1932

Abstract

The adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway arose early during evolution of eukaryotic cells, when it appears to have been involved in the response to glucose starvation and perhaps also in monitoring the output of the newly acquired mitochondria. Due to the advent of hormonal regulation of glucose homeostasis, glucose starvation is a less frequent event for mammalian cells than for single-celled eukaryotes. Nevertheless, the AMPK system has been preserved in mammals where, by monitoring cellular AMP:adenosine triphosphate (ATP) and adenosine diphosphate (ADP):ATP ratios and balancing the rates of catabolism and ATP consumption, it maintains energy homeostasis at a cell-autonomous level. In addition, hormones involved in maintaining energy balance at the whole-body level interact with AMPK in the hypothalamus. AMPK is activated by two widely used clinical drugs, metformin and aspirin, and also by many natural products of plants that are either derived from traditional medicines or are promoted as “nutraceuticals.”

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2014-07-17
2024-04-25
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Literature Cited

  1. Akman HO, Sampayo JN, Ross FA, Scott JW, Wilson G. 1.  et al. 2007. Fatal infantile cardiac glycogenosis with phosphorylase kinase deficiency and a mutation in the gamma-2 subunit of AMP-activated protein kinase. Pediatr. Res. 62:499–504 [Google Scholar]
  2. Amodeo GA, Rudolph MJ, Tong L. 2.  2007. Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1. Nature 449:492–95 [Google Scholar]
  3. Anderson KA, Ribar TJ, Lin F, Noeldner PK, Green MF. 3.  et al. 2008. Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab. 7:377–88 [Google Scholar]
  4. Apfeld J, O'Connor G, McDonagh T, Distefano PS, Curtis R. 4.  2004. The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev. 18:3004–9 [Google Scholar]
  5. Banerjee S, Ghoshal S, Porter TD. 5.  2012. Phosphorylation of hepatic AMP-activated protein kinase and liver kinase B1 is increased after a single oral dose of green tea extract to mice. Nutr. Res. 32:985–90 [Google Scholar]
  6. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C. 6.  et al. 2006. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–42 [Google Scholar]
  7. Beg ZH, Allmann DW, Gibson DM. 7.  1973. Modulation of 3-hydroxy-3-methylglutaryl coenzyme: a reductase activity with cAMP and with protein fractions of rat liver cytosol. Biochem. Biophys. Res. Comm. 54:1362–69 [Google Scholar]
  8. Braidot E, Zancani M, Petrussa E, Peresson C, Bertolini A. 8.  et al. 2008. Transport and accumulation of flavonoids in grapevine (Vitis vinifera L.). Plant Signal. Behav. 3:626–32 [Google Scholar]
  9. Browne GJ, Finn SG, Proud CG. 9.  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. 279:12220–31 [Google Scholar]
  10. Brunmair B, Staniek K, Gras F, Scharf N, Althaym A. 10.  et al. 2004. Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions?. Diabetes 53:1052–59 [Google Scholar]
  11. Bultot L, Guigas B, Von Wilamowitz-Moellendorff A, Maisin L, Vertommen D. 11.  et al. 2012. AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase. Biochem. J. 443:193–203 [Google Scholar]
  12. Burwinkel B, Scott JW, Buhrer C, van Landeghem FK, Cox GF. 12.  et al. 2005. Fatal congenital heart glycogenosis caused by a recurrent activating R531Q mutation in the g2 subunit of AMP-activated protein kinase (PRKAG2), not by phosphorylase kinase deficiency. Am. J. Hum. Genet. 76:1034–49 [Google Scholar]
  13. Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L. 13.  et al. 2009. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 458:1056–60 [Google Scholar]
  14. Carling D, Mayer FV, Sanders MJ, Gamblin SJ. 14.  2011. AMP-activated protein kinase: nature's energy sensor. Nat. Chem. Biol. 7:512–18 [Google Scholar]
  15. Carling D, Zammit VA, Hardie DG. 15.  1987. A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett. 223:217–22 [Google Scholar]
  16. Carlson CA, Kim KH. 16.  1973. Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. J. Biol. Chem. 248:378–80 [Google Scholar]
  17. Chen D, Pamu S, Cui Q, Chan TH, Dou QP. 17.  2012. Novel epigallocatechin gallate (EGCG) analogs activate AMP-activated protein kinase pathway and target cancer stem cells. Bioorg. Med. Chem. 20:3031–37 [Google Scholar]
  18. Chen L, Wang J, Zhang YY, Yan SF, Neumann D. 18.  et al. 2012. AMP-activated protein kinase undergoes nucleotide-dependent conformational changes. Nat. Struct. Mol. Biol. 19:716–18 [Google Scholar]
  19. Chen XB, Zhuang JJ, Liu JH, Lei M, Ma L. 19.  et al. 2011. Potential AMPK activators of cucurbitane triterpenoids from Siraitia grosvenorii Swingle. Bioorg. Med. Chem. 19:5776–81 [Google Scholar]
