscle and adipose tissues of CD36 knockout mice. J Biol Chem 275(42):32523–32529, Epub 2000/07/27. engPubMedCrossRefGoogle Scholar
  26. Coven DL, Hu X, Cong L, Bergeron R, Shulman GI, Hardie DG et al (2003) Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise. Am J Physiol Endocrinol Metab 285(3):E629–E636, Epub 2003/05/22. engPubMedCrossRefGoogle Scholar
  27. De Duve C, Wattiaux R (1966) Functions of lysosomes. Annu Rev Physiol 28:435–492PubMedCrossRefGoogle Scholar
  28. Destefano MA, Jacinto E (2013) Regulation of insulin receptor substrate-1 by mTORC2 (mammalian target of rapamycin complex 2). Biochem Soc Trans 41(4):896–901, Epub 2013/07/19. engPubMedPubMedCentralCrossRefGoogle Scholar
  29. Dubbelhuis PF, Meijer AJ (2002) Hepatic amino acid-dependent signaling is under the control of AMP-dependent protein kinase. FEBS Lett 521(1-3):39–42PubMedCrossRefGoogle Scholar
  30. Dunlop EA, Tee AR (2013) The kinase triad, AMPK, mTORC1 and ULK1, maintains energy and nutrient homoeostasis. Biochem Soc Trans 41(4):939–943PubMedCrossRefGoogle Scholar
  31. Eberle D, Hegarty B, Bossard P, Ferre P, Foufelle F (2004) SREBP transcription factors: master regulators of lipid homeostasis. Biochimie 86(11):839–848PubMedCrossRefGoogle Scholar
  32. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W et al (2011) Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331(6016):456–461, Pubmed Central PMCID: 3030664PubMedCrossRefGoogle Scholar
  33. Ferrer A, Caelles C, Massot N, Hegardt FG (1985) Activation of rat liver cytosolic 3-hydroxy-3-methylglutaryl coenzyme A reductase kinase by adenosine 5′-monophosphate. Biochem Biophys Res Commun 132(2):497–504PubMedCrossRefGoogle Scholar
  34. Foretz M, Hebrard S, Leclerc J, Zarrinpashneh E, Soty M, Mithieux G et al (2010) Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest 120(7):2355–2369, Pubmed Central PMCID: 2898585PubMedPubMedCentralCrossRefGoogle Scholar
  35. Geraghty KM, Chen S, Harthill JE, Ibrahim AF, Toth R, Morrice NA et al (2007) Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR. Biochem J 407(2):231–241, Pubmed Central PMCID: 2049023PubMedPubMedCentralCrossRefGoogle Scholar
  36. Ginion A, Auquier J, Benton CR, Mouton C, Vanoverschelde JL, Hue L et al (2011) Inhibition of the mTOR/p70S6K pathway is not involved in the insulin-sensitizing effect of AMPK on cardiac glucose uptake. Am J Physiol Heart Circ Physiol 301(2):H469–H477PubMedCrossRefGoogle Scholar
  37. Glatz JF, Luiken JJ, Bonen A (2010) Membrane fatty acid transporters as regulators of lipid metabolism: implications for metabolic disease. Physiol Rev 90(1):367–417PubMedCrossRefGoogle Scholar
  38. Guo L, Zheng X, Liu J, Yin Z (2016) Geniposide suppresses hepatic glucose production via AMPK in HepG2 cells. Biol Pharm Bull 39:484–491, Epub 2016/02/03. EngPubMedCrossRefGoogle Scholar
  39. Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS et al (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30(2):214–226, Pubmed Central PMCID: 2674027PubMedPubMedCentralCrossRefGoogle Scholar
  40. Habets DD, Coumans WA, Voshol PJ, den Boer MA, Febbraio M, Bonen A et al (2007) AMPK-mediated increase in myocardial long-chain fatty acid uptake critically depends on sarcolemmal CD36. Biochem Biophys Res Commun 355(1):204–210PubMedCrossRefGoogle Scholar
  41. Habets DD, Coumans WA, El Hasnaoui M, Zarrinpashneh E, Bertrand L, Viollet B et al (2009) Crucial role for LKB1 to AMPKalpha2 axis in the regulation of CD36-mediated long-chain fatty acid uptake into cardiomyocytes. Biochim Biophys Acta 1791(3):212–219PubMedCrossRefGoogle Scholar
