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Research Article

Increased metformin dosage suppresses pro-inflammatory cytokine levels in systemic circulation and might contribute to its beneficial effects

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References

  • Domingueti, C. P.; Dusse, L. M.; Carvalho, M.; de Sousa, L. P.; Gomes, K. B.; Fernandes, A. P. Diabetes Mellitus: The Linkage between Oxidative Stress, Inflammation, Hypercoagulability and Vascular Complications. J. Diabet. Complicat. 2016, 30(4), 738–745. DOI: 10.1016/j.jdiacomp.2015.12.018.
  • Longo PL, Artese HP, Rabelo MS, Kawamoto D, Foz AM, Romito GA, et al. Serum Levels of Inflammatory Markers in Type 2 Diabetes Patients with Chronic Periodontitis. J. Appl. Oral Sci. 2014, 22(2), 103–108.
  • Schmidt MI, Duncan BB, Sharrett AR, Lindberg G, Savage PJ, Offenbacher S, et al.. Markers of Inflammation and Prediction of Diabetes Mellitus in Adults (Atherosclerosis Risk in Communities Study): A Cohort Study. Lancet (London, England). 1999, 353(9165), 1649–1652.
  • Danquah I, Bedu-Addo G, Terpe K-J, Micah F, Amoako YA, Awuku YA, et al. Diabetes Mellitus Type 2 in Urban Ghana: Characteristics and Associated Factors. BMC Public Health. 2012, 12(1), 210.
  • Woo SL, Xu H, Li H, Zhao Y, Hu X, Zhao J, et al.. Metformin Ameliorates Hepatic Steatosis and Inflammation without Altering Adipose Phenotype in Diet-induced Obesity. PloS One. 2014, 9(3), e91111.
  • Rena, G.; Pearson, E. R.; Sakamoto, K. Molecular Mechanism of Action of Metformin: Old or New Insights? Diabetologia. 2013, 56(9), 1898–1906. DOI: 10.1007/s00125-013-2991-0.
  • Rena, G.; Pearson, E. R.; Sakamoto, K. J. D. M. Molecular Action and Pharmacogenetics of Metformin: Current Understanding of an Old Drug. Diabetes Management. 2012, 2(5), 439–452. DOI: 10.1038/srep00439.
  • Viollet, B.; Guigas, B.; Sanz Garcia, N.; Leclerc, J.; Foretz, M.; Andreelli, F. Cellular and Molecular Mechanisms of Metformin: An Overview. Clinic. Sci. 2012, 122(6), 253–270. DOI: 10.1042/CS20110386.
  • Kim, S. A.; Choi, H. C. Metformin Inhibits Inflammatory Response via AMPK-PTEN Pathway in Vascular Smooth Muscle Cells. Biochem. Biophys. Res. Commun. 2012, 425, 866–872. DOI: 10.1016/j.bbrc.2012.07.165.
  • Koh, S. J.; Kim, J. M.; Kim, I. K.; Ko, S. H.; Kim, J. S. Antiinflammatory Mechanism of Metformin and Its Effects in Intestinal Inflammation and Colitisassociated Colon Cancer. J. Gastroenterol. Hepatol. 2014, 29, 502–510. DOI: 10.1111/jgh.12435.
  • Chen, W.; Liu, X.; Ye, S. Effects of Metformin on Blood and Urine Pro-inflammatory Mediators in Patients with Type 2 Diabetes. J. Inflammat. 2016, 13(1), 34. DOI: 10.1186/s12950-016-0142-3.
  • Brooks-Worrell, B.; Palmer, J. P. Immunology in the Clinic Review Series; Focus on Metabolic Diseases: Development of Islet Autoimmune Disease in Type 2 Diabetes Patients: Potential Sequelae of Chronic Inflammation. Clin. Exp. Immunol. 2012, 167(1), 40–46. DOI: 10.1111/j.1365-2249.2011.04501.x.
  • Eguchi, K.; Nagai, R. Islet Inflammation in Type 2 Diabetes and Physiology. J. Clin. Invest. 2017, 127(1), 14–23. DOI: 10.1172/JCI88877.
  • Hotamisligil, G. S.; Shargill, N. S.; Spiegelman, B. M. Adipose Expression of Tumor Necrosis Factor-alpha: Direct Role in Obesity-linked Insulin Resistance. Science (New York, NY). 1993, 259(5091), 87–91. DOI: 10.1126/science.7678183.
  • Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, et al. . Adipocyte Death Defines Macrophage Localization and Function in Adipose Tissue of Obese Mice and Humans. J. Lipid Res. 2005, 46(11), 2347–2355.
