Mechanisms Linking Inflammation to Insulin Resistance

International Journal of Endocrinology

Volumn 2015, Issue , 2015, Pages

  Chen, Li ^a,b   Chen, Rui ^c   Wang, Hua ^a,b   Liang, Fengxia ^a,b  

^a HUBEI UNIVERSITY OF CHINESE MEDICINE   (China)

^b Hubei Provincial Collaborative Innovation Center   (China)

^c HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPONECTIN; C REACTIVE PROTEIN; CYTOKINE; I KAPPA B KINASE BETA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLAMMASOME; INTERLEUKIN 1BETA; INTERLEUKIN 6; JANUS KINASE; LEPTIN; MONOCYTE CHEMOTACTIC PROTEIN 1; RESISTIN; STAT PROTEIN; STRESS ACTIVATED PROTEIN KINASE; TRANSCRIPTION FACTOR AP 1; TUMOR NECROSIS FACTOR ALPHA;

APOPTOSIS; CELL DIFFERENTIATION; CELL INFILTRATION; CELL PROLIFERATION; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DRUG TARGETING; HUMAN; INFLAMMATION; INSULIN RESISTANCE; MACROPHAGE; MOLECULAR MECHANICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION;

EID: 84934343239     PISSN: 16878337     EISSN: 16878345     Source Type: Journal    
DOI: 10.1155/2015/508409     Document Type: Review

References (89)

