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Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status.

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Stéphenne, Xavier [UCL] Foretz, M. Taleux, N. van der Zon, G.C. Sokal, Etienne [UCL] Guigas, B.

The glucose-lowering drug metformin has been shown to activate hepatic AMP-activated protein kinase (AMPK), a master kinase regulating cellular energy homeostasis. However, the underlying mechanisms remain controversial and have never been investigated in primary human hepatocytes.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2011
Language Anglais
Journal information "Diabetologia : clinical and experimental diabetes and metabolism" - Vol. 54, no. 12, p. 3101-3110 (2011)
Peer reviewed yes
Publisher Springer ((Germany) Heidelberg)
issn 0012-186X
e-issn 1432-0428
Publication status Publié
Affiliations UCL - SSS/IREC/PEDI - Pôle de Pédiatrie
UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique
UCL - (SLuc) Service de pédiatrie spécialisée
UCL - (SLuc) Centre de pathologie anorectale de l'enfant
MESH Subject Rats ; Oxygen Consumption - drug effects ; Mitochondria, Liver - drug effects - metabolism ; Mice, Knockout ; Mice ; Metformin - pharmacology ; Male ; Isoenzymes - metabolism ; Hypoglycemic Agents - pharmacology ; Humans ; Hepatocytes - drug effects - enzymology ; Cells, Cultured ; Animals ; Adenine Nucleotides - analysis ; AMP-Activated Protein Kinases - analysis - drug effects
Keywords Metformin ; Hepatocytes ; Liver cells
Links
  1. Goodarzi Mark O., Bryer-Ash Michael, Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents, 10.1111/j.1463-1326.2004.00448.x
  2. Nathan D. M., Buse J. B., Davidson M. B., Ferrannini E., Holman R. R., Sherwin R., Zinman B., Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy : A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes, 10.1007/s00125-008-1157-y
  3. Natali A., Ferrannini E., Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: a systematic review, 10.1007/s00125-006-0141-7
  4. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34), 10.1016/s0140-6736(98)07037-8
  5. Ben Sahra I., Le Marchand-Brustel Y., Tanti J.-F., Bost F., Metformin in Cancer Therapy: A New Perspective for an Old Antidiabetic Drug?, 10.1158/1535-7163.mct-09-1186
  6. Zhou Gaochao, Myers Robert, Li Ying, Chen Yuli, Shen Xiaolan, Fenyk-Melody Judy, Wu Margaret, Ventre John, Doebber Thomas, Fujii Nobuharu, Musi Nicolas, Hirshman Michael F., Goodyear Laurie J., Moller David E., Role of AMP-activated protein kinase in mechanism of metformin action, 10.1172/jci13505
  7. Shaw R. J., The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin, 10.1126/science.1120781
  8. Steinberg G. R., Kemp B. E., AMPK in Health and Disease, 10.1152/physrev.00011.2008
  9. Hardie D. Grahame, AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy, 10.1038/nrm2249
  10. Oakhill J. S., Steel R., Chen Z.-P., Scott J. W., Ling N., Tam S., Kemp B. E., AMPK Is a Direct Adenylate Charge-Regulated Protein Kinase, 10.1126/science.1200094
  11. Brunmair B., Staniek K., Gras F., Scharf N., Althaym A., Clara R., Roden M., Gnaiger E., Nohl H., Waldhausl W., Furnsinn C., Thiazolidinediones, Like Metformin, Inhibit Respiratory Complex I: A Common Mechanism Contributing to Their Antidiabetic Actions?, 10.2337/diabetes.53.4.1052
  12. El-Mir Mohamad-Yehia, Nogueira Véronique, Fontaine Eric, Avéret Nicole, Rigoulet Michel, Leverve Xavier, Dimethylbiguanide Inhibits Cell Respiration via an Indirect Effect Targeted on the Respiratory Chain Complex I, 10.1074/jbc.275.1.223
  13. OWEN Mark R., DORAN Elena, HALESTRAP Andrew P., Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain, 10.1042/0264-6021:3480607
  14. Fryer Lee G. D., Parbu-Patel Asha, Carling David, The Anti-diabetic Drugs Rosiglitazone and Metformin Stimulate AMP-activated Protein Kinase through Distinct Signaling Pathways, 10.1074/jbc.m202489200
  15. Hawley S. A., Gadalla A. E., Olsen G. S., Hardie D. G., The Antidiabetic Drug Metformin Activates the AMP-Activated Protein Kinase Cascade via an Adenine Nucleotide-Independent Mechanism, 10.2337/diabetes.51.8.2420
  16. Hardie David Grahame, Neither LKB1 Nor AMPK Are the Direct Targets of Metformin, 10.1053/j.gastro.2006.07.032
  17. Fujita Y., Hosokawa M., Fujimoto S., Mukai E., Abudukadier A., Obara A., Ogura M., Nakamura Y., Toyoda K., Nagashima K., Seino Y., Inagaki N., Metformin suppresses hepatic gluconeogenesis and lowers fasting blood glucose levels through reactive nitrogen species in mice, 10.1007/s00125-010-1729-5
  18. Guigas B., Bertrand L., Taleux N., Foretz M., Wiernsperger N., Vertommen D., Andreelli F., Viollet B., Hue L., 5-Aminoimidazole-4-Carboxamide-1- -D-Ribofuranoside and Metformin Inhibit Hepatic Glucose Phosphorylation by an AMP-Activated Protein Kinase-Independent Effect on Glucokinase Translocation, 10.2337/diabetes.55.04.06.db05-1178
  19. Berry M. N., HIGH-YIELD PREPARATION OF ISOLATED RAT LIVER PARENCHYMAL CELLS: A Biochemical and Fine Structural Study, 10.1083/jcb.43.3.506
  20. GROEN Albert K., SIPS Herman J., VERVOORN Richard C., TAGER Joseph M., Intracellular Compartment ation and Control of Alanine Metabolism in Rat Liver Parenchymal Cells, 10.1111/j.1432-1033.1982.tb05851.x
  21. Detaille D., Guigas B., Chauvin C., Batandier C., Fontaine E., Wiernsperger N., Leverve X., Metformin Prevents High-Glucose-Induced Endothelial Cell Death Through a Mitochondrial Permeability Transition-Dependent Process, 10.2337/diabetes.54.7.2179
  22. Detaille Dominique, Guigas Bruno, Leverve Xavier, Wiernsperger Nicolas, Devos Pierre, Obligatory role of membrane events in the regulatory effect of metformin on the respiratory chain function, 10.1016/s0006-2952(02)00858-4
  23. El-Mir Mohamad-Yehia, Detaille Dominique, R-Villanueva Gloria, Delgado-Esteban Maria, Guigas Bruno, Attia Stephane, Fontaine Eric, Almeida Angeles, Leverve Xavier, Neuroprotective Role of Antidiabetic Drug Metformin Against Apoptotic Cell Death in Primary Cortical Neurons, 10.1007/s12031-007-9002-1
  24. GUIGAS Bruno, DETAILLE Dominique, CHAUVIN Christiane, BATANDIER Cécile, De OLIVEIRA Frédéric, FONTAINE Eric, LEVERVE Xavier, Metformin inhibits mitochondrial permeability transition and cell death: a pharmacologicalin vitrostudy, 10.1042/bj20040885
  25. Batandier Cécile, Guigas Bruno, Detaille Dominique, El-Mir M., Fontaine Eric, Rigoulet M., Leverve X. M., The ROS Production Induced by a Reverse-Electron Flux at Respiratory-Chain Complex 1 is Hampered by Metformin, 10.1007/s10863-006-9003-8
  26. Hinke S A, Martens G A, Cai Y, Finsi J, Heimberg H, Pipeleers D, Casteele M, Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic β-cells through restoration of mitochondrial electron transfer : Methyl succinate and metformin in islet β-cells, 10.1038/sj.bjp.0707189
  27. Turner N., Li J.-Y., Gosby A., To S. W.C., Cheng Z., Miyoshi H., Taketo M. M., Cooney G. J., Kraegen E. W., James D. E., Hu L.-H., Li J., Ye J.-M., Berberine and Its More Biologically Available Derivative, Dihydroberberine, Inhibit Mitochondrial Respiratory Complex I: A Mechanism for the Action of Berberine to Activate AMP-Activated Protein Kinase and Improve Insulin Action, 10.2337/db07-1552
  28. Hawley Simon A., Ross Fiona A., Chevtzoff Cyrille, Green Kevin A., Evans Ashleigh, Fogarty Sarah, Towler Mhairi C., Brown Laura J., Ogunbayo Oluseye A., Evans A. Mark, Hardie D. Grahame, Use of Cells Expressing γ Subunit Variants to Identify Diverse Mechanisms of AMPK Activation, 10.1016/j.cmet.2010.04.001
  29. Zhang L., He H., Balschi J. A., Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration, 10.1152/ajpheart.00002.2007
  30. Guigas Bruno, Taleux Nellie, Foretz Marc, Detaille Dominique, Andreelli Fabrizio, Viollet Benoit, Hue Louis, AMP-activated protein kinase-independent inhibition of hepatic mitochondrial oxidative phosphorylation by AICA riboside, 10.1042/bj20070105
  31. Foretz Marc, Hébrard Sophie, Leclerc Jocelyne, Zarrinpashneh Elham, Soty Maud, Mithieux Gilles, Sakamoto Kei, Andreelli Fabrizio, Viollet Benoit, Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state, 10.1172/jci40671
  32. Papa Sergio, De Rasmo Domenico, Scacco Salvatore, Signorile Anna, Technikova-Dobrova Zuzana, Palmisano Giuseppe, Sardanelli Anna Maria, Papa Francesco, Panelli Damiano, Scaringi Raffaella, Santeramo Arcangela, Mammalian complex I: A regulable and vulnerable pacemaker in mitochondrial respiratory function, 10.1016/j.bbabio.2008.04.005