  20. Chen YY, Lee MH, Hsu CC, Wei CL, Tsai YC. 20.  2012. Methyl cinnamate inhibits adipocyte differentiation via activation of the CaMKK2-AMPK pathway in 3T3-L1 preadipocytes. J. Agric. Food Chem. 60:955–63 [Google Scholar]
  21. Chen Z, Zhang L, Yi J, Yang Z, Zhang Z, Li Z. 21.  2012. Promotion of adiponectin multimerization by emodin, a novel AMPK activator with PPARγ activity. J. Cell. Biochem. 113:3547–58 [Google Scholar]
  22. Claret M, Smith MA, Batterham RL, Selman C, Choudhury AI. 22.  et al. 2007. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J. Clin. Invest. 117:2325–36 [Google Scholar]
  23. Corton JM, Gillespie JG, Hawley SA, Hardie DG. 23.  1995. 5-Aminoimidazole-4-carboxamide ribonucleoside: a specific method for activating AMP-activated protein kinase in intact cells?. Eur. J. Biochem. 229:558–65 [Google Scholar]
  24. Coven DL, Hu X, Cong L, Bergeron R, Shulman GI. 24.  et al. 2003. Physiologic role of AMP-activated protein kinase (AMPK) in the heart: graded activation during exercise. Am. J. Physiol. 285:E629–36 [Google Scholar]
  25. Cronstein BN, Montesinos MC, Weissmann G. 25.  1999. Salicylates and sulfasalazine, but not glucocorticoids, inhibit leukocyte accumulation by an adenosine-dependent mechanism that is independent of inhibition of prostaglandin synthesis and p105 of NFκB. Proc. Natl. Acad. Sci. USA 96:6377–81 [Google Scholar]
  26. Dagon Y, Hur E, Zheng B, Wellenstein K, Cantley LC, Kahn BB. 26.  2012. p70S6 Kinase phosphorylates AMPK on serine 491 to mediate leptin's effect on food intake. Cell Metab. 16:104–12 [Google Scholar]
  27. Daval M, Diot-Dupuy F, Bazin R, Hainault I, Viollet B. 27.  et al. 2005. Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes. J. Biol. Chem. 280:25250–57 [Google Scholar]
  28. Davies SP, Hawley SA, Woods A, Carling D, Haystead TAJ, Hardie DG. 28.  1994. Purification of the AMP-activated protein kinase on ATP-γ-Sepharose and analysis of its subunit structure. Eur. J. Biochem. 223:351–57 [Google Scholar]
  29. Davies SP, Helps NR, Cohen PTW, Hardie DG. 29.  1995. 5′-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2Cα and native bovine protein phosphatase-2AC. FEBS Lett. 377:421–25 [Google Scholar]
  30. Davies SP, Sim AT, Hardie DG. 30.  1990. Location and function of three sites phosphorylated on rat acetyl-CoA carboxylase by the AMP-activated protein kinase. Eur. J. Biochem. 187:183–90 [Google Scholar]
  31. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA. 31.  et al. 2011. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331:456–61 [Google Scholar]
  32. El-Mir MY, Nogueira V, Fontaine E, Averet N, Rigoulet M, Leverve X. 32.  2000. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J. Biol. Chem. 275:223–28 [Google Scholar]
  33. Erion DM, Shulman GI. 33.  2010. Diacylglycerol-mediated insulin resistance. Nat. Med. 16:400–2 [Google Scholar]
  34. Fogarty S, Hawley SA, Green KA, Saner N, Mustard KJ, Hardie DG. 34.  2010. Calmodulin-dependent protein kinase kinase-β activates AMPK without forming a stable complex: synergistic effects of Ca2+ and AMP. Biochem. J. 426:109–18 [Google Scholar]
  35. Foretz M, Hebrard S, Leclerc J, Zarrinpashneh E, Soty M. 35.  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. 120:2355–69 [Google Scholar]
  36. Friedman JM, Halaas JL. 36.  1998. Leptin and the regulation of body weight in mammals. Nature 395:763–70 [Google Scholar]
  37. Fryer LG, Foufelle F, Barnes K, Baldwin SA, Woods A, Carling D. 37.  2002. Characterization of the role of the AMP-activated protein kinase in the stimulation of glucose transport in skeletal muscle cells. Biochem. J. 363:167–74 [Google Scholar]
  38. Fullerton MD, Galic S, Marcinko K, Sikkema S, Pulinilkunnil T. 38.  et al. 2013. Single phosphorylation sites in ACC1 and ACC2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat. Med. 19:1649–54 [Google Scholar]
  39. Garton AJ, Campbell DG, Carling D, Hardie DG, Colbran RJ, Yeaman SJ. 39.  1989. Phosphorylation of bovine hormone-sensitive lipase by the AMP-activated protein kinase. A possible antilipolytic mechanism. Eur. J. Biochem. 179:249–54 [Google Scholar]
  40. Gillespie JG, Hardie DG. 40.  1992. Phosphorylation and inactivation of HMG-CoA reductase at the AMP-activated protein kinase site in response to fructose treatment of isolated rat hepatocytes. FEBS Lett. 306:59–62 [Google Scholar]
  41. Goto T, Teraminami A, Lee JY, Ohyama K, Funakoshi K. 41.  et al. 2012. Tiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic mice. J. Nutr. Biochem. 23:768–76 [Google Scholar]
  42. Gowans GJ, Hawley SA, Ross FA, Hardie DG. 42.  2013. AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab. 18:556–66 [Google Scholar]
  43. Greer EL, Brunet A. 43.  2009. Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans. Aging Cell 8:113–27 [Google Scholar]
