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Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked?

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Rehman, Kanwal, Akash, Muhammad Sajid Hamid·2016·Journal of Biomedical Science
DOI 10.1186/s12929-016-0303-y
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Abstract

BACKGROUND: Insulin resistance (IR) is one of the major hallmark for pathogenesis and etiology of type 2 diabetes mellitus (T2DM). IR is directly interlinked with various inflammatory responses which play crucial role in the development of IR. Inflammatory responses play a crucial role in the pathogenesis and development of IR which is one of the main causative factor for the etiology of T2DM. METHODS: A comprehensive online English literature was searched using various electronic search databases. Different search terms for pathogenesis of IR, role of various inflammatory responses were used and an advanced search was conducted by combining all the search fields in abstracts, keywords, and titles. RESULTS: We summarized the data from the searched articles and found that inflammatory responses activate the production of various pro-inflammatory mediators notably cytokines, chemokines and adipocytokines through the involvement of various transcriptional mediated molecular pathways, oxidative and metabolic stress. Overnutrition is one of the major causative factor that contributes to induce the state of low-grade inflammation due to which accumulation of elevated levels of glucose and/or lipids in blood stream occur that leads to the activation of various transcriptional mediated molecular and metabolic pathways. This results in the induction of various pro-inflammatory mediators that are decisively involved to provoke the pathogenesis of tissue-specific IR by interfering with insulin signaling pathways. Once IR is developed, it increases oxidative stress in β-cells of pancreatic islets and peripheral tissues which impairs insulin secretion, and insulin sensitivity in β-cells of pancreatic islets and peripheral tissues, respectively. Moreover, we also summarized the data regarding various treatment strategies of inflammatory responses-induced IR. CONCLUSIONS: In this article, we have briefly described that how pro-inflammatory mediators, oxidative stress, transcriptional mediated molecular and metabolic pathways are involved in the pathogenesis of tissues-specific IR. Moreover, based on recent investigations, we have also described that to counterfeit these inflammatory responses is one of the best treatment strategy to prevent the pathogenesis of IR through ameliorating the incidences of inflammatory responses.

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Research works printed but not linked: 124

  1. Moller DE. Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab. 2000;11(6):212–7. · DOI · Paper page
  2. Akash MSH, Shen Q, Rehman K, Chen S. Interleukin-1 receptor antagonist: a new therapy for type 2 diabetes mellitus. J Pharm Sci. 2012;101(5):1647–58. · DOI
  3. Rehman K. and Akash M.S.H. Nutrition and Diabetes Mellitus: How are They Interlinked? 2016;26(4):317–332.
  4. Kawazoe Y, Naka T, Fujimoto M, Kohzaki H, Morita Y, Narazaki M, Okumura K, Saitoh H, Nakagawa R, Uchiyama Y, Akira S, Kishimoto T. Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1)/suppressor of cytokine signaling 1 (SOCS1) inhibits insulin signal transduction pathway through modulating insulin receptor substrate 1 (IRS-1) phosphorylation. J Exp Med. 2001;193(2):263–9. · DOI · Paper page
  5. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence, Annals of the New York Academy of Sciences. 908th ed. 2000. p. 244–54.