  33. Mahlapuu M., Expression profiling of the  -subunit isoforms of AMP-activated protein kinase suggests a major role for  3 in white skeletal muscle, 10.1152/ajpendo.00147.2003
  34. Wojtaszewski Jørgen F. P., Birk Jesper B., Frøsig Christian, Holten Mads, Pilegaard Henriette, Dela Flemming, 5′AMP activated protein kinase expression in human skeletal muscle: effects of strength training and type 2 diabetes : Diabetes, training and AMPK, 10.1113/jphysiol.2005.082669
  35. CHEUNG Peter C.F., SALT Ian P., DAVIES Stephen P., HARDIE D. Grahame, CARLING David, Characterization of AMP-activated protein kinase γ-subunit isoforms and their role in AMP binding, 10.1042/0264-6021:3460659
  36. Birk J. B., Wojtaszewski J. F. P., Predominant α2/β2/γ3 AMPK activation during exercise in human skeletal muscle : Differential AMPK trimer activation in muscle, 10.1113/jphysiol.2006.120972
  37. Treebak J. T., Glund S., Deshmukh A., Klein D. K., Long Y. C., Jensen T. E., Jorgensen S. B., Viollet B., Andersson L., Neumann D., Wallimann T., Richter E. A., Chibalin A. V., Zierath J. R., Wojtaszewski J. F.P., AMPK-Mediated AS160 Phosphorylation in Skeletal Muscle Is Dependent on AMPK Catalytic and Regulatory Subunits, 10.2337/db06-0175
  38. Quinn J. M. W., Tam S., Sims N. A., Saleh H., McGregor N. E., Poulton I. J., Scott J. W., Gillespie M. T., Kemp B. E., van Denderen B. J. W., Germline deletion of AMP-activated protein kinase   subunits reduces bone mass without altering osteoclast differentiation or function, 10.1096/fj.09-137158
  39. SALT Ian, CELLER Jakub W., HAWLEY Simon A., PRESCOTT Alan, WOODS Angela, CARLING David, HARDIE D. Grahame, AMP-activated protein kinase: greater AMP dependence, and preferential nuclear localization, of complexes containing the α2 isoform, 10.1042/bj3340177
  40. Kazgan N., Williams T., Forsberg L. J., Brenman J. E., Identification of a Nuclear Export Signal in the Catalytic Subunit of AMP-activated Protein Kinase, 10.1091/mbc.e10-04-0347
  41. Kodiha M., Rassi J. G., Brown C. M., Stochaj U., Localization of AMP kinase is regulated by stress, cell density, and signaling through the MEK->ERK1/2 pathway, 10.1152/ajpcell.00176.2007
  42. Suzuki A., Okamoto S., Lee S., Saito K., Shiuchi T., Minokoshi Y., Leptin Stimulates Fatty Acid Oxidation and Peroxisome Proliferator-Activated Receptor   Gene Expression in Mouse C2C12 Myoblasts by Changing the Subcellular Localization of the  2 Form of AMP-Activated Protein Kinase, 10.1128/mcb.02222-06
  43. Wilcock C., Bailey C. J., Accumulation of metformin by tissues of the normal and diabetic mouse, 10.3109/00498259409043220
  44. WILCOCK CAROL, WYRE N. D., BAILEY C. J., Subcellular distribution of metformin in rat liver, 10.1111/j.2042-7158.1991.tb03507.x
  45. Tucker GT, Measurement of the renal clearance of drugs., 10.1111/j.1365-2125.1981.tb01304.x
  46. Graham Garry G., Punt Jeroen, Arora Manit, Day Richard O., Doogue Matthew P., Duong Janna K., Furlong Timothy J., Greenfield Jerry R., Greenup Louise C., Kirkpatrick Carl M., Ray John E., Timmins Peter, Williams Kenneth M., Clinical Pharmacokinetics of Metformin : , 10.2165/11534750-000000000-00000
  47. Wang D.-S., Involvement of Organic Cation Transporter 1 in Hepatic and Intestinal Distribution of Metformin, 10.1124/jpet.102.034140
  48. Shu Yan, Sheardown Steven A., Brown Chaline, Owen Ryan P., Zhang Shuzhong, Castro Richard A., Ianculescu Alexandra G., Yue Lin, Lo Joan C., Burchard Esteban G., Brett Claire M., Giacomini Kathleen M., Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action, 10.1172/jci30558
  49. Jang Eun-Hee, Klm Hyoung-Kwang, Park Chang-Shin, Kang Ju-Hee, Increased Expression of Hepatic Organic Cation Transporter 1 and Hepatic Distribution of Metformin in High-fat Diet-induced Obese Mice, 10.2133/dmpk.dmpk-10-nt-010
Bibliographic reference Stéphenne, Xavier ; Foretz, M. ; Taleux, N. ; van der Zon, G.C. ; Sokal, Etienne ; et. al. Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status.. In: Diabetologia : clinical and experimental diabetes and metabolism, Vol. 54, no. 12, p. 3101-3110 (2011)
Permanent URL http://hdl.handle.net/2078.1/104984