  44. Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A. 44.  et al. 2008. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol. Cell 30:214–26 [Google Scholar]
  45. Habets DD, Coumans WA, El Hasnaoui M, Zarrinpashneh E, Bertrand L. 45.  et al. 2009. Crucial role for LKB1 to AMPKα2 axis in the regulation of CD36-mediated long-chain fatty acid uptake into cardiomyocytes. Biochim. Biophys. Acta 1791:212–19 [Google Scholar]
  46. Hardie DG. 46.  2013. AMPK: a target for drugs and natural products with effects on both diabetes and cancer. Diabetes 62:2164–72 [Google Scholar]
  47. Hardie DG, Carling D, Carlson M. 47.  1998. The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell?. Annu. Rev. Biochem. 67:821–55 [Google Scholar]
  48. Hardie DG, Hawley SA. 48.  2001. AMP-activated protein kinase: the energy charge hypothesis revisited. BioEssays 23:1112–19 [Google Scholar]
  49. Haurie V, Boucherie H, Sagliocco F. 49.  2003. The Snf1 protein kinase controls the induction of genes of the iron uptake pathway at the diauxic shift in Saccharomyces cerevisiae. J. Biol. Chem. 278:45391–96 [Google Scholar]
  50. Hawley SA, Boudeau J, Reid JL, Mustard KJ, Udd L. 50.  et al. 2003. Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade. J. Biol. 2:28 [Google Scholar]
  51. Hawley SA, Davison M, Woods A, Davies SP, Beri RK. 51.  et al. 1996. Characterization of the AMP-activated protein kinase kinase from rat liver, and identification of threonine-172 as the major site at which it phosphorylates and activates AMP-activated protein kinase. J. Biol. Chem. 271:27879–87 [Google Scholar]
  52. Hawley SA, Fullerton MD, Ross FA, Schertzer JD, Chevtzoff C. 52.  et al. 2012. The ancient drug salicylate directly activates AMP-activated protein kinase. Science 336:918–22 [Google Scholar]
  53. Hawley SA, Pan DA, Mustard KJ, Ross L, Bain J. 53.  et al. 2005. Calmodulin-dependent protein kinase kinase-β is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab. 2:9–19 [Google Scholar]
  54. Hawley SA, Ross FA, Chevtzoff C, Green KA, Evans A. 54.  et al. 2010. Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab. 11:554–65 [Google Scholar]
  55. Hawley SA, Ross FA, Gowans GJ, Tibarewal P, Leslie NR, Hardie DG. 55.  2014. Phosphorylation by Akt within the ST loop of AMPK-α1 down-regulates its activation in tumour cells. J. 459275–87
  56. Higgs GA, Salmon JA, Henderson B, Vane JR. 56.  1987. Pharmacokinetics of aspirin and salicylate in relation to inhibition of arachidonate cyclooxygenase and antiinflammatory activity. Proc. Natl. Acad. Sci. USA 84:1417–20 [Google Scholar]
  57. Holmes BF, Kurth-Kraczek EJ, Winder WW. 57.  1999. Chronic activation of 5′-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle. J. Appl. Physiol. 87:1990–95 [Google Scholar]
  58. Hoppe S, Bierhoff H, Cado I, Weber A, Tiebe M. 58.  et al. 2009. AMP-activated protein kinase adapts rRNA synthesis to cellular energy supply. Proc. Natl. Acad. Sci. USA 106:17781–86 [Google Scholar]
  59. Horman S, Vertommen D, Heath R, Neumann D, Mouton V. 59.  et al. 2006. Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinase α-subunits in heart via hierarchical phosphorylation of Ser485/491. J. Biol. Chem. 281:5335–40 [Google Scholar]
  60. Huang HC, Lin JK. 60.  2011. Pu-erh tea, green tea, and black tea suppresses hyperlipidemia, hyperleptinemia and fatty acid synthase through activating AMPK in rats fed a high-fructose diet. Food Funct. 3:170–77 [Google Scholar]
  61. 61.  Deleted in proof
  62. Huang SL, Yu RT, Gong J, Feng Y, Dai YL. 62.  et al. 2012. Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice. Diabetologia 55:1469–81 [Google Scholar]
  63. Hurley RL, Anderson KA, Franzone JM, Kemp BE, Means AR, Witters LA. 63.  2005. The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J. Biol. Chem. 280:29060–66 [Google Scholar]
  64. Hwang SL, Yang JH, Jeong YT, Kim YD, Li X. 64.  et al. 2013. Tanshinone IIA improves endoplasmic reticulum stress-induced insulin resistance through AMP-activated protein kinase. Biochem. Biophys. Res. Comm. 430:1246–52 [Google Scholar]
  65. Hwang YP, Choi JH, Han EH, Kim HG, Wee JH. 65.  et al. 2011. Purple sweet potato anthocyanins attenuate hepatic lipid accumulation through activating adenosine monophosphate-activated protein kinase in human HepG2 cells and obese mice. Nutr. Res. 31:896–906 [Google Scholar]
  66. Ingebritsen TS, Lee H, Parker RA, Gibson DM. 66.  1978. Reversible modulation of the activities of both liver microsomal hydroxymethylglutaryl coenzyme A reductase and its inactivating enzyme. Evidence for regulation by phosphorylation-dephosphorylation. Biochem. Biophys. Res. Comm. 81:1268–77 [Google Scholar]