  42. Halse R, Fryer LG, McCormack JG, Carling D, Yeaman SJ (2003) Regulation of glycogen synthase by glucose and glycogen: a possible role for AMP-activated protein kinase. Diabetes 52(1):9–15, Epub 2002/12/28. engPubMedCrossRefGoogle Scholar
  43. Handschin C, Spiegelman BM (2006) Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 27(7):728–735PubMedCrossRefGoogle Scholar
  44. Hardie DG, Pan DA (2002) Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase. Biochem Soc Trans 30(Pt 6):1064–1070, Epub 2002/11/21. engPubMedCrossRefGoogle Scholar
  45. Hardie DG, Hawley SA, Scott JW (2006) AMP-activated protein kinase – development of the energy sensor concept. J Physiol 574(Pt 1):7–15, Pubmed Central PMCID: 1817788PubMedPubMedCentralCrossRefGoogle Scholar
  46. Hayashi T, Hirshman MF, Kurth EJ, Winder WW, Goodyear LJ (1998) Evidence for 5′ AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes 47(8):1369–1373PubMedGoogle Scholar
  47. Holmes B, Dohm GL (2004) Regulation of GLUT4 gene expression during exercise. Med Sci Sports Exerc 36(7):1202–1206, Epub 2004/07/06. engPubMedCrossRefGoogle Scholar
  48. Holmes BF, Sparling DP, Olson AL, Winder WW, Dohm GL (2005) Regulation of muscle GLUT4 enhancer factor and myocyte enhancer factor 2 by AMP-activated protein kinase. Am J Physiol Endocrinol Metab 289(6):E1071–E1076, Epub 2005/08/18. engPubMedCrossRefGoogle Scholar
  49. Horman S, Browne G, Krause U, Patel J, Vertommen D, Bertrand L et al (2002) Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr Biol 12(16):1419–1423PubMedCrossRefGoogle Scholar
  50. Ingebritsen TS, Parker RA, Gibson DM (1981) Regulation of liver hydroxymethylglutaryl-CoA reductase by a bicyclic phosphorylation system. J Biol Chem 256(3):1138–1144PubMedGoogle Scholar
  51. Inoki K, Zhu T, Guan KL (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115(5):577–590PubMedCrossRefGoogle Scholar
  52. Jager S, Handschin C, St-Pierre J, Spiegelman BM (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 104(29):12017–12022, Pubmed Central PMCID: 1924552PubMedPubMedCentralCrossRefGoogle Scholar
  53. Jakobsen SN, Hardie DG, Morrice N, Tornqvist HE (2001) 5′-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside. J Biol Chem 276(50):46912–46916PubMedCrossRefGoogle Scholar
  54. Jorgensen SB, Viollet B, Andreelli F, Frosig C, Birk JB, Schjerling P et al (2004a) 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 279(2):1070–1079PubMedCrossRefGoogle Scholar
  55. Jorgensen SB, Nielsen JN, Birk JB, Olsen GS, Viollet B, Andreelli F et al (2004b) The alpha2-5′AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading. Diabetes 53(12):3074–3081PubMedCrossRefGoogle Scholar
  56. Jung CH, Ro SH, Cao J, Otto NM, Kim DH (2010) mTOR regulation of autophagy. FEBS Lett 584(7):1287–1295, Pubmed Central PMCID: 2846630PubMedPubMedCentralCrossRefGoogle Scholar
  57. Kane S, Sano H, Liu SC, Asara JM, Lane WS, Garner CC et al (2002) A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain. J Biol Chem 277(25):22115–22118PubMedCrossRefGoogle Scholar
  58. Kim J, Kundu M, Viollet B, Guan KL (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13(2):132–141, Pubmed Central PMCID: 3987946PubMedPubMedCentralCrossRefGoogle Scholar
  59. Kim J, Kim YC, Fang C, Russell RC, Kim JH, Fan W et al (2013) Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell 152(1-2):290–303, Pubmed Central PMCID: 3587159PubMedPubMedCentralCrossRefGoogle Scholar
  60. Kjobsted R, Treebak JT, Fentz J, Lantier L, Viollet B, Birk JB et al (2015) Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner. Diabetes 64(6):2042–2055PubMedCrossRefGoogle Scholar
  61. Koay A, Woodcroft B, Petrie EJ, Yue H, Emanuelle S, Bieri M et al (2010) AMPK beta subunits display isoform specific affinities for carbohydrates. FEBS Lett 584(15):3499–3503PubMedCrossRefGoogle Scholar