  6. Albright JW, Albright JF. Soluble receptors and other substances that regulate proinflammatory cytokines in young and aging humans. J Gerontol A Biol Sci Med Sci. 2000;55(1):B20–25. · DOI
  7. Akash MSH, Rehman K, Chen S. An overview of valuable scientific models for diabetes mellitus. Curr Diabetes Rev. 2013;9(4):286–93. · DOI
  8. Akash MSH, Rehman K, Chen S. Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus. J Cell Biochem. 2013;114(3):525–31. · DOI · Paper page
  9. Festa A, D’Agostino Jr R, Tracy RP, Haffner SM. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes. 2002;51(4):1131–7. · DOI · Paper page
  10. Pickup JC, Crook MA. Is type II diabetes mellitus a disease of the innate immune system? Diabetologia. 1998;41(10):1241–8. · DOI · Paper page
  11. Jager J, Gremeaux T, Cormont M, Le Marchand-Brustel Y, Tanti JF. Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology. 2007;148(1):241–51. · DOI · Paper page
  12. Donath MY, Boni-Schnetzler M, Ellingsgaard H, Ehses JA. Islet inflammation impairs the pancreatic beta-cell in type 2 diabetes. Physiology (Bethesda). 2009;24:325–31. · DOI · Paper page
  13. Abbatecola AM, Ferrucci L, Grella R, Bandinelli S, Bonafe M, Barbieri M, Corsi AM, Lauretani F, Franceschi C, Paolisso G. Diverse effect of inflammatory markers on insulin resistance and insulin-resistance syndrome in the elderly. J Am Geriatr Soc. 2004;52(3):399–404. · DOI · Paper page
  14. Bastard JP, Maachi M, Van Nhieu JT, Jardel C, Bruckert E, Grimaldi A, Robert JJ, Capeau J, Hainque B. Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab. 2002;87(5):2084–9. · DOI · Paper page
  15. Pickup JC, Mattock MB, Chusney GD, Burt D. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia. 1997;40(11):1286–92. · DOI · Paper page
  16. Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab. 2001;280(5):E745–751. · DOI · Paper page
  17. Kirwan JP, Jing M. Modulation of insulin signaling in human skeletal muscle in response to exercise. Exerc Sport Sci Rev. 2002;30(2):85–90. · DOI
  18. Emanuelli B, Peraldi P, Filloux C, Sawka-Verhelle D, Hilton D, Van Obberghen E. SOCS-3 is an insulin-induced negative regulator of insulin signaling. J Biol Chem. 2000;275(21):15985–91. · DOI · Paper page
  19. Hwa V, Nadeau K, Wit JM, Rosenfeld RG. STAT5b deficiency: lessons from STAT5b gene mutations. Best Pract Res Clin Endocrinol Metab. 2011;25(1):61–75. · DOI
  20. Akash MSH, Rehman K, Chen S. IL-1Ra and its delivery strategies: inserting the association in perspective. Pharm Res. 2013;30(11):2951–66. · DOI
  21. Akash MSH, Rehman K, Li N, Gao JQ, Sun H, Chen S. Sustained delivery of IL-1Ra from pluronic F127-based thermosensitive gel prolongs its therapeutic potentials. Pharm Res. 2012;29(12):3475–85. · DOI
  22. Akash MSH, Rehman K, Sun H, Chen S. Sustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats. PLoS One. 2013;8(2):e55925. · DOI
  23. Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GM. The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J. 2001;15(1):43–58. · DOI · Paper page
  24. Ogata A, Morishima A, Hirano T, Hishitani Y, Hagihara K, Shima Y, Narazaki M, Tanaka T. Improvement of HbA1c during treatment with humanised anti-interleukin 6 receptor antibody, tocilizumab. Ann Rheum Dis. 2011;70(6):1164–5. · DOI
  25. Nieto-Vazquez I, Fernandez-Veledo S, Kramer DK, Vila-Bedmar R, Garcia-Guerra L, Lorenzo M. Insulin resistance associated to obesity: the link TNF-alpha. Arch Physiol Biochem. 2008;114(3):183–94. · DOI · Paper page
