Targeting AMPK Signaling in the Liver: Implications for Obesity and Type 2 Diabetes Mellitus

Page: [1057 - 1071] Pages: 15

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Abstract

Obesity and type 2 diabetes mellitus (T2DM), as common metabolic diseases, are pathologically characterized by overnutrition and insulin resistance (IR), which subsequently lead to glucose and lipid metabolism disorders. The liver, a major metabolic organ of the body, integrates hormone and metabolic signals to regulate the synthesis of lipids and glucose as well as their transport to peripheral tissues, hence playing an essential role in the development of obesity and T2DM. Adenosine 5’-monophosphate-activated protein kinase (AMPK) is a central regulator involved in cellular and organismal metabolism in eukaryotes, which activates processes that produce ATP and diminishes its consumption. In addition, AMPK also regulates mitochondrial homeostasis and promotes autophagy, both of which are associated with the pathogenesis of IR. Therefore, increasing AMPK activity is considered a promising therapeutic strategy to prevent obesity and T2DM. In this review, we summarize the role of hepatic AMPK in obesity and T2DM and the potential of using AMPK activators as therapeutics for metabolic disorders.

Keywords: AMPK, obesity, type 2 diabetes mellitus, liver, AMPK activators, hyperglycemia.

Graphical Abstract

[1]
Al-Sulaiti H, Diboun I, Agha MV, et al. Metabolic signature of obesity-associated insulin resistance and type 2 diabetes. J Transl Med 2019; 17(1): 348.
[http://dx.doi.org/10.1186/s12967-019-2096-8] [PMID: 31640727]
[2]
Ortega FB, Lavie CJ, Blair SN. Obesity and cardiovascular disease. Circ Res 2016; 118(11): 1752-70.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306883] [PMID: 27230640]
[3]
Gadde KM, Allison DB. Combination therapy for obesity and metabolic disease. Curr Opin Endocrinol Diabetes Obes 2009; 16(5): 353-8.
[http://dx.doi.org/10.1097/MED.0b013e3283304f90] [PMID: 19625958]
[4]
Pandey A, Chawla S, Guchhait P. Type-2 diabetes: Current understanding and future perspectives. IUBMB Life 2015; 67(7): 506-13.
[http://dx.doi.org/10.1002/iub.1396] [PMID: 26177573]
[5]
Gupta D, Krueger CB, Lastra G. Over-nutrition, obesity and insulin resistance in the development of β-cell dysfunction. Curr Diabetes Rev 2012; 8(2): 76-83.
[http://dx.doi.org/10.2174/157339912799424564] [PMID: 22229253]
[6]
Haas JT, Francque S, Staels B. Pathophysiology and mechanisms of nonalcoholic fatty liver disease. Annu Rev Physiol 2016; 78: 181-205.
[http://dx.doi.org/10.1146/annurev-physiol-021115-105331] [PMID: 26667070]
[7]
Miyajima A, Tanaka M, Itoh T. Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming. Cell Stem Cell 2014; 14(5): 561-74.
[http://dx.doi.org/10.1016/j.stem.2014.04.010] [PMID: 24792114]
[8]
Ding HR, Wang JL, Ren HZ, Shi XL. Lipometabolism and glycometabolism in liver diseases. BioMed Res Int 2018; 2018: 1287127.
[http://dx.doi.org/10.1155/2018/1287127] [PMID: 31205932]
[9]
Carlson CA, Kim KH. Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. J Biol Chem 1973; 248(1): 378-80.
[http://dx.doi.org/10.1016/S0021-9258(19)44486-4] [PMID: 4692841]
[10]
Beg ZH, Allmann DW, Gibson DM. Modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and wth protein fractions of rat liver cytosol. Biochem Biophys Res Commun 1973; 54(4): 1362-9.
[http://dx.doi.org/10.1016/0006-291X(73)91137-6] [PMID: 4356818]
[11]
Munday MR, Campbell DG, Carling D, Hardie DG. Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase. Eur J Biochem 1988; 175(2): 331-8.
[http://dx.doi.org/10.1111/j.1432-1033.1988.tb14201.x] [PMID: 2900138]
[12]
Hardie DG. AMPK: a target for drugs and natural products with effects on both diabetes and cancer. Diabetes 2013; 62(7): 2164-72.
[http://dx.doi.org/10.2337/db13-0368] [PMID: 23801715]
[13]
Ruderman N, Prentki M. AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nat Rev Drug Discov 2004; 3(4): 340-51.
[http://dx.doi.org/10.1038/nrd1344] [PMID: 15060529]
[14]
Hoppe S, Bierhoff H, Cado I, et al. AMP-activated protein kinase adapts rRNA synthesis to cellular energy supply. Proc Natl Acad Sci USA 2009; 106(42): 17781-6.
[http://dx.doi.org/10.1073/pnas.0909873106] [PMID: 19815529]
[15]
Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 2005; 1(1): 15-25.
[http://dx.doi.org/10.1016/j.cmet.2004.12.003] [PMID: 16054041]
[16]
Yang F, Qin Y, Wang Y, et al. Metformin inhibits the NLRP3 inflammasome via AMPK/mTOR-dependent effects in diabetic cardiomyopathy. Int J Biol Sci 2019; 15(5): 1010-9.
[http://dx.doi.org/10.7150/ijbs.29680] [PMID: 31182921]
[17]
Akhtar S, Siragy HM. Pro-renin receptor suppresses mitochondrial biogenesis and function via AMPK/SIRT-1/PGC-1α pathway in diabetic kidney. PLoS One 2019; 14(12): e0225728.
[http://dx.doi.org/10.1371/journal.pone.0225728] [PMID: 31800607]
[18]
Dzamko N, van Denderen BJ, Hevener AL, et al. AMPK beta1 deletion reduces appetite, preventing obesity and hepatic insulin resistance. J Biol Chem 2010; 285(1): 115-22.
[http://dx.doi.org/10.1074/jbc.M109.056762] [PMID: 19892703]
[19]
Jung TW, Lee SH, Kim HC, et al. METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice. Exp Mol Med 2018; 50(9): 1-11.
