A NEW LOOK AT THE EFFECTS OF METFORMIN


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

One of the greatest achievements of the modern world is the increased duration of human life. However, this becomes a serious problem: as more people survive to old age, they are more likely to encounter diseases of old age, including diabetes mellitus type 2, cardiovascular diseases and cancer. Developing new ways of improving health in old age, therefore, is a priority for biomedical research. Still there is a lack of new and effective treatments. One of the current alternative strategies for the development of medicines is becoming repurposing of existing drugs for treatment of other diseases. Metformin is one of these drugs, which are being explored new points of application. Retrospective epidemiological studies indicate a possible association between metformin and decreased cancer risk, as confirmed in animal studies in vitro. Also special attention is currently given to the key role of microbiota in regulating age-associated diseases and the potential role of metformin in modulating its function. These data should provide the impetus to conduct randomized controlled trials to confirm or refute these additional benefits of metformin.

Full Text

Restricted Access

About the authors

Irina Vladimirovna Poluboyarinova

I.M. Sechenov First Moscow State Medical University

Email: polub-irina@mail.ru

Valentin Viktorovich Fadeev

I.M. Sechenov First Moscow State Medical University

Email: walfad@mail.ru

References

  1. Bailey C., Day C. Metformin: its botanical background. Pract. Diabetes Int. 2004;21:115-7.
  2. Watanabe C.K. Studies in the metabolic changes induced by administration of guanidine bases. I. Influence of injected guanidine hydrochloride upon blood sugar content. J. Biol. Chem. 1918;33:253-65.
  3. Nattrass M., Alberti K.G. Biguanides. Diabetologia. 1978;14(2):71-4.
  4. World Health Organization. WHO Model List of Essential Medicines, World Health Organization, Geneva, 2013.
  5. Morrish N.J., Wang S.L., Stevens L.K., Fuller J.H., Keen H. Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia. 2001;44 (Suppl 2):S14-S21.
  6. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-65.
  7. Holman R.R., Paul S.K., Bethel M.A., Matthews D.R., Neil H.A. 10-year follow-up of intensive glucose control in type 2 diabetes. N. Engl. J. Med. 2008;359:1577-89.
  8. Bhatt M.P., Lim Y.C., Kim Y.M., Ha K.S. C-peptide activates AMPK alpha and prevents ROS-mediated mitochondrial fission and endothelial apoptosis in diabetes. Diabetes. 2013;62:3851-62.
  9. Anfosso F., Chomiki N., Alessi M.C., Vague P., Juhan-Vague I. Plasminogen activator inhibitor-1 synthesis in the human hepatoma cell line HepG2. Metformin inhibits the stimulating effect of insulin. J. Clin. Invest.1993;91:2185-93.
  10. He G., Pedersen S.B., Bruun J.M., Lihn A.S., Richelsen B. Metformin, but not thiazolidinediones, inhibits plasminogen activator inhibitor-1 production in human adipose tissue in vitro. Horm. Metab. Res. 2003:35;18-23.
  11. Gin H., Freyburger G., Boisseau M., Aubertin J. Study of the effect of metformin on platelet aggregation in insulindependent diabetics. Diabetes Res. Clin. Pract. 1989:6;61-7.
  12. Boudina S., Abel E.D. Diabetic cardiomyopathy revisited. Circulation. 2007;115:3213-23.
  13. Ren J., Dominguez L.J., Sowers J.R., Davidoff A.J. Metformin but not glyburide prevents high glucose-induced abnormalities in relaxation and intracellular Ca2* transients in adult rat ventricular myocytes. Diabetes. 1999;48:2059-65.
  14. He C., Zhu H., Li H., Zou M.H., Xie Z. Dissociation of Bcl-2-Beclin1 complex by activated AMPK enhances cardiac autophagy and protects against cardiomyocyte apoptosis in diabetes. Diabetes. 2013;62:1270-81.
  15. Paiva M.A., Rutter-Locher Z., Goncalves L.M., Providencia L.A., Davidson S.M., Yellon D.M., Mocanu M.M. Enhancing AMPK activation during ischemia protects the diabetic heart against reperfusion injury. Am. J. Phys. Heart Circ. Physiol. 2011:300;H2123-H2134.
  16. Evans J.M., Donnelly L.A., Emslie-Smith A.M., Alessi D.R., Morris A.D. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005;330:1304-5.
  17. Franciosi M., Lucisano G., Lapice E., Strippoli G.F.M., Pellegrini F., Nicolucci A. Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review. PLoSOne. 2013;8:1-12.
  18. Pollak M. Insulin and insulin-like growth factor signaling in neoplasia. Nat. Rev. Cancer. 2008:8;915-28.