  • Goyal, R.; Faizy, A. F.; Siddiqui, S. S.; Singhai, M. Evaluation of TNF-alpha and IL-6 Levels in Obese and Non-obese Diabetics: Pre- and Postinsulin Effects. North Am. J. Med. Sci. 2012, 4(4), 180–184. DOI: 10.4103/1947-2714.94944.
  • Marques-Vidal P, Schmid R, Bochud M, Bastardot F, von Känel R, Paccaud F, et al. Adipocytokines, Hepatic and Inflammatory Biomarkers and Incidence of Type 2 Diabetes. The CoLaus Study. PloS One. 2012, 7(12), e51768.
  • Popko K, Gorska E, Stelmaszczyk-Emmel A, Plywaczewski R, Stoklosa A, Gorecka D, et al.  Proinflammatory Cytokines Il-6 and TNF-alpha and the Development of Inflammation in Obese Subjects. Eur. J. Med. Res. 2010, 15(Suppl 2), 120–122.
  • Shoelson, S. E.; Lee, J.; Goldfine, A. B. Inflammation and Insulin Resistance. J. Clin. Invest. 2006, 116(7), 1793–1801. DOI: 10.1172/JCI29069.
  • Weisberg, S. P.; McCann, D.; Desai, M.; Rosenbaum, M.; Leibel, R. L.; Ferrante, A. W., Jr. Obesity Is Associated with Macrophage Accumulation in Adipose Tissue. J. Clin. Invest. 2003, 112(12), 1796–1808. DOI: 10.1172/JCI200319246.
  • Al-Shukaili, A.; AL-Ghafri, S.; Al-Marhoobi, S.; Al-Abri, S.; Al-Lawati, J.; Al-Maskari, M. Analysis of Inflammatory Mediators in Type 2 Diabetes Patients. Int. J. Endocrinol. 2013, 2013, 7. DOI: 10.1155/2013/976810.
  • Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M, et al.. T-lymphocyte Infiltration in Visceral Adipose Tissue: A Primary Event in Adipose Tissue Inflammation and the Development of Obesity-mediated Insulin Resistance. Arterioscler. Thromb. Vasc. Biol. 2008, 28(7), 1304–1310.
  • Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, et al. CD8+ Effector T Cells Contribute to Macrophage Recruitment and Adipose Tissue Inflammation in Obesity. Nat. Med. 2009, 15(8), 914–920.
  • Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, et al. Normalization of Obesity-associated Insulin Resistance through Immunotherapy. Nat. Med. 2009, 15(8), 921–929.
  • .Wu H, Ghosh S, Perrard XD, Feng L, Garcia GE, Perrard JL, et al.  T-cell Accumulation and Regulated on Activation, Normal T Cell Expressed and Secreted Upregulation in Adipose Tissue in Obesity. Circulation. 2007, 115(8), 1029–1038.
  • Feve, B.; Bastard, J. P. The Role of Interleukins in Insulin Resistance and Type 2 Diabetes Mellitus. Nat. Rev. Endocrinol. 2009, 5(6), 305–311. DOI: 10.1038/nrendo.2009.62.
  • Hotamisligil, G. S.;. Inflammatory Pathways and Insulin Action. Int. J. Obes. Relate. Metabol. Disorder. 2003, 27(Suppl 3), S53–55.
  • Moller, D. E.;. Potential Role of TNF-alpha in the Pathogenesis of Insulin Resistance and Type 2 Diabetes. Trend. endocrinol. metabol. 2000, 11(6), 212–217. DOI: 10.1016/S1043-2760(00)00272-1.
  • Kim, J. H.; Bachmann, R. A.; Chen, J. Interleukin-6 and Insulin Resistance. Vitamin. hormon. 2009, 80, 613–633.
  • Senn, J. J.; Klover, P. J.; Nowak, I. A.; Mooney, R. A. Interleukin-6 Induces Cellular Insulin Resistance in Hepatocytes. Diabetes. 2002, 51(12), 3391–3399. DOI: 10.2337/diabetes.51.12.3391.
  • Spranger J, Kroke A, Mohlig M, Hoffmann K, Bergmann MM, Ristow M, et al. Inflammatory Cytokines and the Risk to Develop Type 2 Diabetes: Results of the Prospective Population-based European Prospective Investigation into Cancer and Nutrition (Epic)-potsdam Study. Diabetes. 2003, 52(3), 812–817.
  • Crook, M.;. Type 2 Diabetes Mellitus: A Disease of the Innate Immune System? an Update. Diabet. Med. 2004, 21(3), 203–207. DOI: 10.1046/j.1464-5491.2003.01030.x.