[http://dx.doi.org/10.1038/s12276-018-0147-5] [PMID: 30213948]
[20]
Garcia D, Shaw RJ. AMPK: mechanisms of cellular energy sensing and restoration of metabolic balance. Mol Cell 2017; 66(6): 789-800.
[http://dx.doi.org/10.1016/j.molcel.2017.05.032] [PMID: 28622524]
[21]
Li YH, Luo J, Mosley YY, et al. AMP-activated protein kinase directly phosphorylates and destabilizes Hedgehog pathway transcription factor GLI1 in medulloblastoma. Cell Rep 2015; 12(4): 599-609.
[http://dx.doi.org/10.1016/j.celrep.2015.06.054] [PMID: 26190112]
[22]
Lamia KA, Sachdeva UM, DiTacchio L, et al. AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 2009; 326(5951): 437-40.
[http://dx.doi.org/10.1126/science.1172156] [PMID: 19833968]
[23]
Hardie DG. AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev 2011; 25(18): 1895-908.
[http://dx.doi.org/10.1101/gad.17420111] [PMID: 21937710]
[24]
Ruderman NB, Carling D, Prentki M, Cacicedo JM. AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest 2013; 123(7): 2764-72.
[http://dx.doi.org/10.1172/JCI67227] [PMID: 23863634]
[25]
Salminen A, Hyttinen JM, Kaarniranta K. AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan. J Mol Med (Berl) 2011; 89(7): 667-76.
[http://dx.doi.org/10.1007/s00109-011-0748-0] [PMID: 21431325]
[26]
Jeon SM, Chandel NS, Hay N. AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 2012; 485(7400): 661-5.
[http://dx.doi.org/10.1038/nature11066] [PMID: 22660331]
[27]
Mack HI, Zheng B, Asara JM, Thomas SM. AMPK-dependent phosphorylation of ULK1 regulates ATG9 localization. Autophagy 2012; 8(8): 1197-214.
[http://dx.doi.org/10.4161/auto.20586] [PMID: 22932492]
[28]
Hardie DG, Schaffer BE, Brunet A. AMPK: An energy-sensing pathway with multiple inputs and outputs. Trends Cell Biol 2016; 26(3): 190-201.
[http://dx.doi.org/10.1016/j.tcb.2015.10.013] [PMID: 26616193]
[29]
Ross FA, MacKintosh C, Hardie DG. AMP-activated protein kinase: a cellular energy sensor that comes in 12 flavours. FEBS J 2016; 283(16): 2987-3001.
[http://dx.doi.org/10.1111/febs.13698] [PMID: 26934201]
[30]
Hawley SA, Davison M, Woods A, et al. Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. J Biol Chem 1996; 271(44): 27879-87.
[http://dx.doi.org/10.1074/jbc.271.44.27879] [PMID: 8910387]
[31]
Chen L, Jiao ZH, Zheng LS, et al. Structural insight into the autoinhibition mechanism of AMP-activated protein kinase. Nature 2009; 459(7250): 1146-9.
[http://dx.doi.org/10.1038/nature08075] [PMID: 19474788]
[32]
Xin FJ, Wang J, Zhao RQ, Wang ZX, Wu JW. Coordinated regulation of AMPK activity by multiple elements in the α-subunit. Cell Res 2013; 23(10): 1237-40.
[http://dx.doi.org/10.1038/cr.2013.121] [PMID: 23999859]
[33]
Dyck JR, Gao G, Widmer J, et al. Regulation of 5′-AMP-activated protein kinase activity by the noncatalytic beta and gamma subunits. J Biol Chem 1996; 271(30): 17798-803.
[http://dx.doi.org/10.1074/jbc.271.30.17798] [PMID: 8663446]
[34]
Chandrashekarappa DG, McCartney RR, Schmidt MC. Subunit and domain requirements for adenylate-mediated protection of Snf1 kinase activation loop from dephosphorylation. J Biol Chem 2011; 286(52): 44532-41.
[http://dx.doi.org/10.1074/jbc.M111.315895] [PMID: 22065577]
[35]
Warden SM, Richardson C, O’Donnell J Jr, Stapleton D, Kemp BE, Witters LA. Post-translational modifications of the beta-1 subunit of AMP-activated protein kinase affect enzyme activity and cellular localization. Biochem J 2001; 354(Pt 2): 275-83.
[http://dx.doi.org/10.1042/bj3540275] [PMID: 11171104]
[36]
Hoffman NJ, Whitfield J, Janzen NR, et al. Genetic loss of AMPK-glycogen binding destabilises AMPK and disrupts metabolism. Mol Metab 2020; 41: 101048.
[http://dx.doi.org/10.1016/j.molmet.2020.101048] [PMID: 32610071]
[37]
Yan Y, Zhou XE, Xu HE, Melcher K. Structure and physiological regulation of AMPK. Int J Mol Sci 2018; 19(11): 3534.
[http://dx.doi.org/10.3390/ijms19113534] [PMID: 30423971]
[38]
Xiao B, Heath R, Saiu P, et al. Structural basis for AMP binding to mammalian AMP-activated protein kinase. Nature 2007; 449(7161): 496-500.
[http://dx.doi.org/10.1038/nature06161] [PMID: 17851531]
[39]
Pelosse M, Cottet-Rousselle C, Bidan CM, et al. Synthetic energy sensor AMPfret deciphers adenylate-dependent AMPK activation mechanism. Nat Commun 2019; 10(1): 1038.
[http://dx.doi.org/10.1038/s41467-019-08938-z] [PMID: 30833561]
[40]
Gowans GJ, Hawley SA, Ross FA, Hardie DG. AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab 2013; 18(4): 556-66.
[http://dx.doi.org/10.1016/j.cmet.2013.08.019] [PMID: 24093679]
[41]
Hawley SA, Boudeau J, Reid JL, et al. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol 2003; 2(4): 28.
[http://dx.doi.org/10.1186/1475-4924-2-28] [PMID: 14511394]
[42]
Woods A, Dickerson K, Heath R, et al. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab 2005; 2(1): 21-33.
[http://dx.doi.org/10.1016/j.cmet.2005.06.005] [PMID: 16054096]
[43]
Xie M, Zhang D, Dyck JR, et al. A pivotal role for endogenous TGF-beta-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway. Proc Natl Acad Sci USA 2006; 103(46): 17378-83.