1. A. Chawla, K. D. Nguyen, and Y. P. S. Goh, "Macrophagemediated inflammation in metabolic disease", Nature Reviews Immunology, vol. 11, no. 11, pp. 738-749, 2011.
2. F. X. Liang and D. Koya, "Acupuncture: is it effective for treatment of Insulin resistance?" Diabetes, Obesity and Metabolism, vol. 12, no. 7, pp. 555-569, 2010.
3. M. Laakso and J. Kuusisto, "Insulin resistance and hyperglycaemia in cardiovascular disease development", Nature Reviews Endocrinology, vol. 10, no. 5, pp. 293-302, 2014.
4. A. N. Mavrogiannaki and I. N. Migdalis, "Nonalcoholic fatty liver disease, diabetes mellitus and cardiovascular disease: newer data", International Journal of Endocrinology, vol. 2013, Article ID 450639, 8 pages, 2013.
5. M. Gaggini, M. Morelli, E. Buzzigoli, R. A. De Fronzo, E. Bugianesi, and A. Gastaldelli, "Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease", Nutrients, vol. 5, no. 5, pp. 1544-1560, 2013.
6. T. Karlas, J. Wiegand, and T. Berg, "Gastrointestinal complications of obesity: non-alcoholic fatty liver disease (NAFLD) and its sequelae", Best Practice and Research: Clinical Endocrinology and Metabolism, vol. 27, no. 2, pp. 195-208, 2013.
7. M. A. Abdul-Ghani and R. A. De Fronzo, "Pathogenesis of insulin resistance in skeletalmuscle", Journal of Biomedicine and Biotechnology, vol. 2010, Article ID 476279, 19 pages, 2010.
8. J. Ahn, H. Lee, S. W. Im, C. H. Jung, and T. Y. Ha, "Allyl isothiocyanate ameliorates insulin resistance through the regulation of mitochondrial function", The Journal of Nutritional Biochemistry, vol. 25, no. 10, pp. 1026-1034, 2014.
9. D. M. J. Muris, A. J. H. M. Houben, M. T. Schram, and C. D. A. Stehouwer, "Microvascular dysfunction: an emerging pathway in the pathogenesis of obesity-related insulin resistance", Reviews in Endocrine and Metabolic Disorders, vol. 14, no. 1, pp. 29-38, 2013.
10. Ü. Karaca, M. T. Schram, A. J. H. M. Houben, D. M. J. Muris, and C. D. A. Stehouwer, "Microvascular dysfunction as a link between obesity, insulin resistance and hypertension", Diabetes Research and Clinical Practice, vol. 103, no. 3, pp. 382-387, 2014.
11. S. E. Shoelson, J. Lee, and A. B. Goldfine, "Inflammation and insulin resistance", The Journal of Clinical Investigation, vol. 116, no. 7, pp. 1793-1801, 2006.
12. A. C. Könner and J. C. Brüning, "Toll-like receptors: linking inflammation to metabolism", Trends in Endocrinology and Metabolism, vol. 22, no. 1, pp. 16-23, 2011.
13. D. S. Cai, "Neuroinflammation and neurodegeneration in overnutrition-induced diseases", Trends in Endocrinology and Metabolism, vol. 24, no. 1, pp. 40-47, 2013.
14. L. Mohanraj, H.-S. Kim, W. Li et al., "IGFBP-3 inhibits cytokineinduced insulin resistance and early manifestations of atherosclerosis", PLoS ONE, vol. 8, no. 1, Article IDe55084, 2013.
15. G. Daniele, R. G. Mendoza, D. Winnier et al., "The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus", Acta Diabetologica, vol. 51, no. 1, pp. 123-131, 2014.
16. O. Osborn and J. M. Olefsky, "The cellular and signaling networks linking the immune system and metabolism in disease", Nature Medicine, vol. 18, no. 3, pp. 363-374, 2012.
17. C. Martins, L. Aires, I. F. Júnior et al., "Physical activity is related to fatty liver marker in obese youth, independently of central obesity or cardiorespiratory fitness", Journal of Sports Science and Medicine, vol. 14, no. 1, pp. 103-109, 2015.
18. P. Ramadori, D. Kroy, and K. L. Streetz, "Immunoregulation by lipids during the development of non-alcoholic steatohepatitis", Hepatobiliary Surgery and Nutrition, vol. 4, no. 1, pp. 11-23, 2015.
19. M. Sharma, N. K. Vikram, A. Misra et al., "Assessment of 11-β hydroxysteroid dehydrogenase (11-βHSD1) 4478T>G and tumor necrosis factor-α (TNF-α)-308 G>A polymorphisms with obesity and insulin resistance in Asian Indians in North India", Molecular Biology Reports, vol. 40, no. 11, pp. 6261-6270, 2013.
20. B.-C. Lee and J. Lee, "Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance", Biochimica et Biophysica Acta-Molecular Basis of Disease, vol. 1842, no. 3, pp. 446-462, 2014.
21. G. S. Hotamisligil, "Molecularmechanisms of insulin resistance and the role of the adipocyte", International Journal of Obesity and Related Metabolic Disorders, vol. 24, no. 4, pp. S23-S27, 2000.
22. S. E. Kahn, R. L. Hull, and K. M. Utzschneider, "Mechanisms linking obesity to insulin resistance and type 2 diabetes", Nature, vol. 444, no. 7121, pp. 840-846, 2006.
23. X. Zhou and S. You, "Rosiglitazone inhibits hepatic insulin resistance induced by chronic pancreatitis and IKK-β/NF-κB expression in liver", Pancreas, vol. 43, no. 8, pp. 1291-1298, 2014.
