Physical Activity and Inflammation

  • Raffaele Di Fenza
  • Paolo FiorinaEmail author


Diabetes mellitus, referred to simply as diabetes, is a serious metabolic disorder that affects millions of people worldwide [1, 2]. It is caused by defects in insulin production, insulin secretion, and insulin signaling, all of which result in abnormally high blood sugar levels [3]. Diabetes patients usually develop serious secondary complications, especially involving the microvasculature but also cardiovascular disease, retinal damage, nerve damage, and kidney failure [4]. The two principal idiopathic forms of diabetes are known as types 1 and 2. Type 1 diabetes (T1D) is due to an autoimmune attack that leads to self-destruction of the insulin-producing β-cells of the pancreas. Type 2 diabetes (T2D) is caused by defects in insulin action and production, leading to insulin resistance, dyslipidemia, and impaired insulin secretion.


Insulin Resistance Insulin Sensitivity Exercise Training Adipose Tissue Inflammation Anabolic Stimulus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    The Action to Control Cardiovascular Risk in Diabetes Study G (2008) Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559CrossRefGoogle Scholar
  2. 2.
    Abdul-Ghani MA, DeFronzo RA (2009) plasma glucose concentration and prediction of future risk of type 2 diabetes. Diabetes Care 32:S194–S198PubMedCrossRefGoogle Scholar
  3. 3.
    DeFronzo RA (2010) Overview of newer agents: where treatment is going. Am J Med 123: S38–S48PubMedCrossRefGoogle Scholar
  4. 4.
    Nathan DM (1993) Long-Term complications of diabetes mellitus. N Engl J Med 328:1676–1685PubMedCrossRefGoogle Scholar
  5. 5.
    Pickup JC, Crook MA (1998) Is type II diabetes mellitus a disease of the innate immune system? Diabetologia 41:1241–1248PubMedCrossRefGoogle Scholar
  6. 6.
    Pickup JC, Mattock MB, Chusney GD, Burt D (1997) NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 40:1286–1292PubMedCrossRefGoogle Scholar
  7. 7.
    Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286:327–334PubMedCrossRefGoogle Scholar
  8. 8.
    Spranger J, Kroke A, Mohlig M, et al (2003) 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 52:812–817PubMedCrossRefGoogle Scholar
  9. 9.
    Schenk S, Saberi M, Olefsky JM (2008) Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest 118:2992–3002PubMedCrossRefGoogle Scholar
  10. 10.
    Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91PubMedCrossRefGoogle Scholar
  11. 11.
    Pickup JC (2004) Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 27:813–823PubMedCrossRefGoogle Scholar
  12. 12.
    Tanaka T, Itoh H, Doi K, et al (1999) Down regulation of peroxisome proliferator-activated receptorgamma expression by inflammatory cytokines and its reversal by thiazolidinediones. Diabetologia 42:702–710PubMedCrossRefGoogle Scholar
  13. 13.
    Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. The Journal of Clinical Investigation 116:1793–1801PubMedCrossRefGoogle Scholar
  14. 14.
    Tilg H, Moschen AR (2008) Inflammatory mechanisms in the regulation of insulin resistance. Mol Med 14:222–231PubMedCrossRefGoogle Scholar
  15. 15.
    Karin M, Takahashi T, Kapahi P, et al (z) Oxidative stress and gene expression: the AP-1 and NF-kappaB connections. Biofactors 15:87–89Google Scholar
  16. 16.
    Hosogai N, Fukuhara A, Oshima K, et al (2007) Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 56:901–911PubMedCrossRefGoogle Scholar
  17. 17.
    de Luca C, Olefsky JM (2008) Inflammation and insulin resistance. FEBS Lett 582: 97–105PubMedCrossRefGoogle Scholar
  18. 18.
    Sergeev P, Ris F, et al (2002) Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 110: 851–860PubMedGoogle Scholar
  19. 19.
    Prentki M, Nolan CJ (2006) Islet beta cell failure in type 2 diabetes. J Clin Invest 116: 1802–1812PubMedCrossRefGoogle Scholar
  20. 20.
    Lovis P, Roggli E, Laybutt DR, et al (z) Alterations in microRNA expression contribute to fatty acid-induced pancreatic beta-cell dysfunction. Diabetes 57: 2728–2736Google Scholar
  21. 21.