  67. Inoki K, Zhu T, Guan KL. 67.  2003. TSC2 mediates cellular energy response to control cell growth and survival. Cell 115:577–90 [Google Scholar]
  68. Jager S, Handschin C, St-Pierre J, Spiegelman BM. 68.  2007. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α. Proc. Natl. Acad. Sci. USA 104:12017–22 [Google Scholar]
  69. Jaiswal N, Yadav PP, Maurya R, Srivastava AK, Tamrakar AK. 69.  2011. Karanjin from Pongamia pinnata induces GLUT4 translocation in skeletal muscle cells in a phosphatidylinositol-3-kinase-independent manner. Eur. J. Pharmacol. 670:22–8 [Google Scholar]
  70. Jeong GS, Lee DS, Li B, Kim JJ, Kim EC, Kim YC. 70.  2011. Anti-inflammatory effects of lindenenyl acetate via heme oxygenase-1 and AMPK in human periodontal ligament cells. Eur. J. Pharmacol. 670:295–303 [Google Scholar]
  71. Jeong HW, Hsu KC, Lee JW, Ham M, Huh JY. 71.  et al. 2009. Berberine suppresses proinflammatory responses through AMPK activation in macrophages. Am. J. Physiol. Endocrinol. Metab. 296:E955–64 [Google Scholar]
  72. Jeong YT, Song CH. 72.  2011. Antidiabetic activities of extract from Malva verticillata seed via the activation of AMP-activated protein kinase. J. Microbiol. Biotechnol. 21:921–29 [Google Scholar]
  73. Jorgensen SB, Nielsen JN, Birk JB, Olsen GS, Viollet B. 73.  et al. 2004. The α2-5′AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading. Diabetes 53:3074–81 [Google Scholar]
  74. Jorgensen SB, Viollet B, Andreelli F, Frosig C, Birk JB. 74.  et al. 2004. Knockout of the α2 but not α1 5′-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside but not contraction-induced glucose uptake in skeletal muscle. J. Biol. Chem. 279:1070–79 [Google Scholar]
  75. Kadowaki T, Yamauchi T. 75.  2005. Adiponectin and adiponectin receptors. Endocr. Rev. 26:439–51 [Google Scholar]
  76. Kapoor S. 76.  2012. Attenuation of tumor growth by honokiol: an evolving role in oncology. Drug Discov. Ther. 6:327–28 [Google Scholar]
  77. Katinka MD, Duprat S, Cornillot E, Metenier G, Thomarat F. 77.  et al. 2001. Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 414:450–53 [Google Scholar]
  78. Kelley DE, Goodpaster BH, Storlien L. 78.  2002. Muscle triglyceride and insulin resistance. Annu. Rev. Nutr. 22:325–46 [Google Scholar]
  79. Khanal P, Kang BS, Yun HJ, Cho HG, Makarieva TN, Choi HS. 79.  2011. Aglycon of rhizochalin from the Rhizochalina incrustata induces apoptosis via activation of AMP-activated protein kinase in HT-29 colon cancer cells. Biol. Pharm. Bull. 34:1553–58 [Google Scholar]
  80. Kim DY, Kim MS, Sa BK, Kim MB, Hwang JK. 80.  2012. Boesenbergia pandurata attenuates diet-induced obesity by activating AMP-activated protein kinase and regulating lipid metabolism. Int. J. Mol. Sci. 13:994–1005 [Google Scholar]
  81. Kim DY, Park YG, Quan HY, Kim SJ, Jung MS, Chung SH. 81.  2012. Ginsenoside Rd stimulates the differentiation and mineralization of osteoblastic MC3T3-E1 cells by activating AMP-activated protein kinase via the BMP-2 signaling pathway. Fitoterapia 83:215–22 [Google Scholar]
  82. Kim J, Kim YC, Fang C, Russell RC, Kim JH. 82.  et al. 2013. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell 152:290–303 [Google Scholar]
  83. Kim J, Kundu M, Viollet B, Guan KL. 83.  2011. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol. 13:132–41 [Google Scholar]
  84. Kim JH, Lee JO, Lee SK, Kim N, You GY. 84.  et al. 2013. Celastrol suppresses breast cancer MCF-7 cell viability via the AMP-activated protein kinase (AMPK)-induced p53-polo like kinase 2 (PLK-2) pathway. Cell. Signal. 25:805–13 [Google Scholar]
  85. Kim MS, Hur HJ, Kwon DY, Hwang JT. 85.  2012. Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese mice. Mol. Cell. Endocrinol. 358:127–34 [Google Scholar]
  86. Kim SH, Park EJ, Lee CR, Chun JN, Cho NH. 86.  et al. 2012. Geraniol induces cooperative interaction of apoptosis and autophagy to elicit cell death in PC-3 prostate cancer cells. Int. J. Oncol. 40:1683–90 [Google Scholar]
  87. Koo SH, Flechner L, Qi L, Zhang X, Screaton RA. 87.  et al. 2005. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 437:1109–14 [Google Scholar]
  88. Krawczyk CM, Holowka T, Sun J, Blagih J, Amiel E. 88.  et al. 2010. Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood 115:4742–49 [Google Scholar]
  89. Kubota N, Yano W, Kubota T, Yamauchi T, Itoh S. 89.  et al. 2007. Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake. Cell Metab. 6:55–68 [Google Scholar]
  90. Kudo N, Barr AJ, Barr RL, Desai S, Lopaschuk GD. 90.  1995. High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5′-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. J. Biol. Chem. 270:17513–20 [Google Scholar]
  91. Kurth-Kraczek EJ, Hirshman MF, Goodyear LJ, Winder WW. 91.  1999. 5′-AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes 48:1667–71 [Google Scholar]