  26. Swaroop JJ, Rajarajeswari D, Naidu JN. Association of TNF-alpha with insulin resistance in type 2 diabetes mellitus. Indian J Med Res. 2012;135:127–30. · DOI · Paper page
  27. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259(5091):87–91. · DOI · Paper page
  28. Chen G, Goeddel DV. TNF-R1 signaling: a beautiful pathway. Science. 2002;296(5573):1634–5. · DOI · Paper page
  29. Sharma R, Anker SD. Cytokines, apoptosis and cachexia: the potential for TNF antagonism. Int J Cardiol. 2002;85(1):161–71. · DOI
  30. Trayhurn P. Endocrine and signalling role of adipose tissue: new perspectives on fat. Acta Physiol Scand. 2005;184(4):285–93. · DOI · Paper page
  31. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548–56. · DOI · Paper page
  32. Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci U S A. 2003;100(12):7265–70. · DOI · Paper page
  33. Argiles JM, Lopez-Soriano J, Almendro V, Busquets S, Lopez-Soriano FJ. Cross-talk between skeletal muscle and adipose tissue: a link with obesity? Med Res Rev. 2005;25(1):49–65. · DOI · Paper page
  34. Krebs M, Roden M. Molecular mechanisms of lipid-induced insulin resistance in muscle, liver and vasculature. Diabetes Obes Metab. 2005;7(6):621–32. · DOI
  35. Sjoholm A, Nystrom T. Inflammation and the etiology of type 2 diabetes. Diabetes Metab Res Rev. 2006;22(1):4–10. · DOI · Paper page
  36. Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest. 2000;106(4):473–81. · DOI · Paper page
  37. Zhang F, Chen Y, Heiman M, Dimarchi R. Leptin: structure, function and biology. Vitam Horm. 2005;71:345–72. · DOI · Paper page
  38. Tschritter O, Fritsche A, Thamer C, Haap M, Shirkavand F, Rahe S, Staiger H, Maerker E, Haring H, Stumvoll M. Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism. Diabetes. 2003;52(2):239–43. · DOI · Paper page
  39. Ota T. Chemokine systems link obesity to insulin resistance. Diabetes Metab J. 2013;37(3):165–72. · DOI
  40. Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe T, Kubota N, Ohtsuka-Kowatari N, Kumagai K, Sakamoto K, Kobayashi M, Yamauchi T, Ueki K, Oishi Y, Nishimura S, Manabe I, Hashimoto H, Ohnishi Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Nagai R, Kadowaki T. Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem. 2006;281(36):26602–14. · DOI · Paper page
  41. Xu L, Kitade H, Ni Y, Ota T. Roles of Chem okines and Chemokine Receptors in Obesity-Associated Insulin Resistance and Nonalcoholic Fatty Liver Disease. Biomolecules 2015;5(3):1563-1579. · DOI · Paper page
  42. Kitade H, Sawamoto K, Nagashimada M, Inoue H, Yamamoto Y, Sai Y, Takamura T, Yamamoto H, Miyamoto K, Ginsberg HN, Mukaida N, Kaneko S, Ota T. CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status. Diabetes. 2012;61(7):1680–90. · DOI · Paper page
  43. Gerhardt CC, Romero IA, Cancello R, Camoin L, Strosberg AD. Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol Cell Endocrinol. 2001;175(1–2):81–92. · DOI · Paper page
  44. Moran A, Steffen LM, Jacobs Jr DR, Steinberger J, Pankow JS, Hong CP, Tracy RP, Sinaiko AR. Relation of C-reactive protein to insulin resistance and cardiovascular risk factors in youth. Diabetes Care. 2005;28(7):1763–8. · DOI
  45. Ridker PM. C-reactive protein and the prediction of cardiovascular events among those at intermediate risk: moving an inflammatory hypothesis toward consensus. J Am Coll Cardiol. 2007;49(21):2129–38. · DOI · Paper page
  46. Nakanishi N, Shiraishi T, Wada M. Association between C-reactive protein and insulin resistance in a Japanese population: the Minoh Study. Intern Med. 2005;44(6):542–7. · DOI
