Two Weeks of Metformin Treatment Enhances Mitochondrial Respiration in Skeletal Muscle of AMPK Kinase Dead but Not Wild Type Mice

PLoS ONE

Volumn 8, Issue 1, 2013, Pages

  Kristensen, Jonas M ^a,c   Larsen, Steen ^b   Helge, Jørn W ^b   Dela, Flemming ^b   Wojtaszewski, Jørgen F P ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXYACYL COENZYME A DEHYDROGENASE; CITRATE SYNTHASE; CYTOCHROME C; CYTOCHROME C OXIDASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; METFORMIN; MUSCLE SPECIFIC KINASE DEAD ALPHA 2; PYRUVATE DEHYDROGENASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); SUCCINATE DEHYDROGENASE (UBIQUINONE); UBIQUINOL CYTOCHROME C REDUCTASE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CARBOHYDRATE METABOLISM; CONTROLLED STUDY; ENZYME ACTIVITY; FEMALE; IN VIVO STUDY; LIPID METABOLISM; MITOCHONDRIAL RESPIRATION; MITOCHONDRION; MOUSE; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; TIBIALIS ANTERIOR MUSCLE; TREATMENT DURATION; TREATMENT RESPONSE;

3-HYDROXYACYL COA DEHYDROGENASES; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; BLOTTING, WESTERN; CELL RESPIRATION; CITRATE (SI)-SYNTHASE; CYTOCHROMES C; ELECTRON TRANSPORT; FEMALE; METFORMIN; MICE; MICE, INBRED C57BL; MITOCHONDRIA; MITOCHONDRIAL PROTEINS; MUSCLE, SKELETAL; PHOSPHORYLATION; PHOSPHOSERINE; PYRUVATE DEHYDROGENASE COMPLEX; SUBSTRATE SPECIFICITY;

MUS;

EID: 84872311894     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0053533     Document Type: Article

References (78)

1. Halimi S, (2006) Metformin: 50 years old, fit as a fiddle, and indispensable for its pivotal role in type 2 diabetes management. Diabetes Metab 32: 555-556 S1262-3636(07)70309-9 [pii];10.1016/S1262-3636(07)70309-9 [doi].
2. Stumvoll M, Haring HU, Matthaei S, (2007) Metformin. Endocr Res 32: 39-57.
3. Lowell BB, Shulman GI, (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307: 384-387 307/5708/384 [pii];10.1126/science.1104343 [doi].
4. Moreira PI, Oliveira CR, (2011) Mitochondria as potential targets in antidiabetic therapy. Handb Exp Pharmacol pp. 331-356 10.1007/978-3-642-17214-4_14 [doi].
5. Shulman GI, (2000) Cellular mechanisms of insulin resistance. J Clin Invest 106: 171-176 10.1172/JCI10583 [doi].
6. Boushel R, Gnaiger E, Schjerling P, Skovbro M, Kraunsoe R, et al. (2007) Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia 50: 790-796 10.1007/s00125-007-0594-3 [doi].
7. Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Andersen JL, et al. (2011) Increased mitochondrial substrate sensitivity in skeletal muscle of patients with type 2 diabetes. Diabetologia 10.1007/s00125-011-2098-4 [doi].
8. Hancock CR, Han DH, Chen M, Terada S, Yasuda T, et al. (2008) High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc Natl Acad Sci U S A 105: 7815-7820 0802057105 [pii];10.1073/pnas.0802057105 [doi].
9. Irving BA, Short KR, Nair KS, Stump CS, (2011) Nine days of intensive exercise training improves mitochondrial function but not insulin action in adult offspring of mothers with type 2 diabetes. J Clin Endocrinol Metab 96: E1137-E1141 jc.2010-2863 [pii];10.1210/jc.2010-2863 [doi].
10. Holloszy JO, (2009) Skeletal muscle "mitochondrial deficiency" does not mediate insulin resistance. Am J Clin Nutr 89: 463S-466S ajcn.2008.26717C [pii];10.3945/ajcn.2008.26717C [doi].