[http://dx.doi.org/10.1073/pnas.0604708103] [PMID: 17085580]
[44]
Davies SP, Helps NR, Cohen PT, Hardie DG. 5′-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC. FEBS Lett 1995; 377(3): 421-5.
[http://dx.doi.org/10.1016/0014-5793(95)01368-7] [PMID: 8549768]
[45]
Voss M, Paterson J, Kelsall IR, et al. Ppm1E is an in cellulo AMP-activated protein kinase phosphatase. Cell Signal 2011; 23(1): 114-24.
[http://dx.doi.org/10.1016/j.cellsig.2010.08.010] [PMID: 20801214]
[46]
Oakhill JS, Chen ZP, Scott JW, et al. β-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK). Proc Natl Acad Sci USA 2010; 107(45): 19237-41.
[http://dx.doi.org/10.1073/pnas.1009705107] [PMID: 20974912]
[47]
Jin L, Chun J, Pan C, et al. The PLAG1-GDH1 axis promotes anoikis resistance and tumor metastasis through CamKK2-AMPK signaling in LKB1-deficient lung cancer. Mol Cell 2018; 69(1): 87-99.e7.
[http://dx.doi.org/10.1016/j.molcel.2017.11.025] [PMID: 29249655]
[48]
Momcilovic M, Hong SP, Carlson M. Mammalian TAK1 activates Snf1 protein kinase in yeast and phosphorylates AMP-activated protein kinase in vitro. J Biol Chem 2006; 281(35): 25336-43.
[http://dx.doi.org/10.1074/jbc.M604399200] [PMID: 16835226]
[49]
Hardie DG. AMPK--sensing energy while talking to other signaling pathways. Cell Metab 2014; 20(6): 939-52.
[http://dx.doi.org/10.1016/j.cmet.2014.09.013] [PMID: 25448702]
[50]
Hurley RL, Barré LK, Wood SD, et al. Regulation of AMP-activated protein kinase by multisite phosphorylation in response to agents that elevate cellular cAMP. J Biol Chem 2006; 281(48): 36662-72.
[http://dx.doi.org/10.1074/jbc.M606676200] [PMID: 17023420]
[51]
Dagon Y, Hur E, Zheng B, Wellenstein K, Cantley LC, Kahn BB. p70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin’s effect on food intake. Cell Metab 2012; 16(1): 104-12.
[http://dx.doi.org/10.1016/j.cmet.2012.05.010] [PMID: 22727014]
[52]
Suzuki T, Bridges D, Nakada D, et al. Inhibition of AMPK catabolic action by GSK3. Mol Cell 2013; 50(3): 407-19.
[http://dx.doi.org/10.1016/j.molcel.2013.03.022] [PMID: 23623684]
[53]
Coughlan KA, Valentine RJ, Sudit BS, et al. PKD1 inhibits AMPKalpha2 through phosphorylation of serine 491 and impairs insulin signaling in skeletal muscle cells. J Biol Chem 2016; 291(11): 5664-75.
[http://dx.doi.org/10.1074/jbc.M115.696849] [PMID: 26797128]
[54]
Heathcote HR, Mancini SJ, Strembitska A, et al. Protein kinase C phosphorylates AMP-activated protein kinase α1 Ser487. Biochem J 2016; 473(24): 4681-97.
[http://dx.doi.org/10.1042/BCJ20160211] [PMID: 27784766]
[55]
Zmijewski JW, Banerjee S, Bae H, Friggeri A, Lazarowski ER, Abraham E. Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase. J Biol Chem 2010; 285(43): 33154-64.
[http://dx.doi.org/10.1074/jbc.M110.143685] [PMID: 20729205]
[56]
Horie T, Ono K, Nagao K, et al. Oxidative stress induces GLUT4 translocation by activation of PI3-K/Akt and dual AMPK kinase in cardiac myocytes. J Cell Physiol 2008; 215(3): 733-42.
[http://dx.doi.org/10.1002/jcp.21353] [PMID: 18163380]
[57]
Irrcher I, Ljubicic V, Hood DA. Interactions between ROS and AMP kinase activity in the regulation of PGC-1alpha transcription in skeletal muscle cells. Am J Physiol Cell Physiol 2009; 296(1): C116-23.
[http://dx.doi.org/10.1152/ajpcell.00267.2007] [PMID: 19005163]
[58]
Shao D, Oka S, Liu T, et al. A redox-dependent mechanism for regulation of AMPK activation by Thioredoxin1 during energy starvation. Cell Metab 2014; 19(2): 232-45.
[http://dx.doi.org/10.1016/j.cmet.2013.12.013] [PMID: 24506865]
[59]
Mouchiroud L, Eichner LJ, Shaw RJ, Auwerx J. Transcriptional coregulators: fine-tuning metabolism. Cell Metab 2014; 20(1): 26-40.
[http://dx.doi.org/10.1016/j.cmet.2014.03.027] [PMID: 24794975]
[60]
Esquejo RM, Salatto CT, Delmore J, et al. Activation of liver AMPK with PF-06409577 corrects NAFLD and lowers cholesterol in rodent and primate preclinical models. EBioMedicine 2018; 31: 122-32.
[http://dx.doi.org/10.1016/j.ebiom.2018.04.009] [PMID: 29673898]
[61]
DeRan M, Yang J, Shen CH, et al. Energy stress regulates hippo-YAP signaling involving AMPK-mediated regulation of angiomotin-like 1 protein. Cell Rep 2014; 9(2): 495-503.
[http://dx.doi.org/10.1016/j.celrep.2014.09.036] [PMID: 25373897]
[62]
Mo JS, Meng Z, Kim YC, et al. Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway. Nat Cell Biol 2015; 17(4): 500-10.
[http://dx.doi.org/10.1038/ncb3111] [PMID: 25751140]
[63]
Wang W, Xiao ZD, Li X, et al. AMPK modulates Hippo pathway activity to regulate energy homeostasis. Nat Cell Biol 2015; 17(4): 490-9.
[http://dx.doi.org/10.1038/ncb3113] [PMID: 25751139]
[64]
Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003; 115(5): 577-90.