  47. Ndumele CE, Pradhan AD, Ridker PM. Interrelationships between inflammation, C-reactive protein, and insulin resistance. J Cardiometab Syndr. 2006;1(3):190–6. · DOI
  48. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286(3):327–34. · DOI · Paper page
  49. Hennig B, Meerarani P, Ramadass P, Watkins BA, Toborek M. Fatty acid-mediated activation of vascular endothelial cells. Metabolism. 2000;49(8):1006–13. · DOI
  50. Stuhlinger MC, Abbasi F, Chu JW, Lamendola C, McLaughlin TL, Cooke JP, Reaven GM, Tsao PS. Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA. 2002;287(11):1420–6. · DOI · Paper page
  51. Arcaro G, Cretti A, Balzano S, Lechi A, Muggeo M, Bonora E, Bonadonna RC. Insulin causes endothelial dysfunction in humans: sites and mechanisms. Circulation. 2002;105(5):576–82. · DOI · Paper page
  52. Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Gorgun C, Glimcher LH, Hotamisligil GS. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004;306(5695):457–61. · DOI · Paper page
  53. Boden G. Endoplasmic reticulum stress: another link between obesity and insulin resistance/inflammation? Diabetes. 2009;58(3):518–9. · DOI
  54. Salvado L, Palomer X, Barroso E, Vazquez-Carrera M. Targeting endoplasmic reticulum stress in insulin resistance. Trends Endocrinol Metab. 2015;26(8):438–48. · DOI · Paper page
  55. Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336(15):1066–71. · DOI · Paper page
  56. Chen LW, Egan L, Li ZW, Greten FR, Kagnoff MF, Karin M. The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion. Nat Med. 2003;9(5):575–81. · DOI · Paper page
  57. Li Q, Van Antwerp D, Mercurio F, Lee KF, Verma IM. Severe liver degeneration in mice lacking the IkappaB kinase 2 gene. Science. 1999;284(5412):321–5. · DOI · Paper page
  58. Grimble RF. Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care. 2002;5(5):551–9. · DOI · Paper page
  59. Klover PJ, Zimmers TA, Koniaris LG, Mooney RA. Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes. 2003;52(11):2784–9. · DOI · Paper page
  60. Karin M, Yamamoto Y, Wang QM. The IKK NF-kappa B system: a treasure trove for drug development. Nat Rev Drug Discov. 2004;3(1):17–26. · DOI · Paper page
  61. Arena FP, Dugowson C, Saudek CD. Salicylate-induced hypoglycemia and ketoacidosis in a nondiabetic adult. Arch Intern Med. 1978;138(7):1153–4. · DOI
  62. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219–46. · DOI · Paper page
  63. Kim JJ, Sears DD. TLR4 and Insulin Resistance. Gastroenterology Research and Practice. 2010: doi: 10.1155/2010/212563 . · DOI · Paper page
  64. Huang H, Park PH, McMullen MR, Nagy LE. Mechanisms for the anti-inflammatory effects of adiponectin in macrophages. J Gastroenterol Hepatol. 2008;23(s1):S50–3. · DOI
  65. Mandal P, Park PH, McMullen MR, Pratt BT, Nagy LE. The anti-inflammatory effects of adiponectin are mediated via a heme oxygenase-1-dependent pathway in rat Kupffer cells. Hepatology. 2010;51(4):1420–9. · DOI
  66. Yamaguchi N, Argueta JG, Masuhiro Y, Kagishita M, Nonaka K, Saito T, Hanazawa S, Yamashita Y. Adiponectin inhibits Toll-like receptor family-induced signaling. FEBS Lett. 2005;579(30):6821–6. · DOI · Paper page
  67. Jones LA, Anthony JP, Henriquez FL, Lyons RE, Nickdel MB, Carter KC, Alexander J, Roberts CW. Toll-like receptor-4-mediated macrophage activation is differentially regulated by progesterone via the glucocorticoid and progesterone receptors. Immunology. 2008;125(1):59–69. · DOI