11. El Mir MY, Nogueira V, Fontaine E, Averet N, Rigoulet M, et al. (2000) Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem 275: 223-228.
12. Owen MR, Doran E, Halestrap AP, (2000) Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 348 Pt 3: 607-614.
13. Brunmair B, Staniek K, Gras F, Scharf N, Althaym A, et al. (2004) Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions? Diabetes 53: 1052-1059.
14. Carvalho C, Correia S, Santos MS, Seica R, Oliveira CR, et al. (2008) Metformin promotes isolated rat liver mitochondria impairment. Mol Cell Biochem 308: 75-83.
15. Turner N, Li JY, Gosby A, To SW, Cheng Z, et al. (2008) 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. Diabetes 57: 1414-1418.
16. Larsen S, Rabol R, Hansen CN, Madsbad S, Helge JW, et al. (2011) Metformin-treated patients with type 2 diabetes have normal mitochondrial complex I respiration. Diabetologia 10.1007/s00125-011-2340-0 [doi].
17. Kane DA, Anderson EJ, Price JW III, Woodlief TL, Lin CT, et al. (2010) Metformin selectively attenuates mitochondrial H2O2 emission without affecting respiratory capacity in skeletal muscle of obese rats. Free Radic Biol Med 49: 1082-1087 S0891-5849(10)00387-4 [pii];10.1016/j.freeradbiomed.2010.06.022 [doi].
18. Zhou G, Myers R, Li Y, Chen Y, Shen X, et al. (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108: 1167-1174.
19. Bikman BT, Zheng D, Kane DA, Anderson EJ, Woodlief TL, et al. (2010) Metformin Improves Insulin Signaling in Obese Rats via Reduced IKKbeta Action in a Fiber-Type Specific Manner. J Obes 201010.1155/2010/970865 [doi].
20. Suwa M, Egashira T, Nakano H, Sasaki H, Kumagai S, (2006) Metformin increases the PGC-1{alpha} protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo. J Appl Physiol.
21. Musi N, Hirshman MF, Nygren J, Svanfeldt M, Bavenholm P, et al. (2002) Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 51: 2074-2081.
22. Luna V, Casauban L, Sajan MP, Gomez-Daspet J, Powe JL, et al. (2006) Metformin improves atypical protein kinase C activation by insulin and phosphatidylinositol-3,4,5-(PO4)3 in muscle of diabetic subjects. Diabetologia 49: 375-382.
23. Hardie DG, Carling D, (1997) The AMP-activated protein kinase-fuel gauge of the mammalian cell? Eur J Biochem 246: 259-273.
24. Towler MC, Hardie DG, (2007) AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling. Circ Res 100: 328-341.
25. Bland ML, Birnbaum MJ, (2011) Cell biology. ADaPting to energetic stress. Science 332: 1387-1388 332/6036/1387 [pii];10.1126/science.1208444 [doi].
26. Hawley SA, Gadalla AE, Olsen GS, Hardie DG, (2002) The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes 51: 2420-2425.
27. Hardie DG, (2006) Neither LKB1 Nor AMPK Are the Direct Targets of Metformin. Gastroenterology 131: 973.
28. Zhang L, He H, Balschi JA, (2007) Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration. Am J Physiol Heart Circ Physiol.
29. Fryer LG, Parbu-Patel A, Carling D, (2002) The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem 277: 25226-25232.
30. Winder WW, Holmes BF, Rubink DS, Jensen EB, Chen M, et al. (2000) Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle. J Appl Physiol 88: 2219-2226.
31. Jorgensen SB, Treebak JT, Viollet B, Schjerling P, Vaulont S, et al. (2006) Role of {alpha}2-AMPK in basal, training- and AICAR-induced GLUT4, hexokinase II and mitochondrial protein expression in mouse muscle. Am J Physiol Endocrinol Metab.
32. Garcia-Roves PM, Osler ME, Holmstrom MH, Zierath JR, (2008) Gain-of-function R225Q mutation in AMP-activated protein kinase gamma3 subunit increases mitochondrial biogenesis in glycolytic skeletal muscle. J Biol Chem 283: 35724-35734 M805078200 [pii];10.1074/jbc.M805078200 [doi].
