Revisiting the mechanisms of metformin action in the liver

Annales d'Endocrinologie

Volumn 74, Issue 2, 2013, Pages 123-129

  Viollet, Benoit ^a,b   Foretz, Marc ^a,b  

^a INSTITUT COCHIN   (France)

^b UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE PHOSPHATE; ADENYLATE CYCLASE; CYCLIC AMP; GLUCAGON; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; HEMOGLOBIN A1C; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INCRETIN; METFORMIN; ORGANIC CATION TRANSPORTER 1; ORGANIC CATION TRANSPORTER 2; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PLACEBO; PROTEIN KINASE LKB1; PROTEIN SERINE THREONINE KINASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE);

ABDOMINAL PAIN; ANTIDIABETIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; CARDIOVASCULAR DISEASE; CELL ENERGY; DIARRHEA; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG STRUCTURE; ENERGY BALANCE; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; GENE EXPRESSION; GLUCONEOGENESIS; GLYCEMIC CONTROL; HUMAN; INHIBITION KINETICS; META ANALYSIS (TOPIC); MOLECULAR MECHANICS; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OVARY POLYCYSTIC DISEASE; PHARMACOGENETICS; PREGNANCY DIABETES MELLITUS; SIGNAL TRANSDUCTION; VOMITING;

EID: 84877626901     PISSN: 00034266     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ando.2013.03.006     Document Type: Article

References (55)