    Newsholme P, Keane D, Welters HJ, Morgan NG (2007) Life and death decisions of the pancreatic beta-cell: the role of fatty acids. Clin Sci (Lond) 112: 27–42CrossRefGoogle Scholar
  22. 22.
    Oberholzer J, Bucher P, Spinas GA, Donath MY (2003) Monounsaturated fatty acids prevent the deleterious effects of palmitate and high glucose on human pancreatic beta-cell turnover and function. Diabetes 52: 726–733PubMedCrossRefGoogle Scholar
  23. 23.
    Spinas GA, Dyntar D, Moritz W, Kaiser N, Donath MY (2001) Distinct effects of saturated and monounsaturated fatty acids on beta-cell turnover and function. Diabetes 50: 69–76PubMedCrossRefGoogle Scholar
  24. 24.
    Donath MY, Ehses JA, K, et al (2005) Mechanisms of beta-cell death in type 2 diabetes. Diabetes 54 Suppl 2: S108–113CrossRefGoogle Scholar
  25. 25.
    Solinas G, Vilcu C, Neels JG, et al (2007) JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity. Cell Metab 6: 386–397PubMedCrossRefGoogle Scholar
  26. 26.
    Arkan MC, Hevener AL, Greten FR, et al (2005) IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11: 191–198PubMedCrossRefGoogle Scholar
  27. 27.
    Larsen CM, Faulenbach M, Vaag A, et al (2007) Interleukin-1-Receptor Antagonist in Type 2 Diabetes Mellitus. N Engl J Med 356: 1517–1526PubMedCrossRefGoogle Scholar
  28. 28.
    Woods JA, Vieira VJ, Keylock KT (2009) Exercise, Inflammation, and Innate Immunity. Immunology and Allergy Clinics of North America 29: 381–393PubMedCrossRefGoogle Scholar
  29. 29.
    Kohut ML, Sim YJ, Yu S, Yoon KJ, Loiacono CM (2009) Chronic Exercise Reduces Illness Severity, Decreases Viral Load, and Results in Greater Anti-Inflammatory Effects than Acute Exercise during Influenza Infection. The Journal of Infectious Diseases 200: 1434–1442PubMedCrossRefGoogle Scholar
  30. 30.
    Mathur N, Pedersen BK (2008) Exercise as a Mean to Control Low-Grade Systemic Inflammation. Mediators of Inflammation 2008: 6CrossRefGoogle Scholar
  31. 31.
    Si-Young K, Tae-Won J, Young-Soo L, Hye-Kyung N, Young-Joon S, Wook S (2009) Effects of Exercise on Cyclooxygenase-2 Expression and Nuclear Factor-κB DNA Binding in Human Peripheral Blood Mononuclear Cells. Annals of the New York Academy of Sciences 1171: 464–471CrossRefGoogle Scholar
  32. 32.
    Starkie R, Ostrowski SR, Jauffred S, Febbraio M, Pedersen BK (2003) Exercise and IL-6 infusion inhibit endotoxin-induced TNF-α; production in humans. FASEB J 17:887–889Google Scholar
  33. 33.
    Ramos DS, Olivo CR, Quirino Santos Lopes FDTR, et al (2009) Low-Intensity Swimming Training Partially Inhibits Lipopolysaccharide-Induced Acute Lung Injury. Medicine & Science in Sports & Exercise 42: 113–119CrossRefGoogle Scholar
  34. 34.
    Jankord R, Jemiolo B (2004) Influence of Physical Activity on Serum IL-6 and IL-10 Levels in Healthy Older Men. Medicine & Science in Sports & Exercise 36: 960–964CrossRefGoogle Scholar
  35. 35.
    Pischon T, Hankinson SE, Hotamisligil GS, Rifai N, Rimm EB (2003) Leisure-Time Physical Activity and Reduced Plasma Levels of Obesity-Related Inflammatory Markers. Obesity 11: 1055–1064CrossRefGoogle Scholar
  36. 36.
    Verdaet D, Dendale P, De Bacquer D, Delanghe J, Block P, De Backer G (2004) Association between leisure time physical activity and markers of chronic inflammation related to coronary heart disease. Atherosclerosis 176: 303–310PubMedCrossRefGoogle Scholar
  37. 37.