[http://dx.doi.org/10.1016/S0092-8674(03)00929-2] [PMID: 14651849]
[65]
Gwinn DM, Shackelford DB, Egan DF, et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 2008; 30(2): 214-26.
[http://dx.doi.org/10.1016/j.molcel.2008.03.003] [PMID: 18439900]
[66]
Leprivier G, Remke M, Rotblat B, et al. The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. Cell 2013; 153(5): 1064-79.
[http://dx.doi.org/10.1016/j.cell.2013.04.055] [PMID: 23706743]
[67]
Cho E, Kwon M, Jung J, et al. Jung J., Kang D. H., Jin S., Choi S. E., Kang Y., and Kim E. Y. AMP-activated protein kinase regulates circadian rhythm by affecting CLOCK in drosophila. J Neurosci 2019; 39(18): 3537-50.
[http://dx.doi.org/10.1523/JNEUROSCI.2344-18.2019] [PMID: 30819799]
[68]
Vieira E, Nilsson EC, Nerstedt A, et al. Relationship between AMPK and the transcriptional balance of clock-related genes in skeletal muscle. Am J Physiol Endocrinol Metab 2008; 295(5): E1032-7.
[http://dx.doi.org/10.1152/ajpendo.90510.2008] [PMID: 18728219]
[69]
Um JH, Yang S, Yamazaki S, et al. Activation of 5′-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2. J Biol Chem 2007; 282(29): 20794-8.
[http://dx.doi.org/10.1074/jbc.C700070200] [PMID: 17525164]
[70]
Wu H, Deng X, Shi Y, Su Y, Wei J, Duan H. PGC-1α, glucose metabolism and type 2 diabetes mellitus. J Endocrinol 2016; 229(3): R99-R115.
[http://dx.doi.org/10.1530/JOE-16-0021] [PMID: 27094040]
[71]
Yang X, Liu Q, Li Y, et al. The diabetes medication canagliflozin promotes mitochondrial remodelling of adipocyte via the AMPK-Sirt1-Pgc-1α signalling pathway. Adipocyte 2020; 9(1): 484-94.
[http://dx.doi.org/10.1080/21623945.2020.1807850] [PMID: 32835596]
[72]
Jäger S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 2007; 104(29): 12017-22.
[http://dx.doi.org/10.1073/pnas.0705070104] [PMID: 17609368]
[73]
Toyama EQ, Herzig S, Courchet J, et al. Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Science 2016; 351(6270): 275-81.
[http://dx.doi.org/10.1126/science.aab4138] [PMID: 26816379]
[74]
Balakrishnan BB, Krishnasamy K, Mayakrishnan V, Selvaraj A. Moringa concanensis Nimmo extracts ameliorates hyperglycemia-mediated oxidative stress and upregulates PPARγ and GLUT4 gene expression in liver and pancreas of streptozotocin-nicotinamide induced diabetic rats. Biomed Pharmacother 2019; 112: 108688.
[http://dx.doi.org/10.1016/j.biopha.2019.108688] [PMID: 30798121]
[75]
Muoio DM, Seefeld K, Witters LA, Coleman RA. 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 1999; 338(Pt 3): 783-91.
[http://dx.doi.org/10.1042/bj3380783] [PMID: 10051453]
[76]
Laker RC, Drake JC, Wilson RJ, et al. Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy. Nat Commun 2017; 8(1): 548.
[http://dx.doi.org/10.1038/s41467-017-00520-9] [PMID: 28916822]
[77]
Liu J, Long S, Wang H, et al. Blocking AMPK/ULK1-dependent autophagy promoted apoptosis and suppressed colon cancer growth. Cancer Cell Int 2019; 19: 336.
[http://dx.doi.org/10.1186/s12935-019-1054-0] [PMID: 31871431]
[78]
Cool B, Zinker B, Chiou W, et al. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab 2006; 3(6): 403-16.
[http://dx.doi.org/10.1016/j.cmet.2006.05.005] [PMID: 16753576]
[79]
Li Y, Xu S, Mihaylova MM, et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab 2011; 13(4): 376-88.
[http://dx.doi.org/10.1016/j.cmet.2011.03.009] [PMID: 21459323]
[80]
Hardie DG, Pan DA. Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase. Biochem Soc Trans 2002; 30(Pt 6): 1064-70.
[http://dx.doi.org/10.1042/bst0301064] [PMID: 12440973]
[81]
Yuan E, Duan X, Xiang L, et al. Aged Oolong Tea reduces high-fat diet-induced fat accumulation and dyslipidemia by regulating the AMPK/ACC signaling pathway. Nutrients 2018; 10(2): 187.
[http://dx.doi.org/10.3390/nu10020187] [PMID: 29419789]
[82]
Zhang Y, Liu M, Chen Q, et al. Leaves of Lippia triphylla improve hepatic lipid metabolism via activating AMPK to regulate lipid synthesis and degradation. J Nat Med 2019; 73(4): 707-16.
[http://dx.doi.org/10.1007/s11418-019-01316-5] [PMID: 31104252]
[83]
Zhu X, Bian H, Wang L, et al. Berberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway. Free Radic Biol Med 2019; 141: 192-204.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.06.019] [PMID: 31226399]
[84]
González A, Hall MN, Lin SC, Hardie DG. AMPK and TOR: The Yin and Yang of cellular nutrient sensing and growth control. Cell Metab 2020; 31(3): 472-92.
[http://dx.doi.org/10.1016/j.cmet.2020.01.015] [PMID: 32130880]
[85]
Han J, Wang Y. mTORC1 signaling in hepatic lipid metabolism. Protein Cell 2018; 9(2): 145-51.
[http://dx.doi.org/10.1007/s13238-017-0409-3] [PMID: 28434145]
[86]
Li H, Min Q, Ouyang C, et al. AMPK activation prevents excess nutrient-induced hepatic lipid accumulation by inhibiting mTORC1 signaling and endoplasmic reticulum stress response. Biochim Biophys Acta 2014; 1842(9): 1844-54.
[http://dx.doi.org/10.1016/j.bbadis.2014.07.002] [PMID: 25016145]
[87]
Niu Y, Li S, Na L, et al. Mangiferin decreases plasma free fatty acids through promoting its catabolism in liver by activation of AMPK. PLoS One 2012; 7(1): e30782.