1. King H., Aubert R.E., Herman W.H. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 1998, 21:1414-1431.
2. Hurst R.T., Lee R.W. Increased incidence of coronary atherosclerosis in type 2 diabetes mellitus: mechanisms and management. Ann Intern Med 2003, 139:824-834.
3. Alberti K.G., Zimmet P.Z. New diagnostic criteria and classification of diabetes - again?. Diabet Med 1998, 15:535-536.
4. Saltiel A.R., Kahn C.R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001, 414:799-806.
5. Adler A.I., Shaw E.J., Stokes T., Ruiz F. Newer agents for blood glucose control in type 2 diabetes: summary of NICE guidance. BMJ 2009, 338:b1668.
6. Nathan D.M., Buse J.B., Davidson M.B., Ferrannini E., Holman R.R., Sherwin R., et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009, 32:193-203.
7. Turner R.C., Cull C.A., Frighi V., Holman R.R. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA: J Am Med Assoc 1999, 281:2005-2012.
8. UKPDS Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998, 352:854-865.
9. Gunton J.E., Delhanty P.J., Takahashi S., Baxter R.C. Metformin rapidly increases insulin receptor activation in human liver and signals preferentially through insulin-receptor substrate-2. J Clin Endocrinol Metab 2003, 88:1323-1332.
10. Mulherin A.J., Oh A.H., Kim H., Grieco A., Lauffer L.M., Brubaker P.L. Mechanisms underlying metformin-induced secretion of glucagon-like peptide-1 from the intestinal L cell. Endocrinology 2011, 152:4610-4619.
11. Maida A., Lamont B.J., Cao X., Drucker D.J. Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-alpha in mice. Diabetologia 2011, 54:339-349.
12. Lamanna C., Monami M., Marchionni N., Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2011, 13:221-228.
13. Selvin E., Bolen S., Yeh H.C., Wiley C., Wilson L.M., Marinopoulos S.S., et al. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med 2008, 168:2070-2080.
14. Correia S., Carvalho C., Santos M.S., Seica R., Oliveira C.R., Moreira P.I. Mechanisms of action of metformin in type 2 diabetes and associated complications: an overview. Mini Rev Med Chem 2008, 8:1343-1354.
15. Viollet B., Guigas B., Sanz Garcia N., Leclerc J., Foretz M., Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci 2012, 122:253-270.
16. Diamanti-Kandarakis E., Christakou C.D., Kandaraki E., Economou F.N. Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome. Eur J Endocrinol/Eur Fed Endoc Soc 2010, 162:193-212.
17. Scheen A.J. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 1996, 30:359-371.
18. Tucker G.T., Casey C., Phillips P.J., Connor H., Ward J.D., Woods H.F. Metformin kinetics in healthy subjects and in patients with diabetes mellitus. Brit J Clin Pharmacol 1981, 12:235-246.
19. Detaille D., Guigas B., Leverve X., Wiernsperger N., Devos P. Obligatory role of membrane events in the regulatory effect of metformin on the respiratory chain function. Biochem Pharmacol 2002, 63:1259-1272.
20. Shu Y., Sheardown S.A., Brown C., Owen R.P., Zhang S., Castro R.A., et al. Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest 2007, 117:1422-1431.
21. Zolk O. Disposition of metformin: variability due to polymorphisms of organic cation transporters. Ann Med 2012, 44:119-129.
22. Meyer F., Ipaktchi M., Clauser H. Specific inhibition of gluconeogenesis by biguanides. Nature 1967, 213:203-204.
23. 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. Diabetologia 2006, 49:434-441.
24. Zhou G., Myers R., Li Y., Chen Y., Shen X., Fenyk-Melody J., et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001, 108:1167-1174.
25. Viollet B., Guigas B., Leclerc J., Hebrard S., Lantier L., Mounier R., et al. AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives. Acta Physiol (Oxf) 2009, 196:81-98.
26. Hardie D.G., Ross F.A., Hawley S.A. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 2012, 13:251-262.
27. Carling D., Thornton C., Woods A., Sanders M.J. AMP-activated protein kinase: new regulation, new roles?. Biochem J 2012, 445:11-27.
28. Hawley S.A., Boudeau J., Reid J.L., Mustard K.J., Udd L., Makela T.P., 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, 2:28.
29. Shaw R.J., Kosmatka M., Bardeesy N., Hurley R.L., Witters L.A., DePinho R.A., et al. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci U S A 2004, 101:3329-3335.
30. Woods A., Johnstone S.R., Dickerson K., Leiper F.C., Fryer L.G., Neumann D., et al. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 2003, 13:2004-2008.
31. Hawley S.A., Pan D.A., Mustard K.J., Ross L., Bain J., Edelman A.M., et al. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab 2005, 2:9-19.
32. Woods A., Dickerson K., Heath R., Hong S.P., Momcilovic M., Johnstone S.R., et al. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab 2005, 2:21-33.
33. Hardie D.G. AMP-activated protein kinase as a drug target. Ann Rev Pharmacol Toxicol 2007, 47:185-210.
34. Hardie D.G. Neither LKB1 nor AMPK are the direct targets of metformin. Gastroenterology 2006, 131:973. author reply 974-5.
35. El-Mir M.Y., Nogueira V., Fontaine E., Averet N., Rigoulet M., Leverve X. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem 2000, 275:223-228.
36. Owen M.R., Doran E., Halestrap A.P. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 2000, 348(Pt 3):607-614.
37. Stephenne X., Foretz M., Taleux N., van der Zon G., Sokal E., Hue L., et al. Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status. Diabetologia 2011, 54:3101-3110.
38. Hawley S.A., Ross F.A., Chevtzoff C., Green K.A., Evans A., Fogarty S., et al. Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab 2010, 11:554-565.
39. Hinke S.A., Martens G.A., Cai Y., Finsi J., Heimberg H., Pipeleers D., et al. Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer. Br J Pharmacol 2007, 150:1031-1043.
40. Zou M.H., Kirkpatrick S.S., Davis B.J., Nelson J.S., Wiles WGt, Schlattner U., et al. Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo. Role of mitochondrial reactive nitrogen species. J Biol Chem 2004, 279:43940-43951.
41. Shaw R.J., Lamia K.A., Vasquez D., Koo S.H., Bardeesy N., Depinho R.A., et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 2005, 310:1642-1646.
42. Koo S.H., Flechner L., Qi L., Zhang X., Screaton R.A., Jeffries S., et al. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 2005, 437:1109-1111.
43. Caton P.W., Nayuni N.K., Kieswich J., Khan N.Q., Yaqoob M.M., Corder R. Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5. J Endocrinol 2010, 205:97-106.
44. Liu Y., Dentin R., Chen D., Hedrick S., Ravnskjaer K., Schenk S., et al. A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature 2008, 456:269-273.
45. He L., Sabet A., Djedjos S., Miller R., Sun X., Hussain M.A., et al. Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell 2009, 137:635-646.
46. Kim Y.D., Park K.G., Lee Y.S., Park Y.Y., Kim D.K., Nedumaran B., et al. Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP. Diabetes 2008, 57:306-314.
47. Lee J.M., Seo W.Y., Song K.H., Chanda D., Kim Y.D., Kim D.K., et al. AMPK-dependent repression of hepatic gluconeogenesis via disruption of CREB. CRTC2 complex by orphan nuclear receptor small heterodimer partner. J Biol Chem 2010, 285:32182-32191.
48. Foretz M., Hebrard S., Leclerc J., Zarrinpashneh E., Soty M., Mithieux G., et al. Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest 2010, 120:2355-2369.
49. Berglund E.D., Lee-Young R.S., Lustig D.G., Lynes S.E., Donahue E.P., Camacho R.C., et al. Hepatic energy state is regulated by glucagon receptor signaling in mice. J Clin Invest 2009, 119:2412-2422.
50. Miller R.A., Chu Q., Xie J., Foretz M., Viollet B., Birnbaum M.J. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature 2013, 494:256-260.
51. Wang Z.J., Yin O.Q., Tomlinson B., Chow M.S. OCT2 polymorphisms and in-vivo renal functional consequence: studies with metformin and cimetidine. Pharmacogenet Genomics 2008, 18:637-645.
52. Tzvetkov M.V., Vormfelde S.V., Balen D., Meineke I., Schmidt T., Sehrt D., et al. The effects of genetic polymorphisms in the organic cation transporters OCT1? OCT2, and OCT3 on the renal clearance of metformin. Clin Pharmacol Ther 2009, 86:299-306.
53. Zhou K., Bellenguez C., Spencer C.C., Bennett A.J., Coleman R.L., Tavendale R., et al. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet 2011, 43:117-120.
54. Woods A., Leiper J.M., Carling D. The role of ATM in response to metformin treatment and activation of AMPK. Nat Genet 2012, 44:360-361.
55. Yee S.W., Chen L., Giacomini K.M. The role of ATM in response to metformin treatment and activation of AMPK. Nat Genet 2012, 44:359-360.