  62. Kola B, Farkas I, Christ-Crain M, Wittmann G, Lolli F, Amin F et al (2008) The orexigenic effect of ghrelin is mediated through central activation of the endogenous cannabinoid system. PLoS One 3(3):e1797, Pubmed Central PMCID: 2258435, Epub 2008/03/13. engPubMedPubMedCentralCrossRefGoogle Scholar
  63. Koonen DP, Glatz JF, Bonen A, Luiken JJ (2005) Long-chain fatty acid uptake and FAT/CD36 translocation in heart and skeletal muscle. Biochim Biophys Acta 1736(3):163–180, Epub 2005/10/04. engPubMedCrossRefGoogle Scholar
  64. Kramer HF, Witczak CA, Fujii N, Jessen N, Taylor EB, Arnolds DE et al (2006) Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR, and contraction in mouse skeletal muscle. Diabetes 55(7):2067–2076, Epub 2006/06/29. engPubMedCrossRefGoogle Scholar
  65. Krause U, Bertrand L, Hue L (2002) Control of p70 ribosomal protein S6 kinase and acetyl-CoA carboxylase by AMP-activated protein kinase and protein phosphatases in isolated hepatocytes. Eur J Biochem/FEBS 269(15):3751–3759CrossRefGoogle Scholar
  66. Krawiec BJ, Nystrom GJ, Frost RA, Jefferson LS, Lang CH (2007) AMP-activated protein kinase agonists increase mRNA content of the muscle-specific ubiquitin ligases MAFbx and MuRF1 in C2C12 cells. Am J Physiol Endocrinol Metab 292(6):E1555–E1567PubMedCrossRefGoogle Scholar
  67. Kreuz S, Schoelch C, Thomas L, Rist W, Rippmann JF, Neubauer H (2009) Acetyl-CoA carboxylases 1 and 2 show distinct expression patterns in rats and humans and alterations in obesity and diabetes. Diabetes Metab Res Rev 25(6):577–586PubMedCrossRefGoogle Scholar
  68. Lage R, Dieguez C, Vidal-Puig A, Lopez M (2008) AMPK: a metabolic gauge regulating whole-body energy homeostasis. Trends Mol Med 14(12):539–549PubMedCrossRefGoogle Scholar
  69. Lantier L, Fentz J, Mounier R, Leclerc J, Treebak JT, Pehmoller C et al (2014) AMPK controls exercise endurance, mitochondrial oxidative capacity, and skeletal muscle integrity. FASEB J 28(7):3211–3224PubMedCrossRefGoogle Scholar
  70. Lee WJ, Kim M, Park HS, Kim HS, Jeon MJ, Oh KS et al (2006) AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1. Biochem Biophys Res Commun 340(1):291–295PubMedCrossRefGoogle Scholar
  71. Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM, Kelly DP (2000) Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest 106(7):847–856, Pubmed Central PMCID: 517815PubMedPubMedCentralCrossRefGoogle Scholar
  72. Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B et al (2011) AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab 13(4):376–388, Pubmed Central PMCID: 3086578PubMedPubMedCentralCrossRefGoogle Scholar
  73. Liu Q, Gauthier MS, Sun L, Ruderman N, Lodish H (2010) Activation of AMP-activated protein kinase signaling pathway by adiponectin and insulin in mouse adipocytes: requirement of acyl-CoA synthetases FATP1 and Acsl1 and association with an elevation in AMP/ATP ratio. FASEB J 24(11):4229–4239, Pubmed Central PMCID: 2974418PubMedPubMedCentralCrossRefGoogle Scholar
  74. Luiken JJ, Koonen DP, Willems J, Zorzano A, Becker C, Fischer Y et al (2002) Insulin stimulates long-chain fatty acid utilization by rat cardiac myocytes through cellular redistribution of FAT/CD36. Diabetes 51(10):3113–3119, Epub 2002/09/28. engPubMedCrossRefGoogle Scholar
  75. Luiken JJ, Koonen DP, Coumans WA, Pelsers MM, Binas B, Bonen A et al (2003) Long-chain fatty acid uptake by skeletal muscle is impaired in homozygous, but not heterozygous, heart-type-FABP null mice. Lipids 38(4):491–496, Epub 2003/07/10. engPubMedCrossRefGoogle Scholar
  76. Madsen A, Bozickovic O, Bjune JI, Mellgren G, Sagen JV (2015) Metformin inhibits hepatocellular glucose, lipid and cholesterol biosynthetic pathways by transcriptionally suppressing steroid receptor coactivator 2 (SRC-2). Sci Rep 5:16430, Pubmed Central PMCID: 4637908PubMedPubMedCentralCrossRefGoogle Scholar
  77. Manning BD, Cantley LC (2007) AKT/PKB signaling: navigating downstream. Cell 129(7):1261–1274, Pubmed Central PMCID: 2756685, Epub 2007/07/03. engPubMedPubMedCentralCrossRefGoogle Scholar
  78. Marsin AS, Bertrand L, Rider MH, Deprez J, Beauloye C, Vincent MF et al (2000) Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Curr Biol 10(20):1247–1255PubMedCrossRefGoogle Scholar
  79. Marsin AS, Bouzin C, Bertrand L, Hue L (2002) The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6-phosphofructo-2-kinase. J Biol Chem 277(34):30778–30783, Epub 2002/06/18. engPubMedCrossRefGoogle Scholar
  80. McGee SL, Hargreaves M (2004) Exercise and myocyte enhancer factor 2 regulation in human skeletal muscle. Diabetes 53(5):1208–1214PubMedCrossRefGoogle Scholar
  81. McGee SL, van Denderen BJ, Howlett KF, Mollica J, Schertzer JD, Kemp BE et al (2008) AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5. Diabetes 57(4):860–867PubMedCrossRefGoogle Scholar
  82. Middelbeek RJ, Chambers MA, Tantiwong P, Treebak JT, An D, Hirshman MF et al (2013) Insulin stimulation regulates AS160 and TBC1D1 phosphorylation sites in human skeletal muscle. Nutr Diabetes 3:e74, Pubmed Central PMCID: 3697402, Epub 2013/06/12. engPubMedPubMedCentralCrossRefGoogle Scholar
  83. Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B et al (2004) AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428(6982):569–574PubMedCrossRefGoogle Scholar
  84. Moreno D, Viana R, Sanz P (2009) Two-hybrid analysis identifies PSMD11, a non-ATPase subunit of the proteasome, as a novel interaction partner of AMP-activated protein kinase. Int J Biochem Cell Biol 41(12):2431–2439PubMedCrossRefGoogle Scholar
  85. Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW (2006) Central nervous system control of food intake and body weight. Nature 443(7109):289–295PubMedCrossRefGoogle Scholar
  86. Munday MR, Campbell DG, Carling D, Hardie DG (1988) Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase. Eur J Biochem/FEBS 175(2):331–338CrossRefGoogle Scholar
  87. Muoio DM, Seefeld K, Witters LA, Coleman RA (1999) AMP-activated kinase reciprocally regulates triacylglycerol synthesis and fatty acid oxidation in liver and muscle: evidence that sn-glycerol-3-phosphate acyltransferase is a novel target. Biochem J 338(Pt 3):783–791, Pubmed Central PMCID: 1220117PubMedPubMedCentralCrossRefGoogle Scholar
  88. Nada MA, Abdel-Aleem S, Schulz H (1995) On the rate-limiting step in the beta-oxidation of polyunsaturated fatty acids in the heart. Biochim Biophys Acta 1255(3):244–250, Epub 1995/04/06. engPubMedCrossRefGoogle Scholar
  89. Oligschlaeger Y, Miglianico M, Chanda D, Scholz R, Thali RF, Tuerk R et al (2015) The recruitment of AMP-activated protein kinase to glycogen is regulated by autophosphorylation. J Biol Chem 290(18):11715–11728, Pubmed Central PMCID: 4416872PubMedPubMedCentralCrossRefGoogle Scholar
  90. O’Neill HM, Maarbjerg SJ, Crane JD, Jeppesen J, Jorgensen SB, Schertzer JD et al (2011) 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 USA 108(38):16092–16097, Pubmed Central PMCID: 3179037PubMedPubMedCentralCrossRefGoogle Scholar
  91. Pehmoller C, Treebak JT, Birk JB, Chen S, Mackintosh C, Hardie DG et al (2009) Genetic disruption of AMPK signaling abolishes both contraction- and insulin-stimulated TBC1D1 phosphorylation and 14-3-3 binding in mouse skeletal muscle. Am J Physiol Endocrinol Metab 297(3):E665–E675, Pubmed Central PMCID: 2739697, Epub 2009/06/18. engPubMedPubMedCentralCrossRefGoogle Scholar
  92. Peth A, Nathan JA, Goldberg AL (2013) The ATP costs and time required to degrade ubiquitinated proteins by the 26 S proteasome. J Biol Chem 288(40):29215–29222, Pubmed Central PMCID: 3790020PubMedPubMedCentralCrossRefGoogle Scholar
  93. Polekhina G, Gupta A, Michell BJ, van Denderen B, Murthy S, Feil SC et al (2003) AMPK β subunit targets metabolic stress sensing to glycogen. Curr Biol 13(10):867–871PubMedCrossRefGoogle Scholar
  94. Ronnebaum SM, Patterson C, Schisler JC (2014) Minireview: hey U(PS): metabolic and proteolytic homeostasis linked via AMPK and the ubiquitin proteasome system. Mol Endocrinol 28(10):1602–1615, Pubmed Central PMCID: 4179629PubMedPubMedCentralCrossRefGoogle Scholar
  95. Rose AJ, Jeppesen J, Kiens B, Richter EA (2009) Effects of contraction on localization of GLUT4 and v-SNARE isoforms in rat skeletal muscle. Am J Physiol Regul Integr Comp Physiol 297(5):R1228–R1237, Epub 2009/08/14. engPubMedCrossRefGoogle Scholar
  96. Rowland AF, Fazakerley DJ, James DE (2011) Mapping insulin/GLUT4 circuitry. Traffic 12(6):672–681, Epub 2011/03/16. engPubMedCrossRefGoogle Scholar
  97. Sadler JB, Bryant NJ, Gould GW (2015) Characterization of VAMP isoforms in 3T3-L1 adipocytes: implications for GLUT4 trafficking. Mol Biol Cell 26(3):530–536, Pubmed Central PMCID: 4310743, Epub 2014/12/17. engPubMedPubMedCentralCrossRefGoogle Scholar
  98. Sakamoto K, McCarthy A, Smith D, Green KA, Grahame Hardie D, Ashworth A et al (2005) Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction. EMBO J 24(10):1810–1820, Pubmed Central PMCID: 1142598PubMedPubMedCentralCrossRefGoogle Scholar
  99. Samovski D, Su X, Xu Y, Abumrad NA, Stahl PD (2012) Insulin and AMPK regulate FA translocase/CD36 plasma membrane recruitment in cardiomyocytes via Rab GAP AS160 and Rab8a Rab GTPase. J Lipid Res 53(4):709–717, Pubmed Central PMCID: 3307647PubMedPubMedCentralCrossRefGoogle Scholar
  100. Sano H, Kane S, Sano E, Miinea CP, Asara JM, Lane WS et al (2003) Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation. J Biol Chem 278(17):14599–14602PubMedCrossRefGoogle Scholar
  101. Schwenk RW, Dirkx E, Coumans WA, Bonen A, Klip A, Glatz JF et al (2010) Requirement for distinct vesicle-associated membrane proteins in insulin- and AMP-activated protein kinase (AMPK)-induced translocation of GLUT4 and CD36 in cultured cardiomyocytes. Diabetologia 53(10):2209–2219, Pubmed Central PMCID: 2931635PubMedPubMedCentralCrossRefGoogle Scholar
  102. Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA et al (2005) The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310(5754):1642–1646, Pubmed Central PMCID: 3074427, Epub 2005/11/26. engPubMedPubMedCentralCrossRefGoogle Scholar
  103. Solaz-Fuster MC, Gimeno-Alcaniz JV, Ros S, Fernandez-Sanchez ME, Garcia-Fojeda B, Criado Garcia O et al (2008) Regulation of glycogen synthesis by the laforin-malin complex is modulated by the AMP-activated protein kinase pathway. Hum Mol Genet 17(5):667–678PubMedCrossRefGoogle Scholar
  104. Suwa M, Nakano H, Kumagai S (2003) Effects of chronic AICAR treatment on fiber composition, enzyme activity, UCP3, and PGC-1 in rat muscles. J Appl Physiol 95(3):960–968PubMedCrossRefGoogle Scholar
  105. Takeuchi K, Reue K (2009) Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis. Am J Physiol Endocrinol Metab 296(6):E1195–E1209, Pubmed Central PMCID: 2692402PubMedPubMedCentralCrossRefGoogle Scholar
  106. Tan VP, Miyamoto S (2016) Nutrient-sensing mTORC1: integration of metabolic and autophagic signals. J Mol Cell Cardiol 95:31–41PubMedCrossRefGoogle Scholar