33. Leick L, Fentz J, Bienso RS, Knudsen JG, Jeppesen J, et al. (2010) PGC-1{alpha} is required for AICAR-induced expression of GLUT4 and mitochondrial proteins in mouse skeletal muscle. Am J Physiol Endocrinol Metab 299: E456-E465 ajpendo.00648.2009 [pii];10.1152/ajpendo.00648.2009 [doi].
34. O'Neill HM, Maarbjerg SJ, Crane JD, Jeppesen J, Jorgensen SB, et al. (2011) AMP-activated protein kinase (AMPK) {beta}1{beta}2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. Proc Natl Acad Sci U S A 1105062108 [pii];10.1073/pnas.1105062108 [doi].
35. Hou X, Song J, Li XN, Zhang L, Wang X, et al. (2010) Metformin reduces intracellular reactive oxygen species levels by upregulating expression of the antioxidant thioredoxin via the AMPK-FOXO3 pathway. Biochem Biophys Res Commun 396: 199-205 S0006-291X(10)00679-0 [pii];10.1016/j.bbrc.2010.04.017 [doi].
36. Batandier C, Guigas B, Detaille D, El-Mir MY, Fontaine E, et al. (2006) The ROS production induced by a reverse-electron flux at respiratory-chain complex 1 is hampered by metformin. J Bioenerg Biomembr 38: 33-42 10.1007/s10863-006-9003-8 [doi].
37. Kukidome D, Nishikawa T, Sonoda K, Imoto K, Fujisawa K, et al. (2006) Activation of AMP-Activated Protein Kinase Reduces Hyperglycemia-Induced Mitochondrial Reactive Oxygen Species Production and Promotes Mitochondrial Biogenesis in Human Umbilical Vein Endothelial Cells. Diabetes 55: 120-127.
38. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, et al. (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98: 115-124 S0092-8674(00)80611-X [pii];10.1016/S0092-8674(00)80611-X [doi].
39. Al-Khalili L, Forsgren M, Kannisto K, Zierath JR, Lonnqvist F, et al. (2005) Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1. Diabetologia 48: 1173-1179 10.1007/s00125-005-1741-3 [doi].
40. Jager S, Handschin C, St Pierre J, Spiegelman BM, (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A 104: 12017-12022.
41. Mu J, Brozinick JT Jr, Valladares O, Bucan M, Birnbaum MJ, (2001) A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle. Mol Cell 7: 1085-1094.
42. Pilegaard H, Birk JB, Sacchetti M, Mourtzakis M, Hardie DG, et al. (2006) PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise: effect of intralipid infusion. Diabetes 55: 3020-3027 55/11/3020 [pii];10.2337/db06-0152 [doi].
43. Woods A, Salt I, Scott J, Hardie DG, Carling D, (1996) The alpha1 and alpha2 isoforms of the AMP-activated protein kinase have similar activities in rat liver but exhibit differences in substrate specificity in vitro. FEBS Lett 397: 347-351.
44. Jorgensen SB, Treebak JT, Viollet B, Schjerling P, Vaulont S, et al. (2007) Role of AMPKalpha2 in basal, training-, and AICAR-induced GLUT4, hexokinase II, and mitochondrial protein expression in mouse muscle. Am J Physiol Endocrinol Metab 292: E331-E339 00243.2006 [pii];10.1152/ajpendo.00243.2006 [doi].
45. Holness MJ, Sugden MC, (2003) Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation. Biochem Soc Trans 31: 1143-1151.
46. Bailey CJ, Puah JA, (1986) Effect of metformin on glucose metabolism in mouse soleus muscle. Diabete Metab 12: 212-218.
47. Borst SE, Snellen HG, Lai HL, (2000) Metformin treatment enhances insulin-stimulated glucose transport in skeletal muscle of Sprague-Dawley rats. Life Sci 67: 165-174 S0024320500006123 [pii].