  92. Ladurner A, Atanasov AG, Heiss EH, Baumgartner L, Schwaiger S. 92.  et al. 2012. 2-(2,4-dihydroxyphenyl)-5-(E)-propenylbenzofuran promotes endothelial nitric oxide synthase activity in human endothelial cells. Biochem. Pharmacol. 84:804–12 [Google Scholar]
  93. Lai CS, Tsai ML, Badmaev V, Jimenez M, Ho CT, Pan MH. 93.  2012. Xanthigen suppresses preadipocyte differentiation and adipogenesis through down-regulation of PPARγ and C/EBPs and modulation of SIRT-1, AMPK, and FoxO pathways. J. Agric. Food Chem. 60:1094–101 [Google Scholar]
  94. Lee JW, Choe SS, Jang H, Kim J, Jeong HW. 94.  et al. 2012. AMPK activation with glabridin ameliorates adiposity and lipid dysregulation in obesity. J. Lipid Res. 53:1277–86 [Google Scholar]
  95. Lee NY, Park KY, Min HJ, Song KY, Lim YY. 95.  et al. 2012. Inhibitory effect of vitamin U (S-methylmethionine sulfonium chloride) on differentiation in 3T3-L1 pre-adipocyte cell lines. Ann. Dermatol. 24:39–44 [Google Scholar]
  96. Lee SH, Kang SM, Ko SC, Lee DH, Jeon YJ. 96.  2012. Octaphlorethol A, a novel phenolic compound isolated from a brown alga, Ishige foliacea, increases glucose transporter 4-mediated glucose uptake in skeletal muscle cells. Biochem. Biophys. Res. Commun. 420:576–81 [Google Scholar]
  97. Lee WH, Lin RJ, Lin SY, Chen YC, Lin HM, Liang YC. 97.  2011. Osthole enhances glucose uptake through activation of AMP-activated protein kinase in skeletal muscle cells. J. Agric. Food Chem. 59:12874–81 [Google Scholar]
  98. Lee YS, Cha BY, Choi SS, Harada Y, Choi BK. 98.  et al. 2012. Fargesin improves lipid and glucose metabolism in 3T3-L1 adipocytes and high-fat diet-induced obese mice. Biofactors 38:300–8 [Google Scholar]
  99. Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ. 99.  et al. 2006. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes 55:2256–64 [Google Scholar]
  100. Li Y, Xu S, Mihaylova MM, Zheng B, Hou X. 100.  et al. 2011. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 13:376–88 [Google Scholar]
  101. Liao CC, Ou TT, Huang HP, Wang CJ. 101.  2013. The inhibition of oleic acid induced hepatic lipogenesis and the promotion of lipolysis by caffeic acid via up-regulation of AMPK. J. Sci. Food Agric. 94:1154–62 [Google Scholar]
  102. Lin VC, Tsai YC, Lin JN, Fan LL, Pan MH. 102.  et al. 2012. Activation of AMPK by pterostilbene suppresses lipogenesis and cell-cycle progression in p53 positive and negative human prostate cancer cells. J. Agric. Food Chem. 60:6399–407 [Google Scholar]
  103. Lin YC, Hung CM, Tsai JC, Lee JC, Chen YL. 103.  et al. 2010. Hispidulin potently inhibits human glioblastoma multiforme cells through activation of AMP-activated protein kinase (AMPK). J. Agric. Food Chem. 58:9511–17 [Google Scholar]
  104. Liu Z, Li X, Simoneau AR, Jafari M, Zi X. 104.  2012. Rhodiola rosea extracts and salidroside decrease the growth of bladder cancer cell lines via inhibition of the mTOR pathway and induction of autophagy. Mol. Carcinog. 51:257–67 [Google Scholar]
  105. Lopez M, Varela L, Vazquez MJ, Rodriguez-Cuenca S, Gonzalez CR. 105.  et al. 2010. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat. Med. 16:1001–8 [Google Scholar]
  106. Luquet S, Phillips CT, Palmiter RD. 106.  2007. NPY/AgRP neurons are not essential for feeding responses to glucoprivation. Peptides 28:214–25 [Google Scholar]
  107. Maclagan TJ. 107.  1876. The treatment of acute rheumatism by salicin. Lancet 113:875–77 [Google Scholar]
  108. Marsin AS, Bertrand L, Rider MH, Deprez J, Beauloye C. 108.  et al. 2000. Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Curr. Biol. 10:1247–55 [Google Scholar]
  109. Marsin AS, Bouzin C, Bertrand L, Hue L. 109.  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. 277:30778–83 [Google Scholar]
  110. Mayer FV, Heath R, Underwood E, Sanders MJ, Carmena D. 110.  et al. 2011. ADP regulates SNF1, the Saccharomyces cerevisiae homolog of AMP-activated protein kinase. Cell Metab. 14:707–14 [Google Scholar]
  111. McCrimmon RJ, Shaw M, Fan X, Cheng H, Ding Y. 111.  et al. 2008. Key role for AMP-activated protein kinase in the ventromedial hypothalamus in regulating counterregulatory hormone responses to acute hypoglycemia. Diabetes 57:444–50 [Google Scholar]
  112. McGee SL, van Denderen BJ, Howlett KF, Mollica J, Schertzer JD. 112.  et al. 2008. AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5. Diabetes 57:860–67 [Google Scholar]
  113. Merrill GM, Kurth E, Hardie DG, Winder WW. 113.  1997. AICAR decreases malonyl-CoA and increases fatty acid oxidation in skeletal muscle of the rat. Am. J. Physiol. 273:E1107–12 [Google Scholar]
  114. Mihaylova MM, Vasquez DS, Ravnskjaer K, Denechaud PD, Yu RT. 114.  et al. 2011. Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis. Cell 145:607–21 [Google Scholar]
  115. Miller RA, Chu Q, Xie J, Foretz M, Viollet B, Birnbaum MJ. 115.  2013. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature 494:256–60 [Google Scholar]
  116. Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A. 116.  et al. 2004. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428:569–74 [Google Scholar]
  117. Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C. 117.  et al. 2002. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415:339–43 [Google Scholar]
  118. Miranda-Saavedra D, Stark MJ, Packer JC, Vivares CP, Doerig C, Barton GJ. 118.  2007. The complement of protein kinases of the microsporidium Encephalitozoon cuniculi in relation to those of Saccharomyces cerevisiae and Schizosaccharomyces pombe. BMC Genomics 8:309 [Google Scholar]
  119. Mitchelhill KI, Stapleton D, Gao G, House C, Michell B. 119.  et al. 1994. Mammalian AMP-activated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase. J. Biol. Chem. 269:2361–64 [Google Scholar]
  120. Mooney MH, Fogarty S, Stevenson C, Gallagher AM, Palit P. 120.  et al. 2008. Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice. Br. J. Pharmacol. 153:1669–77 [Google Scholar]
  121. Mu J, Brozinick JT, Valladares O, Bucan M, Birnbaum MJ. 121.  2001. A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle. Mol. Cell 7:1085–94 [Google Scholar]
  122. Munday MR, Campbell DG, Carling D, Hardie DG. 122.  1988. Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase. Eur. J. Biochem. 175:331–38 [Google Scholar]
  123. Muoio DM, Seefeld K, Witters LA, Coleman RA. 123.  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. 338:783–91 [Google Scholar]
  124. Narkar VA, Downes M, Yu RT, Embler E, Wang YX. 124.  et al. 2008. AMPK and PPARδ agonists are exercise mimetics. Cell 134:405–15 [Google Scholar]
  125. Niu Y, Li S, Na L, Feng R, Liu L. 125.  et al. 2012. Mangiferin decreases plasma free fatty acids through promoting its catabolism in liver by activation of AMPK. PLoS ONE 7:e30782 [Google Scholar]
  126. O'Neill HM, Maarbjerg SJ, Crane JD, Jeppesen J, Jorgensen SB. 126.  et al. 2011. AMP-activated protein kinase (AMPK) β1β2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. Proc. Natl. Acad. Sci. USA 108:16092–97 [Google Scholar]
  127. O'Neill LA, Hardie DG. 127.  2013. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493:346–55 [Google Scholar]
  128. Oakhill JS, Scott JW, Kemp BE. 128.  2012. AMPK functions as an adenylate charge-regulated protein kinase. Trends Endocrinol. Metab. 23:125–32 [Google Scholar]
  129. Oakhill JS, Steel R, Chen ZP, Scott JW, Ling N. 129.  et al. 2011. AMPK is a direct adenylate charge-regulated protein kinase. Science 332:1433–35 [Google Scholar]
  130. Ono M, Fujimori K. 130.  2011. Antiadipogenic effect of dietary apigenin through activation of AMPK in 3T3-L1 cells. J. Agric. Food Chem. 59:13346–52 [Google Scholar]
  131. Owen MR, Doran E, Halestrap AP. 131.  2000. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem. J. 348:607–14 [Google Scholar]
  132. Pan CH, Tsai CH, Lin WH, Chen GY, Wu CH. 132.  2012. Ethanolic extract of Vitis thunbergii exhibits lipid lowering properties via modulation of the AMPK-ACC pathway in hypercholesterolemic rabbits. Evid. Based Complement. Alternat. Med. 2012:436786 [Google Scholar]
  133. Pehmoller C, Treebak JT, Birk JB, Chen S, Mackintosh C. 133.  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:E665–75 [Google Scholar]
  134. Polakiewicz RD, Schieferl SM, Gingras AC, Sonenberg N, Comb MJ. 134.  1998. μ-Opioid receptor activates signaling pathways implicated in cell survival and translational control. J. Biol. Chem. 273:23534–41 [Google Scholar]
  135. Preston SJ, Arnold MH, Beller EM, Brooks PM, Buchanan WW. 135.  1989. Comparative analgesic and anti-inflammatory properties of sodium salicylate and acetylsalicylic acid (aspirin) in rheumatoid arthritis. Br. J. Clin. Pharmacol. 27:607–11 [Google Scholar]
  136. Ptitsyn LR, Nomura K, Sklyar IV, Ravcheeva AB. 136.  2011. The 1,4-naphthoquinone derivative from Pyrola rotundifolia activates AMPK phosphorylation in C2C12 myotubes. Fitoterapia 82:1285–89 [Google Scholar]
  137. Pu P, Gao DM, Mohamed S, Chen J, Zhang J. 137.  et al. 2012. Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet. Arch. Biochem. Biophys. 518:61–70 [Google Scholar]
  138. Qian Q, Liu X, He W, An Y, Chen Q. 138.  et al. 2012. TG accumulation inhibitory effects of Jinqi formula by AMPK signaling pathway. J. Ethnopharmacol. 143:41–48 [Google Scholar]
  139. Quan HY, Yuan HD, Jung MS, Ko SK, Park YG, Chung SH. 139.  2011. Ginsenoside Re lowers blood glucose and lipid levels via activation mice. Int. J. Mol. Med. 29:73–80 [Google Scholar]