[http://dx.doi.org/10.1371/journal.pone.0030782] [PMID: 22292039]
[88]
McGarry JD, Leatherman GF, Foster DW. Carnitine palmitoyltransferase I. The site of inhibition of hepatic fatty acid oxidation by malonyl-CoA. J Biol Chem 1978; 253(12): 4128-36.
[http://dx.doi.org/10.1016/S0021-9258(17)34693-8] [PMID: 659409]
[89]
Brunt EM, Wong VW, Nobili V, et al. Nonalcoholic fatty liver disease. Nat Rev Dis Primers 2015; 1: 15080.
[http://dx.doi.org/10.1038/nrdp.2015.80] [PMID: 27188459]
[90]
Reza HM, Tabassum N, Sagor MA, et al. Angiotensin-converting enzyme inhibitor prevents oxidative stress, inflammation, and fibrosis in carbon tetrachloride-treated rat liver. Toxicol Mech Methods 2016; 26(1): 46-53.
[http://dx.doi.org/10.3109/15376516.2015.1124956] [PMID: 26862777]
[91]
Reza HM, Sagor MAT, Alam MA. Iron deposition causes oxidative stress, inflammation and fibrosis in carbon tetrachloride-induced liver dysfunction in rats. Bangladesh J Pharmacol 2015; 10(1): 152-9.
[http://dx.doi.org/10.3329/bjp.v10i1.21711]
[92]
Huang BP, Lin CH, Chen HM, Lin JT, Cheng YF, Kao SH. AMPK activation inhibits expression of proinflammatory mediators through downregulation of PI3K/p38 MAPK and NF-κB signaling in murine macrophages. DNA Cell Biol 2015; 34(2): 133-41.
[http://dx.doi.org/10.1089/dna.2014.2630] [PMID: 25536376]
[93]
O’Neill LA, Hardie DG. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 2013; 493(7432): 346-55.
[http://dx.doi.org/10.1038/nature11862] [PMID: 23325217]
[94]
Zhao P, Wong KI, Sun X, et al. TBK1 at the crossroads of inflammation and energy homeostasis in adipose tissue. Cell 2018; 172(4): 731-743.e12.
[http://dx.doi.org/10.1016/j.cell.2018.01.007] [PMID: 29425491]
[95]
Al-Rasadi K, Rizzo M, Montalto G, Berg G. Nonalcoholic fatty liver disease, cardiovascular risk, and carotid inflammation. Angiology 2015; 66(7): 601-3.
[http://dx.doi.org/10.1177/0003319714557353] [PMID: 25381142]
[96]
Win S, Than TA, Zhang J, Oo C, Min RWM, Kaplowitz N. New insights into the role and mechanism of c-Jun-N-terminal kinase signaling in the pathobiology of liver diseases. Hepatology 2018; 67(5): 2013-24.
[http://dx.doi.org/10.1002/hep.29689] [PMID: 29194686]
[97]
Luedde T, Schwabe RF. NF-κB in the liver--linking injury, fibrosis and hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2011; 8(2): 108-18.
[http://dx.doi.org/10.1038/nrgastro.2010.213] [PMID: 21293511]
[98]
Yeung F, Hoberg JE, Ramsey CS, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 2004; 23(12): 2369-80.
[http://dx.doi.org/10.1038/sj.emboj.7600244] [PMID: 15152190]
[99]
Xiong Y, Torsoni AS, Wu F, et al. Hepatic NF-kB-inducing kinase (NIK) suppresses mouse liver regeneration in acute and chronic liver diseases. eLife 2018; 7: e34152.
[http://dx.doi.org/10.7554/eLife.34152] [PMID: 30070632]
[100]
Mancini SJ, White AD, Bijland S, et al. Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation. Mol Cell Endocrinol 2017; 440: 44-56.
[http://dx.doi.org/10.1016/j.mce.2016.11.010] [PMID: 27840174]
[101]
Rabinovitch RC, Samborska B, Faubert B, et al. AMPK maintains cellular metabolic homeostasis through regulation of mitochondrial reactive oxygen species. Cell Rep 2017; 21(1): 1-9.
[http://dx.doi.org/10.1016/j.celrep.2017.09.026] [PMID: 28978464]
[102]
Wang S, Zhang M, Liang B, et al. AMPKalpha2 deletion causes aberrant expression and activation of NAD(P)H oxidase and consequent endothelial dysfunction in vivo: role of 26S proteasomes. Circ Res 2010; 106(6): 1117-28.
[http://dx.doi.org/10.1161/CIRCRESAHA.109.212530] [PMID: 20167927]
[103]
Eid AA, Ford BM, Block K, et al. AMP-activated protein kinase (AMPK) negatively regulates Nox4-dependent activation of p53 and epithelial cell apoptosis in diabetes. J Biol Chem 2010; 285(48): 37503-12.
[http://dx.doi.org/10.1074/jbc.M110.136796] [PMID: 20861022]
[104]
Song P, Zou MH. Regulation of NAD(P)H oxidases by AMPK in cardiovascular systems. Free Radic Biol Med 2012; 52(9): 1607-19.
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.01.025] [PMID: 22357101]
[105]
Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol 2010; 11(2): 136-40.
[http://dx.doi.org/10.1038/ni.1831] [PMID: 20023662]
[106]
Chadt A, Al-Hasani H. Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease. Pflugers Arch 2020; 472(9): 1273-98.
[http://dx.doi.org/10.1007/s00424-020-02417-x] [PMID: 32591906]
[107]
Guillam MT, Burcelin R, Thorens B. Normal hepatic glucose production in the absence of GLUT2 reveals an alternative pathway for glucose release from hepatocytes. Proc Natl Acad Sci USA 1998; 95(21): 12317-21.
[http://dx.doi.org/10.1073/pnas.95.21.12317] [PMID: 9770484]
[108]
Zhu D, Yan Q, Li Y, Liu J, Liu H, Jiang Z. Effect of konjac mannan oligosaccharides on glucose homeostasis via the improvement of insulin and leptin resistance in vitro and in vivo. Nutrients 2019; 11(8): E1705.
[http://dx.doi.org/10.3390/nu11081705] [PMID: 31344867]
[109]
Li Q, Wang Y, Cai G, et al. Antifatigue activity of liquid cultured tricholoma matsutake mycelium partially via regulation of antioxidant pathway in mouse. BioMed Res Int 2015; 2015: 562345.
[http://dx.doi.org/10.1155/2015/562345] [PMID: 26697489]
[110]
Ha do T, Trung TN, Hien TT, et al. Selected compounds derived from Moutan Cortex stimulated glucose uptake and glycogen synthesis via AMPK activation in human HepG2 cells. J Ethnopharmacol 2010; 131(2): 417-24.
[http://dx.doi.org/10.1016/j.jep.2010.07.010] [PMID: 20633632]
[111]
Koo SH, Flechner L, Qi L, et al. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 2005; 437(7062): 1109-11.
[http://dx.doi.org/10.1038/nature03967] [PMID: 16148943]
[112]
Boustead JN, Stadelmaier BT, Eeds AM, et al. Hepatocyte nuclear factor-4 alpha mediates the stimulatory effect of peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1 alpha) on glucose-6-phosphatase catalytic subunit gene transcription in H4IIE cells. Biochem J 2003; 369(Pt 1): 17-22.
[http://dx.doi.org/10.1042/bj20021382] [PMID: 12416993]
[113]
Mihaylova MM, Vasquez DS, Ravnskjaer K, et al. Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis. Cell 2011; 145(4): 607-21.
[http://dx.doi.org/10.1016/j.cell.2011.03.043] [PMID: 21565617]
[114]
Chen X, Chen S, Shen T, et al. Adropin regulates hepatic glucose production via PP2A/AMPK pathway in insulin-resistant hepatocytes. FASEB J 2020; 34(8): 10056-72.
[http://dx.doi.org/10.1096/fj.202000115RR] [PMID: 32579277]
[115]
Ueno T, Komatsu M. Autophagy in the liver: functions in health and disease. Nat Rev Gastroenterol Hepatol 2017; 14(3): 170-84.
[http://dx.doi.org/10.1038/nrgastro.2016.185] [PMID: 28053338]
[116]
Rogov V, Dötsch V, Johansen T, Kirkin V. Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Mol Cell 2014; 53(2): 167-78.
[http://dx.doi.org/10.1016/j.molcel.2013.12.014] [PMID: 24462201]
[117]
Jiang S, Heller B, Tagliabracci VS, et al. Starch binding domain-containing protein 1/genethonin 1 is a novel participant in glycogen metabolism. J Biol Chem 2010; 285(45): 34960-71.
[http://dx.doi.org/10.1074/jbc.M110.150839] [PMID: 20810658]
[118]
Singh R, Kaushik S, Wang Y, et al. Autophagy regulates lipid metabolism. Nature 2009; 458(7242): 1131-5.
[http://dx.doi.org/10.1038/nature07976] [PMID: 19339967]
[119]
Liang S, Zhong Z, Kim SY, et al. Murine macrophage autophagy protects against alcohol-induced liver injury by degrading interferon regulatory factor 1 (IRF1) and removing damaged mitochondria. J Biol Chem 2019; 294(33): 12359-69.
[http://dx.doi.org/10.1074/jbc.RA119.007409] [PMID: 31235522]
[120]
Liu TY, Xiong XQ, Ren XS, et al. FNDC5 alleviates hepatosteatosis by restoring AMPK/mTOR-mediated autophagy, fatty acid oxidation, and lipogenesis in mice. Diabetes 2016; 65(11): 3262-75.
[http://dx.doi.org/10.2337/db16-0356] [PMID: 27504012]
[121]
Schulze RJ, Sathyanarayan A, Mashek DG. Breaking fat: The regulation and mechanisms of lipophagy. Biochim Biophys Acta Mol Cell Biol Lipids 2017; 1862(10 Pt B): 1178-87.
[http://dx.doi.org/10.1016/j.bbalip.2017.06.008] [PMID: 28642194]
[122]
Liu HY, Han J, Cao SY, et al. Hepatic autophagy is suppressed in the presence of insulin resistance and hyperinsulinemia: inhibition of FoxO1-dependent expression of key autophagy genes by insulin. J Biol Chem 2009; 284(45): 31484-92.
[http://dx.doi.org/10.1074/jbc.M109.033936] [PMID: 19758991]
[123]
Kim SH, Kim G, Han DH, et al. Ezetimibe ameliorates steatohepatitis via AMP activated protein kinase-TFEB-mediated activation of autophagy and NLRP3 inflammasome inhibition. Autophagy 2017; 13(10): 1767-81.
[http://dx.doi.org/10.1080/15548627.2017.1356977] [PMID: 28933629]
[124]
Yang L, Li P, Fu S, Calay ES, Hotamisligil GS. Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab 2010; 11(6): 467-78.
[http://dx.doi.org/10.1016/j.cmet.2010.04.005] [PMID: 20519119]
[125]
Egan DF, Shackelford DB, Mihaylova MM, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 2011; 331(6016): 456-61.
[http://dx.doi.org/10.1126/science.1196371] [PMID: 21205641]
[126]
Liu H, Dong J, Song S, et al. Spermidine ameliorates liver ischaemia-reperfusion injury through the regulation of autophagy by the AMPK-mTOR-ULK1 signalling pathway. Biochem Biophys Res Commun 2019; 519(2): 227-33.
[http://dx.doi.org/10.1016/j.bbrc.2019.08.162] [PMID: 31493865]
[127]
Ren H, Wang D, Zhang L, et al. Catalpol induces autophagy and attenuates liver steatosis in ob/ob and high-fat diet-induced obese mice. Aging (Albany NY) 2019; 11(21): 9461-77.
[http://dx.doi.org/10.18632/aging.102396] [PMID: 31697646]
[128]
Zhao Y, Wang Q, Qiu G, et al. RACK1 Promotes Autophagy by enhancing the Atg14L-Beclin 1-Vps34-Vps15 complex formation upon phosphorylation by AMPK. Cell Rep 2015; 13(7): 1407-17.