  68. Reynolds CM, Draper E, Keogh B, Rahman A, Moloney AP, Mills KH, Loscher CE, Roche HM. A conjugated linoleic acid-enriched beef diet attenuates lipopolysaccharide-induced inflammation in mice in part through PPARgamma-mediated suppression of toll-like receptor 4. J Nutr. 2009;139(12):2351–7. · DOI
  69. Pocai A, Morgan K, Buettner C, Gutierrez-Juarez R, Obici S, Rossetti L. Central leptin acutely reverses diet-induced hepatic insulin resistance. Diabetes. 2005;54(11):3182–9. · DOI · Paper page
  70. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2010;316(2):129–39. · DOI · Paper page
  71. Lin Y, Lee H, Berg AH, Lisanti MP, Shapiro L, Scherer PE. The lipopolysaccharide-activated toll-like receptor (TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes. J Biol Chem. 2000;275(32):24255–63. · DOI · Paper page
  72. Poggi M, Bastelica D, Gual P, Iglesias MA, Gremeaux T, Knauf C, Peiretti F, Verdier M, Juhan-Vague I, Tanti JF, Burcelin R, Alessi MC. C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet. Diabetologia. 2007;50(6):1267–76. · DOI · Paper page
  73. Suganami T, Mieda T, Itoh M, Shimoda Y, Kamei Y, Ogawa Y. Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation. Biochem Biophys Res Commun. 2007;354(1):45–9. · DOI · Paper page
  74. Tsukumo DM, Carvalho-Filho MA, Carvalheira JB, Prada PO, Hirabara SM, Schenka AA, Araujo EP, Vassallo J, Curi R, Velloso LA, Saad MJ. Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes. 2007;56(8):1986–98. · DOI · Paper page
  75. Baron AD, Brechtel G, Wallace P, Edelman SV. Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans. Am J Physiol. 1988;255(6 Pt 1):E769–774.
  76. Wei Y, Chen K, Whaley-Connell AT, Stump CS, Ibdah JA, Sowers JR. Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species. American journal of physiology. Regul Integr Comp Physiol. 2008;294(3):R673–680. · DOI · Paper page
  77. Baffy G. Kupffer cells in non-alcoholic fatty liver disease: the emerging view. J Hepatol. 2009;51(1):212–23. · DOI · Paper page
  78. Spruss A, Kanuri G, Wagnerberger S, Haub S, Bischoff SC, Bergheim I. Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice. Hepatology. 2009;50(4):1094–104. · DOI · Paper page
  79. Videla LA, Tapia G, Rodrigo R, Pettinelli P, Haim D, Santibanez C, Araya AV, Smok G, Csendes A, Gutierrez L, Rojas J, Castillo J, Korn O, Maluenda F, Diaz JC, Rencoret G, Poniachik J. Liver NF-kappaB and AP-1 DNA binding in obese patients. Obesity. 2009;17(5):973–9. · DOI
  80. Raetzsch CF, Brooks NL, Alderman JM, Moore KS, Hosick PA, Klebanov S, Akira S, Bear JE, Baldwin AS, Mackman N, Combs TP. Lipopolysaccharide inhibition of glucose production through the Toll-like receptor-4, myeloid differentiation factor 88, and nuclear factor kappa b pathway. Hepatology. 2009;50(2):592–600. · DOI
  81. Wen L, Peng J, Li Z, Wong FS. The effect of innate immunity on autoimmune diabetes and the expression of Toll-like receptors on pancreatic islets. J Immunol. 2004;172(5):3173–80. · DOI
  82. Goldberg A, Parolini M, Chin BY, Czismadia E, Otterbein LE, Bach FH, Wang H. Toll-like receptor 4 suppression leads to islet allograft survival. FASEB J. 2007;21(11):2840–8. · DOI
  83. Kim F, Pham M, Luttrell I, Bannerman DD, Tupper J, Thaler J, Hawn TR, Raines EW, Schwartz MW. Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity. Circ Res. 2007;100(11):1589–96. · DOI · Paper page
  84. Wong FS, Hu C, Zhang L, Du W, Alexopoulou L, Flavell RA, Wen L. The role of Toll-like receptors 3 and 9 in the development of autoimmune diabetes in NOD mice. Ann N Y Acad Sci. 2008;1150:146–8. · DOI