    Albert MA, Glynn RJ, Ridker PM (2004) Effect of physical activity on serum C-reactive protein. The American Journal of Cardiology 93: 221–225PubMedCrossRefGoogle Scholar
  38. 38.
    Kim Y, Shin Y, Bae J, et al (2008) Beneficial effects of cardiac rehabilitation and exercise after percutaneous coronary intervention on hsCRP and inflammatory cytokines in CAD patients Pflügers Archiv European Journal of Physiology 455:1081–1088PubMedCrossRefGoogle Scholar
  39. 39.
    Niessner A, Richter B, Penka M, et al (2006) Endurance training reduces circulating inflammatory markers in persons at risk of coronary events: Impact on plaque stabilization? Atherosclerosis 186: 160–165PubMedCrossRefGoogle Scholar
  40. 40.
    Balagopal P, George D, Patton N, et al (z) Lifestyle-only intervention attenuates the inflammatory state associated with obesity: A randomized controlled study in adolescents. The Journal of Pediatrics 146: 342–348Google Scholar
  41. 41.
    Kelly AS, Wetzsteon RJ, Kaiser DR, Steinberger J, Bank AJ, Dengel DR (2004) Inflammation, insulin, and endothelial function in overweight children and adolescents: The role of exercise. The Journal of Pediatrics 145: 731–736PubMedCrossRefGoogle Scholar
  42. 42.
    Okita K, Nishijima H, Murakami T, et al (2004) Can Exercise Training With Weight Loss Lower Serum C-Reactive Protein Levels? Arterioscler Thromb Vasc Biol 24: 1868–1873PubMedCrossRefGoogle Scholar
  43. 43.
    Marcell TJ, McAuley KA, Traustadóttir T, Reaven PD (2005) Exercise training is not associated with improved levels of C-reactive protein or adiponectin. Metabolism 54: 533–541PubMedCrossRefGoogle Scholar
  44. 44.
    Smith JK, Dykes R, Douglas JE, Krishnaswamy G, Berk S (1999) Long-term Exercise and Atherogenic Activity of Blood Mononuclear Cells in Persons at Risk of Developing Ischemic Heart Disease. JAMA 281: 1722–1727PubMedCrossRefGoogle Scholar
  45. 45.
    Goldhammer E, Tanchilevitch A, Maor I, Beniamini Y, Rosenschein U, Sagiv M (2005) Exercise training modulates cytokines activity in coronary heart disease patients. International Journal of Cardiology 100: 93–99PubMedCrossRefGoogle Scholar
  46. 46.
    Fantuzzi G (2005) Adipose tissue, adipokines, and inflammation. Journal of Allergy and Clinical Immunology 115: 911–919PubMedCrossRefGoogle Scholar
  47. 47.
    Wang B, Wood I, Trayhurn P (2007) Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes. Pflügers Archiv European Journal of Physiology 455:479–492PubMedCrossRefGoogle Scholar
  48. 48.
    Fargnoli J, Sun Q, Olenczuk D, et al (2010) Resistin is associated with biomarkers of inflammation while total and high-molecular weight adiponectin are associated with biomarkers of inflammation, insulin resistance, and endothelial function. European Journal of Endocrinology 162: 281–288PubMedCrossRefGoogle Scholar
  49. 49.
    Carrel A, McVean J, Clark R, Peterson S, Eickhoff J, Allen D (2009) School-based Exercise Improves Fitness, Body Composition, Insulin Sensitivity, and Markers of Inflammation in Non-Obese Children. Journal of Pediatric Endocrinology & Metabolism 22: 409–415CrossRefGoogle Scholar
  50. 50.
    Weisberg S, McCann D, Desai M, Rosenbaum M, Leibel R, Ferrante Jr. A (2003) Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112: 1796–1808PubMedGoogle Scholar
  51. 51.
    Xu H, Barnes G, Yang Q, et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112: 1821–1830PubMedGoogle Scholar
  52. 52.
    Bouloumie A, Curat C, Sengene C, Lolme K, Miranvillea A, Bussea R (2005) Role of macrophage tissue infiltration in metabolic diseases. Curr Opin Clin Nutr Metab Care 8: 347–354PubMedCrossRefGoogle Scholar
  53. 53.