  • van Exel, E.; Gussekloo, J.; de Craen, A. J.; Frolich, M. Bootsma-Van Der Wiel A, Westendorp RG. Low Production Capacity of Interleukin-10 Associates with the Metabolic Syndrome and Type 2 Diabetes: The Leiden 85-Plus Study. Diabetes. 2002, 51(4), 1088–1092. DOI: 10.2337/diabetes.51.4.1088.
  • Kelchtermans, H.; Billiau, A.; Matthys, P. How Interferon-gamma Keeps Autoimmune Diseases in Check. Trends Immunol. 2008, 29(10), 479–486. DOI: 10.1016/j.it.2008.07.002.
  • Campbell, I. L.; Iscaro, A.; Harrison, L. C. IFN-gamma and Tumor Necrosis Factor-alpha. Cytotoxicity to Murine Islets of Langerhans. J. Immunol. 1988, 141(7), 2325–2329.
  • .Jagannathan-Bogdan M, McDonnell ME, Shin H, Rehman Q, Hasturk H, Apovian CM, et al. Elevated Proinflammatory Cytokine Production by a Skewed T Cell Compartment Requires Monocytes and Promotes Inflammation in Type 2 Diabetes. J. Immunol. 2011, 186(2), 1162–1172.
  • Sumarac-Dumanovic M, Jeremic D, Pantovic A, Janjetovic K, Stamenkovic-Pejkovic D, Cvijovic G, et al. Therapeutic Improvement of Glucoregulation in Newly Diagnosed Type 2 Diabetes Patients Is Associated with a Reduction of IL-17 Levels. Immunobiology. 2013, 218(8), 1113–1118.
  • Abdel-Moneim, A.; Bakery, H. H.; Allam, G. The Potential Pathogenic Role of IL-17/Th17 Cells in Both Type 1 and Type 2 Diabetes Mellitus. Biomed. Pharmacother. 2018, 101, 287–292. DOI: 10.1016/j.biopha.2018.02.103.
  • van Nieuwenhuijze, A.; Koenders, M.; Roeleveld, D.; Sleeman, M. A.; van den Berg, W.; Wicks, I. P. GM-CSF as a Therapeutic Target in Inflammatory Diseases. Mol. Immunol. 2013, 56(4), 675–682. DOI: 10.1016/j.molimm.2013.05.002.
  • Hamilton, J. A.; Anderson, G. P. Mini ReviewGM-CSF Biology. Growth Factors. 2004, 22(4), 225–231. DOI: 10.1080/08977190412331279881.
  • Robertson, R. P.; Harmon, J.; Tran, P. O.; Poitout, V. Beta-cell Glucose Toxicity, Lipotoxicity, and Chronic Oxidative Stress in Type 2 Diabetes. Diabetes. 2004, 53(Suppl 1), S119–124. DOI: 10.2337/diabetes.53.2007.S119.
  • Donath, M. Y.;. Targeting Inflammation in the Treatment of Type 2 Diabetes: Time to Start. Nat. Rev. Drug Discovery. 2014, 13(6), 465–476. DOI: 10.1038/nrd4275.
  • Donath, M. Y.; Shoelson, S. E. Type 2 Diabetes as an Inflammatory Disease. Nat. Rev. Immunol. 2011, 11(2), 98–107. DOI: 10.1038/nri2925.
  • Krysiak, R.; Okopien, B. Lymphocyte-suppressing and Systemic Anti-inflammatory Effects of High-dose Metformin in Simvastatin-treated Patients with Impaired Fasting Glucose. Atherosclerosis. 2012, 225(2), 403–407. DOI: 10.1016/j.atherosclerosis.2012.09.034.
  • Mo D, Liu S, Ma H, Tian H, Yu H, Zhang X, et al. Effects of Acarbose and Metformin on the Inflammatory State in Newly Diagnosed Type 2 Diabetes Patients: A One-year Randomized Clinical Study. Drug Des. Devel. Ther. 2019, 13, 2769–2776. DOI: 10.2147/DDDT.S208327.
  • Hyun B, Shin S, Lee A, Lee S, Song Y, Ha NJ, et al. Metformin Down-regulates TNF-alpha Secretion via Suppression of Scavenger Receptors in Macrophages. Immun. net. 2013, 13(4), 123–132.
  • Hamilton, J. A.;. GM-CSF as a Target in Inflammatory/autoimmune Disease: Current Evidence and Future Therapeutic Potential. Expert Rev. Clin. Immunol. 2015, 11(4), 457–465. DOI: 10.1586/1744666X.2015.1024110.

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