  85. Boni-Schnetzler M, Boller S, Debray S, Bouzakri K, Meier DT, Prazak R, Kerr-Conte J, Pattou F, Ehses JA, Schuit FC, Donath MY. Free fatty acids induce a proinflammatory response in islets via the abundantly expressed interleukin-1 receptor I. Endocrinology. 2009;150(12):5218–29. · DOI · Paper page
  86. Schulthess FT, Paroni F, Sauter NS, Shu L, Ribaux P, Haataja L, Strieter RM, Oberholzer J, King CC, Maedler K. CXCL10 impairs beta cell function and viability in diabetes through TLR4 signaling. Cell Metab. 2009;9(2):125–39. · DOI · Paper page
  87. Sandoval DA, Obici S, Seeley RJ. Targeting the CNS to treat type 2 diabetes. Nat Rev Drug Discov. 2009;8(5):386–98. · DOI
  88. De Souza CT, Araujo EP, Bordin S, Ashimine R, Zollner RL, Boschero AC, Saad MJ, Velloso LA. Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology. 2005;146(10):4192–9. · DOI · Paper page
  89. Moraes JC, Coope A, Morari J, Cintra DE, Roman EA, Pauli JR, Romanatto T, Carvalheira JB, Oliveira AL, Saad MJ, Velloso LA. High-fat diet induces apoptosis of hypothalamic neurons. PLoS One. 2009;4(4):e5045. · DOI · Paper page
  90. Kim F, Tysseling KA, Rice J, Pham M, Haji L, Gallis BM, Baas AS, Paramsothy P, Giachelli CM, Corson MA, Raines EW. Free fatty acid impairment of nitric oxide production in endothelial cells is mediated by IKKbeta. Arterioscler Thromb Vasc Biol. 2005;25(5):989–94. · DOI · Paper page
  91. Li X, Tupper JC, Bannerman DD, Winn RK, Rhodes CJ, Harlan JM. Phosphoinositide 3 kinase mediates Toll-like receptor 4-induced activation of NF-kappa B in endothelial cells. Infect Immun. 2003;71(8):4414–20. · DOI
  92. Lee JY, Zhao L, Youn HS, Weatherill AR, Tapping R, Feng L, Lee WH, Fitzgerald KA, Hwang DH. Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J Biol Chem. 2004;279(17):16971–9. · DOI · Paper page
  93. Kim HS, Han MS, Chung KW, Kim S, Kim E, Kim MJ, Jang E, Lee HA, Youn J, Akira S, Lee MS. Toll-like receptor 2 senses beta-cell death and contributes to the initiation of autoimmune diabetes. Immunity. 2007;27(2):321–33. · DOI · Paper page
  94. Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, Mu J, Foufelle F, Ferre P, Birnbaum MJ, Stuck BJ, Kahn BB. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature. 2004;428(6982):569–74. · DOI · Paper page
  95. Ruderman NB, Carling D, Prentki M, Cacicedo JM. AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest. 2013;123(7):2764–72. · DOI · Paper page
  96. Srivastava RA, Pinkosky SL, Filippov S, Hanselman JC, Cramer CT, Newton RS. AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases. J Lipid Res. 2012;53(12):2490–514. · DOI · Paper page
  97. Steinberg GR, Kemp BE. AMPK in Health and Disease. Physiol Rev. 2009;89(3):1025–78. · DOI · Paper page
  98. Daval M, Foufelle F, Ferre P. Functions of AMP-activated protein kinase in adipose tissue. J Physiol. 2006;574(Pt 1):55–62. · DOI · Paper page
  99. Choudhury M, Qadri I, Rahman SM, Schroeder-Gloeckler J, Janssen RC, Friedman JE. C/EBPbeta is AMP kinase sensitive and up-regulates PEPCK in response to ER stress in hepatoma cells. Mol Cell Endocrinol. 2011;331(1):102–8. · DOI
  100. Dolinsky VW, Chan AY, Robillard FI, Light PE, Des RC, Dyck JR. Resveratrol prevents the prohypertrophic effects of oxidative stress on LKB1. Circulation. 2009;119(12):1643–52. · DOI · Paper page
  101. Salminen A, Hyttinen JM, Kaarniranta K. AMP-activated protein kinase inhibits NF-kappaB signaling and inflammation: impact on healthspan and lifespan. J Mol Med. 2011;89(7):667–76. · DOI · Paper page
  102. Coughlan KA, Valentine RJ, Ruderman NB, Saha AK. Nutrient Excess in AMPK Downregulation and Insulin Resistance. J Endocrino Diabetes Obesity. 2013;1(1):1008.