48. Borst SE, Snellen HG, (2001) Metformin, but not exercise training, increases insulin responsiveness in skeletal muscle of Sprague-Dawley rats. Life Sci 69: 1497-1507 S0024320501012255 [pii].
49. Penicaud L, Hitier Y, Ferre P, Girard J, (1989) Hypoglycaemic effect of metformin in genetically obese (fa/fa) rats results from an increased utilization of blood glucose by intestine. Biochem J 262: 881-885.
50. Cusi K, DeFronzo RA, (1998) Metformin: a review of its metabolic effects. Diabetes Reviews 6: 89-131.
51. Graham GG, Punt J, Arora M, Day RO, Doogue MP, et al. (2011) Clinical pharmacokinetics of metformin. Clin Pharmacokinet 50: 81-98 2 [pii];10.2165/11534750-000000000-00000 [doi].
52. Stephenne X, Foretz M, Taleux N, van der Zon GC, Sokal E, et al. (2011) Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status. Diabetologia 10.1007/s00125-011-2311-5 [doi].
53. Holloszy JO, (2008) Regulation by exercise of skeletal muscle content of mitochondria and GLUT4. J Physiol Pharmacol 59 Suppl 7: 5-18.
54. Joseph AM, Pilegaard H, Litvintsev A, Leick L, Hood DA, (2006) Control of gene expression and mitochondrial biogenesis in the muscular adaptation to endurance exercise. Essays Biochem 42: 13-29 bse0420013 [pii];10.1042/bse0420013 [doi].
55. Klein DK, Pilegaard H, Treebak JT, Jensen TE, Viollet B, et al. (2007) Lack of AMPKalpha2 enhances pyruvate dehydrogenase activity during exercise. Am J Physiol Endocrinol Metab 293: E1242-E1249.
56. Thomson DM, Hancock CR, Evanson BG, Kenney SG, Malan BB, et al. (2010) Skeletal muscle dysfunction in muscle-specific LKB1 knockout mice. J Appl Physiol 108: 1775-1785 japplphysiol.01293.2009 [pii];10.1152/japplphysiol.01293.2009 [doi].
57. Lee-Young RS, Griffee SR, Lynes SE, Bracy DP, Ayala JE, et al. (2009) Skeletal muscle AMP-activated protein kinase is essential for the metabolic response to exercise in vivo. J Biol Chem 284: 23925-23934 M109.021048 [pii];10.1074/jbc.M109.021048 [doi].
58. Jorgensen SB, Wojtaszewski JF, Viollet B, Andreelli F, Birk JB, et al. (2005) Effects of alpha-AMPK knockout on exercise-induced gene activation in mouse skeletal muscle. FASEB J 19: 1146-1148 04-3144fje [pii];10.1096/fj.04-3144fje [doi].
59. Foretz M, Hebrard S, Leclerc J, Zarrinpashneh E, Soty M, 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: 2355-2369 40671 [pii];10.1172/JCI40671 [doi].
60. Rabol R, Boushel R, Dela F, (2006) Mitochondrial oxidative function and type 2 diabetes. Appl Physiol Nutr Metab 31: 675-683 h06-071 [pii];10.1139/h06-071 [doi].
61. Sriwijitkamol A, Coletta DK, Wajcberg E, Balbontin GB, Reyna SM, et al. (2007) Effect of Acute Exercise on AMPK Signaling in Skeletal Muscle of Subjects With Type 2 Diabetes: A Time-Course and Dose-Response Study. Diabetes 56: 836-848.
62. Mortensen B, Poulsen P, Wegner L, Stender-Petersen KL, Ribel-Madsen R, et al. (2009) Genetic and metabolic effects on skeletal muscle AMPK in young and older twins. Am J Physiol Endocrinol Metab 297: E956-E964 00058.2009 [pii];10.1152/ajpendo.00058.2009 [doi].
63. Musi N, Fujii N, Hirshman MF, Ekberg I, Froberg S, et al. (2001) AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise. Diabetes 50: 921-927.
64. Hojlund K, Mustard KJ, Staehr P, Hardie DG, Beck-Nielsen H, et al. (2004) AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes. Am J Physiol Endocrinol Metab 286: E239-E244.