  107. Terada S, Goto M, Kato M, Kawanaka K, Shimokawa T, Tabata I (2002) Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle. Biochem Biophys Res Commun 296(2):350–354PubMedCrossRefGoogle Scholar
  108. Tong JF, Yan X, Zhu MJ, Du M (2009) AMP-activated protein kinase enhances the expression of muscle-specific ubiquitin ligases despite its activation of IGF-1/Akt signaling in C2C12 myotubes. J Cell Biochem 108(2):458–468PubMedCrossRefGoogle Scholar
  109. Vega RB, Huss JM, Kelly DP (2000) The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 20(5):1868–1876, Pubmed Central PMCID: 85369PubMedPubMedCentralCrossRefGoogle Scholar
  110. Wang S, Xu J, Song P, Viollet B, Zou MH (2009) In vivo activation of AMP-activated protein kinase attenuates diabetes-enhanced degradation of GTP cyclohydrolase I. Diabetes 58(8):1893–1901, Pubmed Central PMCID: 2712774PubMedPubMedCentralCrossRefGoogle Scholar
  111. Watanobe H (2002) Leptin directly acts within the hypothalamus to stimulate gonadotropin-releasing hormone secretion in vivo in rats. J Physiol 545(Pt 1):255–268, Pubmed Central PMCID: 2290656PubMedPubMedCentralCrossRefGoogle Scholar
  112. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V et al (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98(1):115–124PubMedCrossRefGoogle Scholar
  113. Wu X, Motoshima H, Mahadev K, Stalker TJ, Scalia R, Goldstein BJ (2003) Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes. Diabetes 52(6):1355–1363PubMedCrossRefGoogle Scholar
  114. Xu J, Wang S, Viollet B, Zou MH (2012) Regulation of the proteasome by AMPK in endothelial cells: the role of O-GlcNAc transferase (OGT). PLoS One 7(5):e36717, Pubmed Central PMCID: 3345026PubMedPubMedCentralCrossRefGoogle Scholar
  115. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S et al (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8(11):1288–1295PubMedCrossRefGoogle Scholar
  116. Yeh LA, Lee KH, Kim KH (1980) Regulation of rat liver acetyl-CoA carboxylase. Regulation of phosphorylation and inactivation of acetyl-CoA carboxylase by the adenylate energy charge. J Biol Chem 255(6):2308–2314PubMedGoogle Scholar
  117. Zarrinpashneh E, Carjaval K, Beauloye C, Ginion A, Mateo P, Pouleur AC et al (2006) Role of the alpha2-isoform of AMP-activated protein kinase in the metabolic response of the heart to no-flow ischemia. Am J Physiol Heart Circ Physiol 291(6):H2875–H2883, Epub 2006/08/01. engPubMedCrossRefGoogle Scholar
  118. Zerial M, McBride H (2001) Rab proteins as membrane organizers. Nat Rev Mol Cell Biol 2(2):107–117PubMedCrossRefGoogle Scholar
  119. Zhang YL, Guo H, Zhang CS, Lin SY, Yin Z, Peng Y et al (2013) AMP as a low-energy charge signal autonomously initiates assembly of AXIN-AMPK-LKB1 complex for AMPK activation. Cell Metab 18(4):546–555PubMedCrossRefGoogle Scholar
  120. Zhang CS, Jiang B, Li M, Zhu M, Peng Y, Zhang YL et al (2014) The lysosomal v-ATPase-Ragulator complex is a common activator for AMPK and mTORC1, acting as a switch between catabolism and anabolism. Cell Metab 20(3):526–540PubMedCrossRefGoogle Scholar
  121. Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ et al (2002) AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci USA 99(25):15983–15987, Pubmed Central PMCID: 138551PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Yeliz Angin
    • 1
  • Christophe Beauloye
    • 1
    • 2
  • Sandrine Horman
    • 1
  • Luc Bertrand
    • 1
  1. 1.Pole of Cardiovascular ResearchUniversité catholique de Louvain, Institut de Recherche Expérimentale et CliniqueBrusselsBelgium
  2. 2.Division of CardiologyCliniques universitaires Saint-LucBrusselsBelgium

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