  103. Haasch D, Berg C, Clampit JE, Pederson T, Frost L, Kroeger P, Rondinone CM. PKCtheta is a key player in the development of insulin resistance. Biochem Biophys Res Commun. 2006;343(2):361–8. · DOI
  104. Gao Z, Zhang X, Zuberi A, Hwang D, Quon MJ, Lefevre M, Ye J. Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocytes. Mol Endocrinol. 2004;18(8):2024–34. · DOI · Paper page
  105. Dietze D, Ramrath S, Ritzeler O, Tennagels N, Hauner H, Eckel J. Inhibitor kappaB kinase is involved in the paracrine crosstalk between human fat and muscle cells. Int J Obes Relat Metab Disord. 2004;28(8):985–92. · DOI
  106. Lappas M, Yee K, Permezel M, Rice GE. Sulfasalazine and BAY 11–7082 interfere with the nuclear factor-kappa B and I kappa B kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro. Endocrinology. 2005;146(3):1491–7. · DOI
  107. Assimacopoulos-Jeannet F. Fat storage in pancreas and in insulin-sensitive tissues in pathogenesis of type 2 diabetes. Int J Obes Relat Metab Disord. 2004;28 Suppl 4:S53–57. · DOI
  108. Akash MSH, Rehman K, Sun H, Chen S. Interleukin-1 receptor antagonist improves normoglycemia and insulin sensitivity in diabetic Goto-Kakizaki-rats. Eur J Pharmacol. 2013;701(1–3):87–95. · DOI
  109. Ehses JA, Lacraz G, Giroix MH, Schmidlin F, Coulaud J, Kassis N, Irminger JC, Kergoat M, Portha B, Homo-Delarche F, Donath MY. IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat. Proc Natl Acad Sci U S A. 2009;106(33):13998–4003. · DOI · Paper page
  110. Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care. 2008;31(2):289–94. · DOI · Paper page
  111. Barbuio R, Milanski M, Bertolo MB, Saad MJ, Velloso LA. Infliximab reverses steatosis and improves insulin signal transduction in liver of rats fed a high-fat diet. J Endocrinol. 2007;194(3):539–50. · DOI · Paper page
  112. Lo J, Bernstein LE, Canavan B, Torriani M, Jackson MB, Ahima RS, Grinspoon SK. Effects of TNF-alpha neutralization on adipocytokines and skeletal muscle adiposity in the metabolic syndrome. Am J Physiol Endocrinol Metab. 2007;293(1):E102–109. · DOI
  113. Ventre J, Doebber T, Wu M, MacNaul K, Stevens K, Pasparakis M, Kollias G, Moller DE. Targeted disruption of the tumor necrosis factor-alpha gene: metabolic consequences in obese and nonobese mice. Diabetes. 1997;46(9):1526–31. · DOI · Paper page
  114. Borst SE, Bagby GJ. Neutralization of tumor necrosis factor reverses age-induced impairment of insulin responsiveness in skeletal muscle of Sprague–Dawley rats. Metabolism. 2002;51(8):1061–4. · DOI
  115. Cheung AT, Ree D, Kolls JK, Fuselier J, Coy DH, Bryer-Ash M. An in vivo model for elucidation of the mechanism of tumor necrosis factor-alpha (TNF-alpha)-induced insulin resistance: evidence for differential regulation of insulin signaling by TNF-alpha. Endocrinology. 1998;139(12):4928–35. · DOI