65. Wojtaszewski JFP, Birk JB, Frosig C, Holten M, Pilegaard H, et al. (2005) 5′AMP activated protein kinase expression in human skeletal muscle: effects of strength training and type 2 diabetes. J Physiol (Lond) 564: 563-573.
66. Aguer C, Mercier J, Man CY, Metz L, Bordenave S, et al. (2010) Intramyocellular lipid accumulation is associated with permanent relocation ex vivo and in vitro of fatty acid translocase (FAT)/CD36 in obese patients. Diabetologia 53: 1151-1163 10.1007/s00125-010-1708-x [doi].
67. Putman CT, Kiricsi M, Pearcey J, MacLean IM, Bamford JA, et al. (2003) AMPK activation increases uncoupling protein-3 expression and mitochondrial enzyme activities in rat muscle without fibre type transitions. J Physiol 551: 169-178.
68. Bergeron R, Ren JM, Cadman KS, Moore IK, Perret P, et al. (2001) Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis. Am J Physiol Endocrinol Metab 281: E1340-E1346.
69. Bamford JA, Lopaschuk GD, MacLean IM, Reinhart ML, Dixon WT, et al. (2003) Effects of chronic AICAR administration on the metabolic and contractile phenotypes of rat slow- and fast-twitch skeletal muscles. Can J Physiol Pharmacol 81: 1072-1082 10.1139/y03-110 [doi];y03-110 [pii].
70. Williams DB, Sutherland LN, Bomhof MR, Basaraba SA, Thrush AB, et al. (2009) Muscle-specific differences in the response of mitochondrial proteins to beta-GPA feeding: an evaluation of potential mechanisms. Am J Physiol Endocrinol Metab 296: E1400-E1408 90913.2008 [pii];10.1152/ajpendo.90913.2008 [doi].
71. Thomson DM, Porter BB, Tall JH, Kim HJ, Barrow JR, et al. (2007) Skeletal muscle and heart LKB1 deficiency causes decreased voluntary running and reduced muscle mitochondrial marker enzyme expression in mice. Am J Physiol Endocrinol Metab 292: E196-E202.
72. Brown JD, Hancock CR, Mongillo AD, Benjamin BJ, Digiovanni RA, et al. (2010) Effect of LKB1 deficiency on mitochondrial content, fibre type and muscle performance in the mouse diaphragm. Acta Physiol (Oxf) 10.1111/j.1748-1716.2010.02226.x [doi].
73. Rockl KS, Hirshman MF, Brandauer J, Fujii N, Witters LA, et al. (2007) Skeletal muscle adaptation to exercise training: AMP-activated protein kinase mediates muscle fiber type shift. Diabetes 56: 2062-2069 db07-0255 [pii];10.2337/db07-0255 [doi].
74. Zong H, Ren JM, Young LH, Pypaert M, Mu J, et al. (2002) AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A 99: 15983-15987.
75. Larsen S, Kristensen JM, Stride N, Wojtaszewski JF, Helge JW, et al. (2012) Skeletal muscle mitochondrial respiration in AMPKalpha2 kinase-dead mice. Acta Physiol (Oxf) 205: 314-320 10.1111/j.1748-1716.2011.02399.x [doi].
76. Dzamko N, Schertzer JD, Ryall JG, Steel R, Macaulay SL, et al. (2008) AMPK-independent pathways regulate skeletal muscle fatty acid oxidation. J Physiol 586: 5819-5831 jphysiol.2008.159814 [pii];10.1113/jphysiol.2008.159814 [doi].
77. Jensen TE, Rose AJ, Jorgensen SB, Brandt N, Schjerling P, et al. (2007) Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction. Am J Physiol Endocrinol Metab 292: E1308-E1317.
78. Maarbjerg SJ, Jorgensen SB, Rose AJ, Jeppesen J, Jensen TE, et al. (2009) Genetic impairment of AMPKalpha2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice. Am J Physiol Endocrinol Metab 297: E924-E934 90653.2008 [pii];10.1152/ajpendo.90653.2008 [doi].