[http://dx.doi.org/10.1016/j.celrep.2015.10.011] [PMID: 26549445]
[129]
Masouminia M, Samadzadeh S, Mendoza AS, French BA, Tillman B, French SW. Upregulation of autophagy components in alcoholic hepatitis and nonalcoholic steatohepatitis. Exp Mol Pathol 2016; 101(1): 81-8.
[http://dx.doi.org/10.1016/j.yexmp.2016.07.002] [PMID: 27432584]
[130]
Alimujiang M, Yu XY, Yu MY, et al. Enhanced liver but not muscle OXPHOS in diabetes and reduced glucose output by complex I inhibition. J Cell Mol Med 2020; 24(10): 5758-71.
[http://dx.doi.org/10.1111/jcmm.15238] [PMID: 32253813]
[131]
Fang K, Wu F, Chen G, et al. Diosgenin ameliorates palmitic acid-induced lipid accumulation via AMPK/ACC/CPT-1A and SREBP-1c/FAS signaling pathways in LO2 cells. BMC Complement Altern Med 2019; 19(1): 255.
[http://dx.doi.org/10.1186/s12906-019-2671-9] [PMID: 31519174]
[132]
Mansouri A, Gattolliat CH, Asselah T. Mitochondrial dysfunction and signaling in chronic liver diseases. Gastroenterology 2018; 155(3): 629-47.
[http://dx.doi.org/10.1053/j.gastro.2018.06.083] [PMID: 30012333]
[133]
Luan G, Li G, Ma X, et al. Dexamethasone-induced mitochondrial dysfunction and insulin resistance-study in 3T3-L1 adipocytes and mitochondria isolated from mouse liver. Molecules 2019; 24(10): 1982.
[http://dx.doi.org/10.3390/molecules24101982] [PMID: 31126054]
[134]
Silva J, Spatz MH, Folk C, et al. Dihydromyricetin improves mitochondrial outcomes in the liver of alcohol-fed mice via the AMPK/Sirt-1/PGC-1α signaling axis. Alcohol 2021; 91: 1-9.
[http://dx.doi.org/10.1016/j.alcohol.2020.10.002] [PMID: 33080338]
[135]
Wang SW, Sheng H, Bai YF, et al. Neohesperidin enhances PGC-1α-mediated mitochondrial biogenesis and alleviates hepatic steatosis in high fat diet fed mice. Nutr Diabetes 2020; 10(1): 27.
[http://dx.doi.org/10.1038/s41387-020-00130-3] [PMID: 32759940]
[136]
Zhang Z, Zhou S, Jiang X, et al. The role of the Nrf2/Keap1 pathway in obesity and metabolic syndrome. Rev Endocr Metab Disord 2015; 16(1): 35-45.
[http://dx.doi.org/10.1007/s11154-014-9305-9] [PMID: 25540093]
[137]
Uruno A, Yagishita Y, Yamamoto M. The Keap1-Nrf2 system and diabetes mellitus. Arch Biochem Biophys 2015; 566: 76-84.
[http://dx.doi.org/10.1016/j.abb.2014.12.012] [PMID: 25528168]
[138]
Corton JM, Gillespie JG, Hawley SA, Hardie DG. 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem 1995; 229(2): 558-65.
[http://dx.doi.org/10.1111/j.1432-1033.1995.tb20498.x] [PMID: 7744080]
[139]
Vincent MF, Marangos PJ, Gruber HE, Van den Berghe G. Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes. Diabetes 1991; 40(10): 1259-66.
[http://dx.doi.org/10.2337/diab.40.10.1259] [PMID: 1657665]
[140]
Suwa M, Nakano H, Radak Z, Kumagai S. Short-term adenosine monophosphate-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside treatment increases the sirtuin 1 protein expression in skeletal muscle. Metabolism 2011; 60(3): 394-403.
[http://dx.doi.org/10.1016/j.metabol.2010.03.003] [PMID: 20362304]
[141]
Kim MS, Kewalramani G, Puthanveetil P, et al. Acute diabetes moderates trafficking of cardiac lipoprotein lipase through p38 mitogen-activated protein kinase-dependent actin cytoskeleton organization. Diabetes 2008; 57(1): 64-76.
[http://dx.doi.org/10.2337/db07-0832] [PMID: 17942824]
[142]
Gaidhu MP, Bikopoulos G, Ceddia RB. Chronic AICAR-induced AMP-kinase activation regulates adipocyte lipolysis in a time-dependent and fat depot-specific manner in rats. Am J Physiol Cell Physiol 2012; 303(11): C1192-7.
[http://dx.doi.org/10.1152/ajpcell.00159.2012] [PMID: 23054058]
[143]
Foretz M, Ancellin N, Andreelli F, et al. Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes 2005; 54(5): 1331-9.
[http://dx.doi.org/10.2337/diabetes.54.5.1331] [PMID: 15855317]
[144]
Tomita K, Tamiya G, Ando S, et al. AICAR, an AMPK activator, has protective effects on alcohol-induced fatty liver in rats. Alcohol Clin Exp Res 2005; 29(12)(Suppl.): 240S-5S.
[http://dx.doi.org/10.1097/01.alc.0000191126.11479.69] [PMID: 16385230]
[145]
Boon H, Bosselaar M, Praet SF, et al. Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients. Diabetologia 2008; 51(10): 1893-900.
[http://dx.doi.org/10.1007/s00125-008-1108-7] [PMID: 18709353]
[146]
Cuthbertson DJ, Babraj JA, Mustard KJ, et al. 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes 2007; 56(8): 2078-84.
[http://dx.doi.org/10.2337/db06-1716] [PMID: 17513706]
[147]
Ford RJ, Fullerton MD, Pinkosky SL, et al. Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity. Biochem J 2015; 468(1): 125-32.
[http://dx.doi.org/10.1042/BJ20150125] [PMID: 25742316]
[148]
Jung TW, Youn BS, Choi HY, et al. Salsalate and adiponectin ameliorate hepatic steatosis by inhibition of the hepatokine fetuin-A. Biochem Pharmacol 2013; 86(7): 960-9.
[http://dx.doi.org/10.1016/j.bcp.2013.07.034] [PMID: 23948064]
[149]
Goldfine AB, Silver R, Aldhahi W, et al. Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci 2008; 1(1): 36-43.