  116. Rosenvinge A, Krogh-Madsen R, Baslund B, Pedersen BK. Insulin resistance in patients with rheumatoid arthritis: effect of anti-TNFalpha therapy. Scand J Rheumatol. 2007;36(2):91–6. · DOI
  117. Eheim A, Medrikova D, Herzig S. Immune cells and metabolic dysfunction. Semin Immunopathol. 2014;36(1):13–25. · DOI
  118. Tamura Y, Sugimoto M, Murayama T, Minami M, Nishikaze Y, Ariyasu H, Akamizu T, Kita T, Yokode M, Arai H. C-C chemokine receptor 2 inhibitor improves diet-induced development of insulin resistance and hepatic steatosis in mice. J Atheroscler Thromb. 2010;17(3):219–28. · DOI
  119. Tamura Y, Sugimoto M, Murayama T, Ueda Y, Kanamori H, Ono K, Ariyasu H, Akamizu T, Kita T, Yokode M, Arai H. Inhibition of CCR2 ameliorates insulin resistance and hepatic steatosis in db/db mice. Arterioscler Thromb Vasc Biol. 2008;28(12):2195–201. · DOI
  120. Chavey C, Lazennec G, Lagarrigue S, Clape C, Iankova I, Teyssier J, Annicotte JS, Schmidt J, Mataki C, Yamamoto H, Sanches R, Guma A, Stich V, Vitkova M, Jardin-Watelet B, Renard E, Strieter R, Tuthill A, Hotamisligil GS, Vidal-Puig A, Zorzano A, Langin D, Fajas L. CXC ligand 5 is an adipose-tissue derived factor that links obesity to insulin resistance. Cell Metab. 2009;9(4):339–49. · DOI · Paper page
  121. Neels JG, Badeanlou L, Hester KD, Samad F. Keratinocyte-derived chemokine in obesity: expression, regulation, and role in adipose macrophage infiltration and glucose homeostasis. J Biol Chem. 2009;284(31):20692–8. · DOI
  122. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, Gorgun CZ, Hotamisligil GS. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006;313(5790):1137–40. · DOI · Paper page
  123. Aroda VR, Henry RR. Thiazolidinediones: potential link between insulin resistance and cardiovascular disease. Diabetes Spectr. 2003;16(2):120–5. · DOI
  124. Lebovitz HE, Banerji MA. Insulin resistance and its treatment by thiazolidinediones. Recent Prog Horm Res. 2001;56:265–94. · DOI · Paper page

Cited by

See all 671

Metadata

Authors
Rehman, K., & Akash, M. S. H.
Venue
Journal of Biomedical Science
Publisher
Springer Science and Business Media LLC
Published
2016-12
Volume
23
Issue
1
Pages
87-87
ISSN
  • 1021-7770 (ISSN-L)
  • 1423-0127
DOI
10.1186/s12929-016-0303-y
OpenAlex
W2558605920
Cited by
671
References
45
FWCI
25.35
Type
journal article
Language
en
Open access
diamond
Funders
Higher Education Commission, Pakistan (21-1061/SRGP/R&D/HEC/2016)

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This page
CoChat. (2026). Citation check: Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked? https://app.cochat.ai/papers/10.1186/s12929-016-0303-y
The paper
Rehman, K., & Akash, M. S. H. (2016). Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked? Journal of Biomedical Science. https://doi.org/10.1186/s12929-016-0303-y

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.