  140. Romero-Perez AI, Lamuela-Raventos RM, Andres-Lacueva C, de La Torre-Boronat MC. 140.  2001. Method for the quantitative extraction of resveratrol and piceid isomers in grape berry skins. Effect of powdery mildew on the stilbene content. J. Agric. Food Chem. 49:210–15 [Google Scholar]
  141. Roth GJ, Stanford N, Majerus PW. 141.  1975. Acetylation of prostaglandin synthase by aspirin. Proc. Natl. Acad. Sci. USA 72:3073–76 [Google Scholar]
  142. Russell RC, Tian Y, Yuan H, Park HW, Chang YY. 142.  et al. 2013. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat. Cell Biol. 15:741–50 [Google Scholar]
  143. Rutter GA, Leclerc I. 143.  2009. The AMP-regulated kinase family: enigmatic targets for diabetes therapy. Mol. Cell. Endocrinol. 297:41–49 [Google Scholar]
  144. Sag D, Carling D, Stout RD, Suttles J. 144.  2008. Adenosine 5′-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype. J. Immunol. 181:8633–41 [Google Scholar]
  145. Sakamoto K, Goransson O, Hardie DG, Alessi DR. 145.  2004. Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR. Am. J. Physiol. Endocrinol. Metab. 287:E310–17 [Google Scholar]
  146. Sakamoto K, McCarthy A, Smith D, Green KA, Hardie DG. 146.  et al. 2005. Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction. EMBO J. 24:1810–20 [Google Scholar]
  147. Salt IP, Johnson G, Ashcroft SJH, Hardie DG. 147.  1998. AMP-activated protein kinase is activated by low glucose in cell lines derived from pancreatic β cells, and may regulate insulin release. Biochem. J. 335:533–39 [Google Scholar]
  148. Scott JW, Hawley SA, Green KA, Anis M, Stewart G. 148.  et al. 2004. CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. J. Clin. Invest. 113:274–84 [Google Scholar]
  149. Seo JB, Park SW, Choe SS, Jeong HW, Park JY. 149.  et al. 2012. Foenumoside B from Lysimachia foenum-graecum inhibits adipocyte differentiation and obesity induced by high-fat diet. Biochem. Biophys. Res. Comm. 417:800–6 [Google Scholar]
  150. Shao JJ, Zhang AP, Qin W, Zheng L, Zhu YF, Chen X. 150.  2012. AMP-activated protein kinase (AMPK) activation is involved in chrysin-induced growth inhibition and apoptosis in cultured A549 lung cancer cells. Biochem. Biophys. Res. Comm. 423:448–53 [Google Scholar]
  151. Shin SS, Park D, Lee HY, Hong Y, Choi J. 151.  et al. 2012. The herbal composition GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra sinica reduces obesity via skeletal muscle AMPK and PPARα. Pharmaceut. Biol. 50:506–15 [Google Scholar]
  152. Shitan N, Yazaki K. 152.  2007. Accumulation and membrane transport of plant alkaloids. Curr. Pharm. Biotechnol. 8:244–52 [Google Scholar]
  153. Son MJ, Minakawa M, Miura Y, Yagasaki K. 153.  2013. Aspalathin improves hyperglycemia and glucose intolerance in obese diabetic ob/ob mice. Eur. J. Nutr. 52:1607–19 [Google Scholar]
  154. Song KH, Lee SH, Kim BY, Park AY, Kim JY. 154.  2013. Extracts of Scutellaria baicalensis reduced body weight and blood triglyceride in db/db mice. Phytother. Res. 27:244–50 [Google Scholar]
  155. Steinberg GR, Dandapani M, Hardie DG. 155.  2013. AMPK: mediating the metabolic effects of salicylate-based drugs?. Trends Endocrinol. Metab. 24:481–87 [Google Scholar]
  156. Tang X, Zhuang J, Chen J, Yu L, Hu L. 156.  et al. 2011. Arctigenin efficiently enhanced sedentary mice treadmill endurance. PLoS ONE 6:e24224 [Google Scholar]
  157. Thaler JS, Humphrey PT, Whiteman NK. 157.  2012. Evolution of jasmonate and salicylate signal crosstalk. Trends Plant Sci. 17:260–70 [Google Scholar]
  158. Thelander M, Olsson T, Ronne H. 158.  2004. Snf1-related protein kinase 1 is needed for growth in a normal day-night light cycle. EMBO J. 23:1900–10 [Google Scholar]
  159. Thyagarajan-Sahu A, Lane B, Sliva D. 159.  2011. ReishiMax, mushroom based dietary supplement, inhibits adipocyte differentiation, stimulates glucose uptake and activates AMPK. BMC Complement. Altern. Med. 11:74 [Google Scholar]
  160. Tong X, Smith KA, Pelling JC. 160.  2012. Apigenin, a chemopreventive bioflavonoid, induces AMP-activated protein kinase activation in human keratinocytes. Mol. Carcinog. 51:268–79 [Google Scholar]
  161. Townley R, Shapiro L. 161.  2007. Crystal structures of the adenylate sensor from fission yeast AMP-activated protein kinase. Science 315:1726–29 [Google Scholar]
  162. Tsaousis AD, Kunji ER, Goldberg AV, Lucocq JM, Hirt RP, Embley TM. 162.  2008. A novel route for ATP acquisition by the remnant mitochondria of Encephalitozoon cuniculi. Nature 453:553–56 [Google Scholar]
  163. Tsuda S, Egawa T, Ma X, Oshima R, Kurogi E, Hayashi T. 163.  2012. Coffee polyphenol caffeic acid but not chlorogenic acid increases 5′AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle. J. Nutr. Biochem. 23:1403–9 [Google Scholar]
  164. Tzeng TF, Lu HJ, Liou SS, Chang CJ, Liu IM. 164.  2012. Emodin protects against high-fat diet-induced obesity via regulation of AMP-activated protein kinase pathways in white adipose tissue. Planta Med. 78:943–50 [Google Scholar]
  165. Vane JR. 165.  1971. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat. New Biol. 231:232–35 [Google Scholar]
  166. Vane JR, Botting RM. 166.  2003. The mechanism of action of aspirin. Thromb. Res. 110:255–58 [Google Scholar]
  167. Vincent MF, Marangos PJ, Gruber HE, Van den Berghe G. 167.  1991. Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes. Diabetes 40:1259–66 [Google Scholar]
  168. Wang DS, Jonker JW, Kato Y, Kusuhara H, Schinkel AH, Sugiyama Y. 168.  2002. Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J. Pharmacol. Exp. Ther. 302:510–15 [Google Scholar]
  169. Wang Z, Wilson WA, Fujino MA, Roach PJ. 169.  2001. Antagonistic controls of autophagy and glycogen accumulation by Snf1p, the yeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase Pho85p. Mol. Cell. Biol. 21:5742–52 [Google Scholar]
  170. Willesen MG, Kristensen P, Romer J. 170.  1999. Co-localization of growth hormone secretagogue receptor and NPY mRNA in the arcuate nucleus of the rat. Neuroendocrinology 70:306–16 [Google Scholar]
  171. Winder WW, Hardie DG. 171.  1996. Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am. J. Physiol. 270:E299–304 [Google Scholar]
  172. Woods A, Dickerson K, Heath R, Hong SP, Momcilovic M. 172.  et al. 2005. Ca2+/calmodulin-dependent protein kinase kinase-β acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab. 2:21–33 [Google Scholar]
  173. Wu N, Zheng B, Shaywitz A, Dagon Y, Tower C. 173.  et al. 2013. AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1. Mol. Cell 49:1167–75 [Google Scholar]
  174. Xiao B, Heath R, Saiu P, Leiper FC, Leone P. 174.  et al. 2007. Structural basis for AMP binding to mammalian AMP-activated protein kinase. Nature 449:496–500 [Google Scholar]
  175. Xiao B, Sanders MJ, Carmena D, Bright NJ, Haire LF. 175.  et al. 2013. Structural basis of AMPK regulation by small molecule activators. Nat. Commun. 4:3017 [Google Scholar]
  176. Xiao B, Sanders MJ, Underwood E, Heath R, Mayer FV. 176.  et al. 2011. Structure of mammalian AMPK and its regulation by ADP. Nature 472:230–33 [Google Scholar]
  177. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H. 177.  et al. 2002. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med. 6:1288–95 [Google Scholar]
  178. Yang JM, Hung CM, Fu CN, Lee JC, Huang CH. 178.  et al. 2010. Hispidulin sensitizes human ovarian cancer cells to TRAIL-induced apoptosis by AMPK activation leading to Mcl-1 block in translation. J. Agric. Food Chem. 58:10020–26 [Google Scholar]
  179. Yang Y, Atasoy D, Su HH, Sternson SM. 179.  2011. Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop. Cell 146:992–1003 [Google Scholar]
  180. Yang Z, Kahn BB, Shi H, Xue BZ. 180.  2010. Macrophage alpha1 AMP-activated protein kinase (α1AMPK) antagonizes fatty acid-induced inflammation through SIRT1. J. Biol. Chem. 285:19051–59 [Google Scholar]
  181. Yeh LA, Lee KH, Kim KH. 181.  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. 255:2308–14 [Google Scholar]
  182. Yeung ED, Morrison A, Plumeri D, Wang J, Tong C. 182.  et al. 2012. Alternol exerts prostate-selective antitumor effects through modulations of the AMPK signaling pathway. Prostate 72:165–72 [Google Scholar]
  183. Youn SH, Lee JS, Lee MS, Cha EY, Thuong PT. 183.  et al. 2012. Anticancer properties of pomolic acid-induced AMP-activated protein kinase activation in MCF7 human breast cancer cells. Biol. Pharm. Bull. 35:105–10 [Google Scholar]
  184. Yuan HD, Kim DY, Quan HY, Kim SJ, Jung MS, Chung SH. 184.  2012. Ginsenoside Rg2 induces orphan nuclear receptor SHP gene expression and inactivates GSK3β via AMP-activated protein kinase to inhibit hepatic glucose production in HepG2 cells. Chem.-Biol. Interact. 195:35–42 [Google Scholar]
  185. Zhang YL, Guo H, Zhang CS, Lin SY, Yin Z. 185.  et al. 2013. AMP as a low-energy charge signal autonomously initiates assembly of AXIN-AMPK-LKB1 complex for AMPK activation. Cell Metab. 18:546–55 [Google Scholar]
  186. Zheng QY, Jin FS, Yao C, Zhang T, Zhang GH, Ai X. 186.  2012. Ursolic acid-induced AMP-activated protein kinase (AMPK) activation contributes to growth inhibition and apoptosis in human bladder cancer T24 cells. Biochem. Biophys. Res. Comm. 419:741–47 [Google Scholar]
  187. Zhou G, Myers R, Li Y, Chen Y, Shen X. 187.  et al. 2001. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108:1167–74 [Google Scholar]
  188. Zong H, Ren JM, Young LH, Pypaert M, Mu J. 188.  et al. 2002. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc. Natl. Acad. Sci. USA 99:15983–87 [Google Scholar]
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