    Christiansen T, Richelsen B, Bruun J (2005) Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. International Journal of Obesity 29:146–150PubMedCrossRefGoogle Scholar
  54. 54.
    Pedersen B, Akerstrom T, Nielsen A, Fischer C (2007) Role of myokines in exercise and metabolism. J Appl Physiol 103: 1093–1098PubMedCrossRefGoogle Scholar
  55. 55.
    Esposito K, Pontillo A, Di Palo C, et al (2003) Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289:1799–1804PubMedCrossRefGoogle Scholar
  56. 56.
    Petersen E, Carey A, Sacchetti M (2005) Acute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitro. American Journal of Physiology 288: 155–161Google Scholar
  57. 57.
    Esposito K, Nappo F, Marfella R, et al (2002) Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans: Role of Oxidative Stress. Circulation 106: 2067–2072PubMedCrossRefGoogle Scholar
  58. 58.
    Sigal RJ, Kenny GP, Boule NG, et al (2007) Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial. Ann Intern Med 147: 357–369PubMedGoogle Scholar
  59. 59.
    Krutzfeldt J, Kuwajima S, Braich R, et al (2007) Specificity, duplex degradation and subcellular localization of antagomirs. Nucleic Acids Res 35: 2885–2892PubMedCrossRefGoogle Scholar
  60. 60.
    Bevilaqua MP, Pober JS, Wheeler ME, Cotran RS, Gimbrone Jr MA (1985) Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest 76:2003–2011CrossRefGoogle Scholar
  61. 61.
    Liu L, Zhang Y, Chen N, Shi X, Tsang B, Yu YH (2007) Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance. J Clin Invest 117: 1679–1689PubMedCrossRefGoogle Scholar
  62. 62.
    Ikeda S, Miyazaki H, Nakatani T, et al (2002) Up-regulation of SREBP-1c and lipogenic genes in skeletal muscles after exercise training. Biochem Biophys Res Commun 296: 395–400PubMedCrossRefGoogle Scholar
  63. 63.
    Bradley RL, Jeon JY, Liu FF, Maratos-Flier E (2008) Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice. Am J Physiol Endocrinol Metab 295: E586–594PubMedCrossRefGoogle Scholar
  64. 64.
    Rockl KS, Hirshman MF, Brandauer J, Fujii N, Witters LA, Goodyear LJ (2007) Skeletal muscle adaptation to exercise training: AMP-activated protein kinase mediates muscle fiber type shift. Diabetes 56: 2062–2069PubMedCrossRefGoogle Scholar
  65. 65.
    Zierath JR, Hawley JA (2004) Skeletal muscle fiber type: influence on contractile and metabolic properties. PLoS Biol 2: e348PubMedCrossRefGoogle Scholar
  66. 66.
    Kivelä R, Silvennoinen M, Lehti M, Jalava S, Vihko V, Kainulainen H (2008) Exercise-induced expression of angiogenic growth factors in skeletal muscle and in capillaries of healthy and diabetic mice. Cardiovasc Diabetol 7: 13PubMedCrossRefGoogle Scholar
  67. 67.
    Drummond MJ, McCarthy JJ, Fry CS, Esser KA, Rasmussen BB (2008) Aging differentially affects human skeletal muscle microRNA expression at rest and following resistance exercise and essential amino acid ingestion. Am J Physiol Endocrinol MetabGoogle Scholar
  68. 68.
    Nader GA, Lundberg IE (2009) Exercise as an anti-inflammatory intervention to combat inflammatory diseases of muscle. Curr Opin Rheumatol 21: 599–603 510.1097/BOR. 1090b1013e3283319d3283353PubMedCrossRefGoogle Scholar
  69. 69.
    Nathan DM, Buse JB, Davidson MB, et al (2009) Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy. Diabetes Care 32: 193–203PubMedCrossRefGoogle Scholar
  70. 70.
    Beavers KM, Brinkley TE, Nicklas BJ (2010) Effect of exercise training on chronic inflammation. Clinica Chimica Acta 411:785–793CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  1. 1.Harvard Medical SchoolBostonUSA
  2. 2.Department of MedicineIstituto Scientifico San RaffaeleMilanItaly

Personalised recommendations