[http://dx.doi.org/10.1111/j.1752-8062.2008.00026.x] [PMID: 19337387]
[150]
Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001; 108(8): 1167-74.
[http://dx.doi.org/10.1172/JCI13505] [PMID: 11602624]
[151]
El-Mir MY, Nogueira V, Fontaine E, Avéret N, Rigoulet M, Leverve X. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem 2000; 275(1): 223-8.
[http://dx.doi.org/10.1074/jbc.275.1.223] [PMID: 10617608]
[152]
Hawley SA, Ross FA, Chevtzoff C, et al. Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab 2010; 11(6): 554-65.
[http://dx.doi.org/10.1016/j.cmet.2010.04.001] [PMID: 20519126]
[153]
Miller RA, Chu Q, Xie J, Foretz M, Viollet B, Birnbaum MJ. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature 2013; 494(7436): 256-60.
[http://dx.doi.org/10.1038/nature11808] [PMID: 23292513]
[154]
Fullerton MD, Galic S, Marcinko K, et al. Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat Med 2013; 19(12): 1649-54.
[http://dx.doi.org/10.1038/nm.3372] [PMID: 24185692]
[155]
Johanns M, Lai YC, Hsu MF, et al. AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B. Nat Commun 2016; 7: 10856.
[http://dx.doi.org/10.1038/ncomms10856] [PMID: 26952277]
[156]
He L, Sabet A, Djedjos S, et al. Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell 2009; 137(4): 635-46.
[http://dx.doi.org/10.1016/j.cell.2009.03.016] [PMID: 19450513]
[157]
Aatsinki SM, Buler M, Salomäki H, Koulu M, Pavek P, Hakkola J. Metformin induces PGC-1α expression and selectively affects hepatic PGC-1α functions. Br J Pharmacol 2014; 171(9): 2351-63.
[http://dx.doi.org/10.1111/bph.12585] [PMID: 24428821]
[158]
Tang J, Feng Y, Tsao S, Wang N, Curtain R, Wang Y. Berberine and Coptidis rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations. J Ethnopharmacol 2009; 126(1): 5-17.
[http://dx.doi.org/10.1016/j.jep.2009.08.009] [PMID: 19686830]
[159]
Grycová L, Dostál J, Marek R. Quaternary protoberberine alkaloids. Phytochemistry 2007; 68(2): 150-75.
[http://dx.doi.org/10.1016/j.phytochem.2006.10.004] [PMID: 17109902]
[160]
Jin Y, Khadka DB, Cho WJ. Pharmacological effects of berberine and its derivatives: a patent update. Expert Opin Ther Pat 2016; 26(2): 229-43.
[http://dx.doi.org/10.1517/13543776.2016.1118060] [PMID: 26610159]
[161]
Shao W, Espenshade PJ. Expanding roles for SREBP in metabolism. Cell Metab 2012; 16(4): 414-9.
[http://dx.doi.org/10.1016/j.cmet.2012.09.002] [PMID: 23000402]
[162]
Yu M, Alimujiang M, Hu L, Liu F, Bao Y, Yin J. Berberine alleviates lipid metabolism disorders via inhibition of mitochondrial complex I in gut and liver. Int J Biol Sci 2021; 17(7): 1693-707.
[http://dx.doi.org/10.7150/ijbs.54604] [PMID: 33994854]
[163]
Zheng J, Ramirez VD. Inhibition of mitochondrial proton F0F1-ATPase/ATP synthase by polyphenolic phytochemicals. Br J Pharmacol 2000; 130(5): 1115-23.
[http://dx.doi.org/10.1038/sj.bjp.0703397] [PMID: 10882397]
[164]
Li S, Bouzar C, Cottet-Rousselle C, et al. Resveratrol inhibits lipogenesis of 3T3-L1 and SGBS cells by inhibition of insulin signaling and mitochondrial mass increase. Biochim Biophys Acta 2016; 1857(6): 643-52.
[http://dx.doi.org/10.1016/j.bbabio.2016.03.009] [PMID: 26968895]
[165]
Sun X, Cao Z, Ma Y, et al. Resveratrol attenuates dapagliflozin-induced renal gluconeogenesis via activating the PI3K/Akt pathway and suppressing the FoxO1 pathway in type 2 diabetes. Food Funct 2021; 12(3): 1207-18.
[http://dx.doi.org/10.1039/D0FO02387F] [PMID: 33432947]
[166]
Kang OH, Kim SB, Seo YS, et al. Curcumin decreases oleic acid-induced lipid accumulation via AMPK phosphorylation in hepatocarcinoma cells. Eur Rev Med Pharmacol Sci 2013; 17(19): 2578-86.
[PMID: 24142602]
[167]
Kim T, Davis J, Zhang AJ, He X, Mathews ST. Curcumin activates AMPK and suppresses gluconeogenic gene expression in hepatoma cells. Biochem Biophys Res Commun 2009; 388(2): 377-82.
[http://dx.doi.org/10.1016/j.bbrc.2009.08.018] [PMID: 19665995]
[168]
Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE. Team T.-T. D. S. The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann Intern Med 2010; 152(6): 346-57.
[http://dx.doi.org/10.7326/0003-4819-152-6-201003160-00004] [PMID: 20231565]
[169]
Tuomi T, Honkanen EH, Isomaa B, Sarelin L, Groop LC. Improved prandial glucose control with lower risk of hypoglycemia with nateglinide than with glibenclamide in patients with maturity-onset diabetes of the young type 3. Diabetes Care 2006; 29(2): 189-94.
[http://dx.doi.org/10.2337/diacare.29.02.06.dc05-1314] [PMID: 16443858]
[170]
Quan HY, Kim SJ, Kim DY, Jo HK, Kim GW, Chung SH. Licochalcone A regulates hepatic lipid metabolism through activation of AMP-activated protein kinase. Fitoterapia 2013; 86: 208-16.
[http://dx.doi.org/10.1016/j.fitote.2013.03.005] [PMID: 23500383]
[171]
Lian Z, Li Y, Gao J, et al. A novel AMPK activator, WS070117, improves lipid metabolism discords in hamsters and HepG2 cells. Lipids Health Dis 2011; 10: 67.
[http://dx.doi.org/10.1186/1476-511X-10-67] [PMID: 21529359]