  19. Moiseeva O., Deschenes-Simard X., St-Germain E., Igelmann S., Huot G., Cadar A.E., Bourdeau V., Pollak M.N., Ferbeyre G. Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-kB activation. Aging Cell. 2013;12:489-98.
  20. Eikawa S., Nishida M., Mizukami S., Yamazaki C., Nakayama E., Udono H. Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc. Natl. Acad. Sci. USA. 2015;112:1809-14.
  21. Bowker S.L., Majumdar S.R., Veugelers P., Johnson J.A. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. 2006;29:254-8.
  22. Landman G.W., Kleefstra N., van Hateren K.J., Groenier K.H., Gans R.O., Bilo H.J. Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care. 2010;33:322-6.
  23. Hosono K., Endo H., Takahashi H., Sugiyama M., Sakai E., Uchiyama T., Suzuki K., Iida H., Sakamoto Y., Yoneda K., Koide T., Tokoro C., Abe Y., Inamori M., Nakagama H., Nakajima A. Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trial. Cancer Prev. Res (Phila). 2010;3:1077-83.
  24. Cabreiro F., Gems D. Treating aging: progress toward dietary restriction mimetics. F1000 Biol. Rep. 2010;2:76.
  25. Lepez-Otin C., Blasco M.A., Partridge L., Serrano M. and Kroemer G. (2013) The Hallmarks of aging. Cell. 2013;153:1194-1217.
  26. Mair W., Dillin A. Aging and survival: the genetics of lifespan extension by dietary restriction. Annu. Rev. Biochem. 2008;77:727-54.
  27. Masoro E.J., Yu B.P., Bertrand H.A. Action of food restriction in delaying the aging process. Proc. Natl. Acad. Sci. USA. 1982;79:4239-41.
  28. Walker G., Houthoofd K., Vanfleteren J.R., Gems D. Dietary restriction in C. elegans: from rate-of-living effects to nutrient sensing pathways. Mech. Ageing Dev. 2005;126:929-37.
  29. Ingram D.K., Anson R.M., deCabo R., Mamczarz J., Zhu M., Mattison J., Lane M.A., Roth G.S. Development of calorie restriction mimetics as a prolongevity strategy. Ann. N. Y. Acad. Sci. 2004;1019:412-23.
  30. Martin-Montalvo A., Mercken E.M., Mitchell S.J., Palacios H.H., Mote P.L., Scheibye-Knudsen M., Gomes A.P., Ward T.M., Minor R.K., Blouin M.J. et al. Metformin improves health span and lifespan in mice. Nat. Commun. 2013;4:2192.
  31. Stevens R.J., Ali R., Bankhead C.R., Bethel M.A., Cairns B.J., Camisasca R.P., Crowe F.L., Farmer A.J., Harrison S., Hirst J.A. et al. Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomized clinical trials. Diabetologia. 2012;55:2593-2603.
  32. Rosenberg E., Zilber-Rosenberg I. Symbiosis and development: the hologenome concept. Birth Defects Res. CEmbryo Today. 201 1:93;56-66.
  33. O'Hara A.M., Shanahan F. The gut flora as a forgotten organ. EMBORep. 2006:7;688-93.
  34. Cho I., Blaser M.J. The human microbiome: at the interface of healt hand disease. Nat. Rev. Genet. 2012:13;260-70.
  35. Claesson M.J., Jeffery I.B., Conde S., Power S.E., O'Connor E.M., Cusack S., Harris H.M., Coakley M., Lakshminarayanan B., O'Sullivan O. et al. (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012:488;178-84.
  36. Bailey C.J., Wilcock C., Scarpello J.H. Metformin and the intestine. Diabetologia. 2008;51:1552-53.
  37. Karlsson F.H., Tremaroli V., Nookaew I., Bergstrom G., Behre C.J., Fagerberg B., Nielsen J., Backhed F. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013;498:99-103.
  38. Maida A., Lamont B.J., Cao X. and Drucker D.J. Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-alpha in mice. Diabetologia. 2011;54:339-49.
  39. Sahin M., Tutuncu N.B., Ertugrul D., Tanaci N., Guvener N.D. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J. Diabetes Complications. 2007;21:118-23.
  40. Napolitano A., Miller S., Nicholls A.W., Baker D., VanHorn S., Thomas E., Rajpal D., Spivak A., Brown J.R., Nunez D.J. Novel gut-based pharmacology of metformin in patients with type 2 diabetes mellitus. PLoSOne. 2014;9:e100778.
  41. Nicholson J.K., Holmes E., Kinross J., Burcelin R., Gibson G., Jia W. and Pettersson S. Host-gut microbiota metabolic interactions. Science. 2012;336:1262-7.
  42. Islam K.B., Fukiya S., Hagio M., Fujii N., Ishizuka S., Ooka T., Ogura Y., Hayashi T. and Yokota A. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011;141:1773-81.
  43. Sum C.F., Webster J.M., Johnson A.B., Catalano C., Cooper B.G. and Taylor R. The effect of intravenous metformin on glucose metabolism during hyperglycaemia in type 2 diabetes. Diabet. Med. 1992;9:61-5.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2016 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies