Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2014, Article ID 479587, 12 pages
http://dx.doi.org/10.1155/2014/479587
Research Article

The Production of Nitric Oxide, IL-6, and TNF-Alpha in Palmitate-Stimulated PBMNCs Is Enhanced through Hyperglycemia in Diabetes

1Núcleo de Pós-Graduação e Pesquisa (NPGP), Hospital Santa Casa de Belo Horizonte, Domingos Vieira 590, Santa Efigênia, 30150-240 Belo Horizonte, MG, Brazil
2Centro Universitário de Belo Horizonte (UniBH), Professor Mário Werneck, 1685 Estoril, 30455-610 Belo Horizonte, MG, Brazil

Received 23 January 2014; Accepted 1 March 2014; Published 6 April 2014

Academic Editor: Daniela Giustarini

Copyright © 2014 Caroline Maria Oliveira Volpe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. N. Bergman and M. Ader, “Free fatty acids and pathogenesis of type 2 diabetes mellitus,” Trends in Endocrinology and Metabolism, vol. 11, no. 9, pp. 351–356, 2000. View at Publisher · View at Google Scholar · View at Scopus
  2. G. Boden, “Role of fatty acids in the pathogenesis of insulin resistance and NIDDM,” Diabetes, vol. 46, no. 1, pp. 3–10, 1997. View at Google Scholar · View at Scopus
  3. V. Stich and M. Berlan, “Physiological regulation of NEFA availability: lipolysis pathway,” Proceedings of the Nutrition Society, vol. 63, no. 2, pp. 369–374, 2004. View at Publisher · View at Google Scholar · View at Scopus
  4. S. Tsimikas and P. D. Reaven, “The role of dietary fatty acids in lipoprotein oxidation and atherosclerosis,” Current Opinion in Lipidology, vol. 9, no. 4, pp. 301–307, 1998. View at Publisher · View at Google Scholar · View at Scopus
  5. G. M. Reaven, “Role of insulin resistance in human disease,” Diabetes, vol. 37, no. 12, pp. 1595–1607, 1988. View at Google Scholar · View at Scopus
  6. T. Ulven, “Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets,” Frontiers in Endocrinology, vol. 3, p. 111, 2012. View at Google Scholar
  7. M. A. R. Vinolo, S. M. Hirabara, and R. Curi, “G-protein-coupled receptors as fat sensors,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 15, no. 2, pp. 112–116, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. R. C. Bunn, G. E. Cockrell, Y. Ou, K. M. Thrailkill, C. K. Lumpkin Jr., and J. L. Fowlkes, “Palmitate and insulin synergistically induce IL-6 expression in human monocytes,” Cardiovascular Diabetology, vol. 9, article no. 73, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. B. M. Egan, G. Lu, and E. L. Greene, “Vascular effects of non-esterified fatty acids: implications for the cardiovascular risk factor cluster,” Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 60, no. 5-6, pp. 411–420, 1999. View at Publisher · View at Google Scholar · View at Scopus
  10. B. Hennig, D. M. Shasby, and A. A. Spector, “Exposure to fatty acid increases human low density lipoprotein transfer across cultured endothelial monolayers,” Circulation Research, vol. 57, no. 5, pp. 776–780, 1985. View at Google Scholar · View at Scopus
  11. D. F. Horrobin, “Abnormal membrane concentrations of 20 and 22-carbon essential fatty acids: a common link between risk factors and coronary and peripheral vascular disease?” Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 53, no. 6, pp. 385–396, 1995. View at Publisher · View at Google Scholar · View at Scopus
  12. G. I. Shulman, “Cellular mechanisms of insulin resistance,” Journal of Clinical Investigation, vol. 106, no. 2, pp. 171–176, 2000. View at Google Scholar · View at Scopus
  13. D. Giugliano, A. Ceriello, and G. Paolisso, “Oxidative stress and diabetic vascular complications,” Diabetes Care, vol. 19, no. 3, pp. 257–267, 1996. View at Google Scholar · View at Scopus
  14. E. Hatanaka, A. C. Levada-Pires, T. C. Pithon-Curi, and R. Curi, “Systematic study on ROS production induced by oleic, linoleic, and γ-linolenic acids in human and rat neutrophils,” Free Radical Biology and Medicine, vol. 41, no. 7, pp. 1124–1132, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. U. Wenzel, A. Nickel, and H. Daniel, “Increased mitochondrial palmitoylcarnitine/carnitine countertransport by flavone causes oxidative stress and apoptosis in colon cancer cells,” Cellular and Molecular Life Sciences, vol. 62, no. 24, pp. 3100–3105, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. G. S. Dhaunsi, J. Kaur, K. Alsaeid, R. B. Turner, and M. S. Bitar, “Very long chain fatty acids activate NADPH oxidase in human dermal fibroblasts,” Cell Biochemistry and Function, vol. 23, no. 1, pp. 65–68, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. M. H. Horani, M. J. Haas, and A. D. Mooradian, “Saturated, unsaturated, and trans-fatty acids modulate oxidative burst induced by high dextrose in human umbilical vein endothelial cells,” Nutrition, vol. 22, no. 2, pp. 123–127, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. C. Duval, Y. Cámara, E. Hondares, B. Sibille, and F. Villarroya, “Overexpression of mitochondrial uncoupling protein-3 does not decrease production of the reactive oxygen species, elevated by palmitate in skeletal muscle cells,” FEBS Letters, vol. 581, no. 5, pp. 955–961, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Srivastava and C. Chan, “Hydrogen peroxide and hydroxyl radicals mediate palmitate-induced cytotoxicity to hepatoma cells: relation to mitochondrial permeability transition,” Free Radical Research, vol. 41, no. 1, pp. 38–49, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. L. I. Rachek, S. I. Musiyenko, S. P. LeDoux, and G. L. Wilson, “Palmitate induced mitochondrial deoxyribonucleic acid damage and apoptosis in L6 rat skeletal muscle cells,” Endocrinology, vol. 148, no. 1, pp. 293–299, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. M. R. Dasu and I. Jialal, “Free fatty acids in the presence of high glucose amplify monocyte inflammation via Toll-like receptors,” American Journal of Physiology, vol. 300, no. 1, pp. E145–E154, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. R. H. Lambertucci, S. M. Hirabara, L. D. R. Silveira, A. C. Levada-Pires, R. Curi, and T. C. Pithon-Curi, “Palmitate increases superoxide production through mitochondrial electron transport chain and NADPH oxidase activity in skeletal muscle cells,” Journal of Cellular Physiology, vol. 216, no. 3, pp. 796–804, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. V. Darley-Usmar, H. Wiseman, and B. Halliwell, “Nitric oxide and oxygen radicals: a question of balance,” FEBS Letters, vol. 369, no. 2-3, pp. 131–135, 1995. View at Publisher · View at Google Scholar · View at Scopus
  24. D. McGrowder, D. Ragoobirsingh, and P. Brown, “Acute effects of exogenous nitric oxide on glucose uptake in skeletal muscle of normoglycaemic and diabetic rats,” Medical Science Monitor, vol. 12, no. 1, pp. BR28–BR35, 2006. View at Google Scholar · View at Scopus
  25. M. J. Jackson, D. Pye, and J. Palomero, “The production of reactive oxygen and nitrogen species by skeletal muscle,” Journal of Applied Physiology, vol. 102, no. 4, pp. 1664–1670, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. D. M. Pattwell, A. McArdle, J. E. Morgan, T. A. Patridge, and M. J. Jackson, “Release of reactive oxygen and nitrogen species from contracting skeletal muscle cells,” Free Radical Biology and Medicine, vol. 37, pp. 1064–1072, 2004. View at Publisher · View at Google Scholar
  27. J. K. Kim, “Fat uses a TOLL-road to connect inflammation and diabetes,” Cell Metabolism, vol. 4, no. 6, pp. 417–419, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. T. Martins de Lima, R. Gorjão, E. Hatanaka et al., “Mechanisms by which fatty acids regulate leucocyte function,” Clinical Science, vol. 113, no. 1-2, pp. 65–77, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. H. Shi, M. V. Kokoeva, K. Inouye, I. Tzameli, H. Yin, and J. S. Flier, “TLR4 links innate immunity and fatty acid-induced insulin resistance,” Journal of Clinical Investigation, vol. 116, no. 11, pp. 3015–3025, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. L. A. Stoddart, N. J. Smith, and G. Milligan, “International union of pharmacology. LXXI. Free fatty acid receptors FFA1, -2, and -3: pharmacology and pathophysiological functions,” Pharmacological Reviews, vol. 60, no. 4, pp. 405–417, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. H. Kolb and T. Mandrup-Poulsen, “An immune origin of type 2 diabetes?” Diabetologia, vol. 48, no. 6, pp. 1038–1050, 2005. View at Publisher · View at Google Scholar · View at Scopus
  32. D. Tripathy, P. Mohanty, S. Dhindsa et al., “Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects,” Diabetes, vol. 52, no. 12, pp. 2882–2887, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. Y. Azekoshi, T. Yasu, S. Watanabe et al., “Free fatty acid causes leukocyte activation and resultant endothelial dysfunction through enhanced angiotensin II production in mononuclear and polymorphonuclear cells,” Hypertension, vol. 56, no. 1, pp. 136–142, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Morohoshi, K. Fujisawa, I. Uchimura, and F. Numano, “Glucose-dependent interleukin 6 and tumor necrosis factor production by human peripheral blood monocytes in vitro,” Diabetes, vol. 45, no. 3, pp. 954–959, 1996. View at Google Scholar · View at Scopus
  35. M. R. Dasu, S. Devaraj, L. Zhao, D. H. Hwang, and I. Jialal, “High glucose induces toll-like receptor expression in human monocytes mechanism of activation,” Diabetes, vol. 57, no. 11, pp. 3090–3098, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. T. Inoguchi, P. Li, F. Umeda et al., “High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells,” Diabetes, vol. 49, no. 11, pp. 1939–1945, 2000. View at Google Scholar · View at Scopus
  37. L. Håversen, K. N. Danielsson, L. Fogelstrand, and O. Wiklund, “Induction of proinflammatory cytokines by long-chain saturated fatty acids in human macrophages,” Atherosclerosis, vol. 202, no. 2, pp. 382–393, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Morigi, S. Angioletti, B. Imberti et al., “Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion,” Journal of Clinical Investigation, vol. 101, no. 9, pp. 1905–1915, 1998. View at Google Scholar · View at Scopus
  39. M. Guha, W. Bai, J. L. Nadler, and R. Natarajan, “Molecular mechanisms of tumor necrosis factor α gene expression in monocytic cells via hyperglycemia-induced oxidant stress-dependent and -independent pathways,” Journal of Biological Chemistry, vol. 275, no. 23, pp. 17728–17739, 2000. View at Publisher · View at Google Scholar · View at Scopus
  40. P. S. Laine, E. A. Schwartz, Y. Wang et al., “Palmitic acid induces IP-10 expression in human macrophages via NF-κB activation,” Biochemical and Biophysical Research Communications, vol. 358, no. 1, pp. 150–155, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. J. Y. Lee, J. Ye, Z. Gao et al., “Reciprocal modulation of toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT by saturated and polyunsaturated fatty acids,” Journal of Biological Chemistry, vol. 278, no. 39, pp. 37041–37051, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. E. Maloney, I. R. Sweet, D. M. Hockenbery et al., “Activation of NF-κB by palmitate in endothelial cells: a key role for NADPH oxidase-derived superoxide in response to TLR4 activation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 9, pp. 1370–1375, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. D. K. Covington, C. A. Briscoe, A. J. Brown, and C. K. Jayawickreme, “The G-protein-coupled receptor 40 family (GPR40-GPR43) and its role in nutrient sensing,” Biochemical Society Transactions, vol. 34, no. 5, pp. 770–773, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. S. M. Grundy and M. A. Denke, “Dietary influences on serum lipids and lipoproteins,” Journal of Lipid Research, vol. 31, no. 7, pp. 1149–1172, 1990. View at Google Scholar · View at Scopus
  45. G. V. Richieri and A. M. Kleinfeld, “Unbound free fatty acid levels in human serum,” Journal of Lipid Research, vol. 36, no. 2, pp. 229–240, 1995. View at Google Scholar · View at Scopus
  46. “Diagnosis and classification of diabetes mellitus,” Diabetes Care, vol. 33, supplement 1, pp. S62–S69, 2010.
  47. S. P. Cousin, S. R. Hügl, C. E. Wrede, H. Kajio, M. G. Myers Jr., and C. J. Rhodes, “Free fatty acid-induced inhibition of glucose and insulin-like growth factor I-induced deoxyribonucleic acid synthesis in the pancreatic β-cell line INS-1,” Endocrinology, vol. 142, no. 1, pp. 229–240, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. H. M. S. Bicalho, C. M. Gontijo, and J. A. Nogueira-Machado, “A simple technique for simultaneous human leukocytes separation,” Journal of Immunological Methods, vol. 40, no. 1, pp. 115–116, 1981. View at Publisher · View at Google Scholar · View at Scopus
  49. M. A. Creager, T. F. Lüscher, F. Cosentino, and J. A. Beckman, “Diabetes and vascular disease. Pathophysiology, clinical consequences, and medical therapy: part I,” Circulation, vol. 108, no. 12, pp. 1527–1532, 2003. View at Publisher · View at Google Scholar · View at Scopus
  50. N. Lamharzi, C. B. Renard, F. Kramer et al., “Hyperlipidemia in concert with hyperglycemia stimulates the proliferation of macrophages in atherosclerotic lesions: potential role of glucose-oxidized LDL,” Diabetes, vol. 53, no. 12, pp. 3217–3225, 2004. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Okuyama, T. Fujiwara, and J. Ohsumi, “High glucose potentiates palmitate-induced NO-mediated cytotoxicity through generation of superoxide in clonal β-cell HIT-T15,” FEBS Letters, vol. 545, no. 2-3, pp. 219–223, 2003. View at Publisher · View at Google Scholar · View at Scopus
  52. G. Boden, P. She, M. Mozzoli et al., “Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-κb pathway in rat liver,” Diabetes, vol. 54, no. 12, pp. 3458–3465, 2005. View at Publisher · View at Google Scholar · View at Scopus
  53. Z. Gao, X. Zhang, A. Zuberi et al., “Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocytes,” Molecular Endocrinology, vol. 18, no. 8, pp. 2024–2034, 2004. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Jové, A. Planavila, R. M. Sánchez, M. Merlos, J. C. Laguna, and M. Vázquez-Carrera, “Palmitate induces tumor necrosis factor-α expression in C2C12 skeletal muscle cells by a mechanism involving protein kinase C and nuclear factor-κB activation,” Endocrinology, vol. 147, no. 1, pp. 552–561, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. H. K. Takahashi, T. D. Cambiaghi, A. D. Luchessi et al., “Activation of survival and apoptotic signaling pathways in lymphocytes exposed to palmitic acid,” Journal of Cellular Physiology, vol. 227, no. 1, pp. 339–350, 2012. View at Publisher · View at Google Scholar · View at Scopus
  56. C. M. Sena, A. M. Pereira, and R. Seica, “Endothelial dysfunction—a major mediator of diabetic vascular disease,” Biochimica et Biophysica Acta, vol. 1832, pp. 2216–2231, 2013. View at Google Scholar
  57. T. Suganami, K. Tanimoto-Koyama, J. Nishida et al., “Role of the Toll-like receptor 4/NF-κB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 1, pp. 84–91, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. A. S. Baldwin Jr., “The NF-kappa B and I kappa B proteins: new discoveries and insights,” Annual Review of Immunology, vol. 14, pp. 649–683, 1996. View at Google Scholar
  59. K. E. Wellen and G. S. Hotamisligil, “Inflammation, stress, and diabetes,” Journal of Clinical Investigation, vol. 115, no. 5, pp. 1111–1119, 2005. View at Publisher · View at Google Scholar · View at Scopus
  60. H. L. Pahl, “Activators and target genes of Rel/NF-κB transcription factors,” Oncogene, vol. 18, no. 49, pp. 6853–6866, 1999. View at Google Scholar · View at Scopus
  61. P. Kubes, “Polymorphonuclear leukocyte-endothelium interactions: a role for pro-inflammatory and anti-inflammatory molecules,” Canadian Journal of Physiology and Pharmacology, vol. 71, no. 1, pp. 88–97, 1993. View at Google Scholar · View at Scopus
  62. J. MacMicking, Q.-W. Xie, and C. Nathan, “Nitric oxide and macrophage function,” Annual Review of Immunology, vol. 15, pp. 323–350, 1997. View at Publisher · View at Google Scholar · View at Scopus
  63. M. A. Marletta, A. R. Hurshman, and K. M. Rusche, “Catalysis by nitric oxide synthase,” Current Opinion in Chemical Biology, vol. 2, no. 5, pp. 656–663, 1998. View at Google Scholar · View at Scopus
  64. Z. Grozdanovic, “NO message from muscle,” Microscopy Research and Technique, vol. 55, no. 3, pp. 148–153, 2001. View at Publisher · View at Google Scholar · View at Scopus
  65. S. Moncada, R. M. J. Palmer, and E. A. Higgs, “Nitric oxide: physiology, pathophysiology, and pharmacology,” Pharmacological Reviews, vol. 43, no. 2, pp. 109–142, 1991. View at Google Scholar · View at Scopus
  66. C. Nathan and Q.-W. Xie, “Nitric oxide synthases: roles, tolls, and controls,” Cell, vol. 78, no. 6, pp. 915–918, 1994. View at Publisher · View at Google Scholar · View at Scopus
  67. R. H. Lambertucci, C. G. Leandro, M. A. Vinolo et al., “The effects of palmitic acid on nitric oxide production by rat skeletal muscle: mechanism via superoxide and iNOS activation,” Cellular Physiology and Biochemistry, vol. 30, pp. 1169–1180, 2012. View at Google Scholar
  68. V. E. Esenabhalu, G. Schaeffer, and W. F. Graier, “Free fatty acid overload attenuates Ca2+ signaling and NO production in endothelial cells,” Antioxidants and Redox Signaling, vol. 5, no. 2, pp. 147–153, 2003. View at Google Scholar · View at Scopus
  69. H. Li, H. Li, Y. Bao, X. Zhang, and Y. Yu, “Free fatty acids induce endothelial dysfunction and activate protein kinase C and nuclear factor-κB pathway in rat aorta,” International Journal of Cardiology, vol. 152, no. 2, pp. 218–224, 2011. View at Publisher · View at Google Scholar · View at Scopus
  70. Y. Tang and G. Li, “Chronic exposure to high fatty acids impedes receptor agonist-induced nitric oxide production and increments of cytosolic Ca2+ levels in endothelial cells,” Journal of Molecular Endocrinology, vol. 47, no. 3, pp. 315–326, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. F. Kim, K. A. Tysseling, J. Rice et al., “Free fatty acid impairment of nitric oxide production in endothelial cells is mediated by IKKβ,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 5, pp. 989–994, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. A. D. Meleth, E. Agrón, C.-C. Chan et al., “Serum inflammatory markers in diabetic retinopathy,” Investigative Ophthalmology and Visual Science, vol. 46, no. 11, pp. 4295–4301, 2005. View at Publisher · View at Google Scholar · View at Scopus
  73. A. Celebiler Cavusoglu, S. Bilgili, A. Alaluf et al., “Vascular endothelial growth factor level in the serum of diabetic patients with retinopathy,” Annals of Ophthalmology, vol. 39, no. 3, pp. 205–208, 2007. View at Publisher · View at Google Scholar · View at Scopus
  74. B. T. Ozturk, B. Bozkurt, H. Kerimoglu, M. Okka, U. Kamis, and K. Gunduz, “Effect of serum cytokines and VEGF levels on diabetic retinopathy and macular thickness,” Molecular Vision, vol. 15, pp. 1906–1914, 2009. View at Google Scholar · View at Scopus
  75. M. Kalousová, T. Zima, V. Tesař, S. Dusilová-Sulková, and J. Škrha, “Advanced glycoxidation end products in chronic diseases—clinical chemistry and genetic background,” Mutation Research, vol. 579, no. 1-2, pp. 37–46, 2005. View at Publisher · View at Google Scholar · View at Scopus
  76. K. Alexandraki, C. Piperi, C. Kalofoutis, J. Singh, A. Alaveras, and A. Kalofoutis, “Inflammatory process in type 2 diabetes: the role of cytokines,” Annals of the New York Academy of Sciences, vol. 1084, pp. 89–117, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. K. I. Alexandraki, C. Piperi, P. D. Ziakas et al., “Cytokine secretion in long-standing diabetes mellitus type 1 and 2: associations with low-grade systemic inflammation,” Journal of Clinical Immunology, vol. 28, no. 4, pp. 314–321, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. J. C. Pickup, “Inflammation and activated innate immunity in the pathogenesis of type 2 diabletes,” Diabetes Care, vol. 27, no. 3, pp. 813–823, 2004. View at Publisher · View at Google Scholar · View at Scopus
  79. J. C. Pickup, G. D. Chusney, S. M. Thomas, and D. Burt, “Plasma interleukin-6, tumour necrosis factor α and blood cytokine production in type 2 diabetes,” Life Sciences, vol. 67, no. 3, pp. 291–300, 2000. View at Publisher · View at Google Scholar · View at Scopus
  80. J. C. Pickup and M. A. Crook, “Is type II diabetes mellitus a disease of the innate immune system?” Diabetologia, vol. 41, no. 10, pp. 1241–1248, 1998. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Ceriello, “New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy,” Diabetes Care, vol. 26, no. 5, pp. 1589–1596, 2003. View at Publisher · View at Google Scholar · View at Scopus
  82. P. Dandona, A. Aljada, and A. Bandyopadhyay, “Inflammation: the link between insulin resistance, obesity and diabetes,” Trends in Immunology, vol. 25, no. 1, pp. 4–7, 2004. View at Publisher · View at Google Scholar · View at Scopus
  83. P. Dandona, A. Aljada, A. Chaudhuri, and A. Bandyopadhyay, “The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis-related complications in type 2 diabetes,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 6, pp. 2422–2429, 2003. View at Google Scholar · View at Scopus
  84. M. Y. Donath and S. E. Shoelson, “Type 2 diabetes as an inflammatory disease,” Nature Reviews Immunology, vol. 11, no. 2, pp. 98–107, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. R. Esper, J. Vilariño, R. Machado, and A. Paragano, “Endothelial dysfunction in normal and abnormal glucose metabolism,” Advances in Cardiology, vol. 45, pp. 17–43, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. E. Hatanaka, P. T. Monteagudo, M. S. M. Marrocos, and A. Campa, “Neutrophils and monocytes as potentially important sources of proinflammatory cytokines in diabetes,” Clinical and Experimental Immunology, vol. 146, no. 3, pp. 443–447, 2006. View at Publisher · View at Google Scholar · View at Scopus
  87. C. Herder, E. J. Brunner, W. Rathmann et al., “Elevated levels of the anti-inflammatory interleukin-1 receptor antagonist precede the onset of type 2 diabetes: the whitehall II study,” Diabetes Care, vol. 32, no. 3, pp. 421–423, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. C. Herder, T. Illig, W. Rathmann et al., “Inflammation and type 2 diabetes: results from KORA Augsburg,” Gesundheitswesen, vol. 67, no. 1, pp. S115–S121, 2005. View at Publisher · View at Google Scholar · View at Scopus
  89. S. Mirza, M. Hossain, C. Mathews et al., “Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: a cross-sectional study,” Cytokine, vol. 57, no. 1, pp. 136–142, 2012. View at Publisher · View at Google Scholar · View at Scopus
  90. P. Rösen, P. P. Nawroth, G. King, W. Möller, H.-J. Tritschler, and L. Packer, “The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a congress series sponsored by UNESCO-MCBN, the American diabetes association and the German diabetes society,” Diabetes/Metabolism Research and Reviews, vol. 17, no. 3, pp. 189–212, 2001. View at Publisher · View at Google Scholar · View at Scopus
  91. S. E. Shoelson, J. Lee, and A. B. Goldfine, “Inflammation and insulin resistance,” Journal of Clinical Investigation, vol. 116, no. 7, pp. 1793–1801, 2006. View at Publisher · View at Google Scholar · View at Scopus
  92. J. Spranger, A. Kroke, M. Möhlig 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, vol. 52, no. 3, pp. 812–817, 2003. View at Publisher · View at Google Scholar · View at Scopus
  93. M. A. Syed, E. Barinas-Mitchell, S. L. Pietropaolo et al., “Is type 2 diabetes a chronic inflammatory/autoimmune disease?” Diabetes, Nutrition and Metabolism, vol. 15, no. 2, pp. 68–83, 2002. View at Google Scholar · View at Scopus
  94. J. A. Beckman, M. A. Creager, and P. Libby, “Diabetes and atherosclerosis epidemiology, pathophysiology, and management,” Journal of the American Medical Association, vol. 287, no. 19, pp. 2570–2581, 2002. View at Google Scholar · View at Scopus
  95. R. W. Nesto, “Correlation between cardiovascular disease and diabetes mellitus: current concepts,” American Journal of Medicine, vol. 116, supplement 5A, pp. 11S–22S, 2004. View at Publisher · View at Google Scholar · View at Scopus
  96. J. McAndrew, R. P. Patel, H. Jo et al., “The interplay of nitric oxide and peroxynitrite with signal transduction pathways: implications for disease,” Seminars in Perinatology, vol. 21, no. 5, pp. 351–366, 1997. View at Publisher · View at Google Scholar · View at Scopus
  97. S. Bartesaghi, G. Ferrer-Sueta, G. Peluffo et al., “Protein tyrosine nitration in hydrophilic and hydrophobic environments,” Amino Acids, vol. 32, no. 4, pp. 501–515, 2007. View at Publisher · View at Google Scholar · View at Scopus
  98. R. Radi, “Nitric oxide, oxidants, and protein tyrosine nitration,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 12, pp. 4003–4008, 2004. View at Publisher · View at Google Scholar · View at Scopus
  99. V. Large and P. Arner, “Regulation of lipolysis in humans. Pathophysiological modulation in obesity diabetes, and hyperlipidaemia,” Diabetes and Metabolism, vol. 24, no. 5, pp. 409–418, 1998. View at Google Scholar · View at Scopus
  100. Y.-D. I. Chen, A. Golay, A. L. M. Swislocki, and G. M. Reaven, “Resistance to insulin suppression of plasma free fatty acid concentrations and insulin stimulation of glucose uptake in noninsulin-dependent diabetes mellitus,” Journal of Clinical Endocrinology and Metabolism, vol. 64, no. 1, pp. 17–21, 1987. View at Google Scholar · View at Scopus
  101. R. H. Unger, “Lipotoxicity in the pathogenesis of obesity-dependent NIDDM: genetic and clinical implications,” Diabetes, vol. 44, no. 8, pp. 863–870, 1995. View at Google Scholar · View at Scopus
  102. G. M. Reaven, C. Hollenbeck, C.-Y. Jeng, M. S. Wu, and Y.-D. I. Chen, “Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM,” Diabetes, vol. 37, no. 8, pp. 1020–1024, 1988. View at Google Scholar · View at Scopus
  103. G. Boden, “Fatty acids and insulin resistance,” Diabetes Care, vol. 19, no. 4, pp. 394–395, 1996. View at Google Scholar · View at Scopus
  104. A. Guilherme, J. V. Virbasius, V. Puri, and M. P. Czech, “Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes,” Nature Reviews Molecular Cell Biology, vol. 9, no. 5, pp. 367–377, 2008. View at Publisher · View at Google Scholar · View at Scopus
  105. H. Bays, L. Mandarino, and R. A. DeFronzo, “Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 2, pp. 463–478, 2004. View at Publisher · View at Google Scholar · View at Scopus