24. S. Fernández-Veledo, R. Vila-Bedmar, I. Nieto-Vazquez, and M. Lorenzo, "c-Jun. N-terminal kinase 1/2 activation by tumor necrosis factor-α induces insulin resistance in human visceral but not subcutaneous adipocytes: reversal by liver X receptor agonists", Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 9, pp. 3583-3593, 2009.
25. A. Vázquez-Carballo, V. Ceperuelo-Mallafré, M. R. Chacón et al., "TWEAK prevents TNF-α-induced insulin resistance through PP2A activation in human adipocytes", American Journal of Physiology: Endocrinology and Metabolism, vol. 305, no. 1, pp. E101-E112, 2013.
26. S. M. El-Haggar and T. M. Mostafa, "Adipokines and biochemical changes in Egyptian obese subjects: possible variation with sex and degree of obesity", Endocrine, vol. 48, no. 3, pp. 878-885, 2015.
27. D. Su, G. M. Coudriet, D. H. Kim et al., "Fox O1 links insulin resistance to proinflammatory cytokine IL-1β production in macrophages", Diabetes, vol. 58, no. 11, pp. 2624-2633, 2009.
28. M. Böni-Schnetzler and M. Y. Donath, "Howbiologics targeting the IL-1 system are being considered for the treatment of type 2 diabetes", British Journal of Clinical Pharmacology, vol. 76, no. 2, pp. 263-268, 2013.
29. T. B. Koenen, R. Stienstra, L. J. van Tits et al., "Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1β transcription in human adipose tissue", Diabetes, vol. 60, no. 2, pp. 517-524, 2011.
30. R. W. Grant and V. D. Dixit, "Mechanisms of disease: inflammasome activation and the development of type 2 diabetes", Frontiers in Immunology, vol. 4, article 50, 2013.
31. A. L. Hardaway and I. Podgorski, "IL-1β, RAGE and FABP4: targeting the dynamic trio in metabolic inflammation and related pathologies", Future Medicinal Chemistry, vol. 5, no. 10, pp. 1089-1108, 2013.
32. L. Lukic, N. M. Lalic, N. Rajkovic et al., "Hypertension in obese type 2 diabetes patients is associated with increases in insulin resistance and IL-6 cytokine levels: potential targets for an efficient preventive intervention", International Journal of Environmental Research and Public Health, vol. 11, no. 4, pp. 3586-3598, 2014.
33. L. Serrano-Marco, E. Barroso, I. El Kochairi et al., "The peroxisome proliferator-activated receptor (PPAR) β/δ agonist GW501516 inhibits IL-6-induced signal transducer and activator of transcription 3 (STAT3) activation and insulin resistance in human liver cells", Diabetologia, vol. 55, no. 3, pp. 743-751, 2012.
34. T. Kawaguchi, N. Shiba, T. Maeda et al., "Hybrid training of voluntary and electrical muscle contractions reduces steatosis, insulin resistance, and IL-6 levels in patients with NAFLD: a pilot study", Journal of Gastroenterology, vol. 46, no. 6, pp. 746-757, 2011.
35. L. Dou, T. Zhao, L. Wang et al., "Mi R-200s contribute to interleukin-6 (IL-6)-induced insulin resistance in hepatocytes", The Journal of Biological Chemistry, vol. 288, no. 31, pp. 22596-22606, 2013.
36. J. Yin, Z. Hao, Y. Ma et al., "Concomitant activation of the PI3K/Akt and ERK1/2 signalling is involved in cyclic compressive force-induced IL-6 secretion in MLO-Y4 cells", Cell Biology International, vol. 38, no. 5, pp. 591-598, 2014.
37. T. H. Kim, S. E. Choi, E. S. Ha et al., "IL-6 induction of TLR-4 gene expression via STAT3 has an effect on insulin resistance in human skeletal muscle", Acta Diabetologica, vol. 50, no. 2, pp. 189-200, 2013.
38. J. A. Pedroso, D. C. Buonfiglio, L. I. Cardinali et al., "Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity", Molecular Metabolism, vol. 3, no. 6, pp. 608-618, 2014.
39. A. Stofkova, "Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity", Endocrine Regulations, vol. 43, no. 4, pp. 157-168, 2009.
40. C. L. van der Wijden, H. A. Delemarre-van de Waal, W. van Mechelen, and M. N. van Poppel, "The relationship between moderate-to-vigorous intensity physical activity and insulin resistance, insulin-like growth factor (IGF-1)-system 1, leptin and weight change in healthy women during pregnancy and after delivery", Clinical Endocrinology, vol. 82, no. 1, pp. 68-75, 2015.
41. T.-N. Wang, W.-T. Chang, Y.-W. Chiu et al., "Relationships between changes in leptin and insulin resistance levels in obese individuals following weight loss", Kaohsiung Journal of Medical Sciences, vol. 29, no. 8, pp. 436-443, 2013.
42. A. Yadav, M. A. Kataria, and V. Saini, "Role of leptin and adiponectin in insulin resistance", Clinica Chimica Acta, vol. 417, pp. 80-84, 2013.
43. J. M. Walsh, J. Byrne, R. M. Mahony, M. E. Foley, and F. M. McAuliffe, "Leptin, fetal growth and insulin resistance in nondiabetic pregnancies", Early Human Development, vol. 90, no. 6, pp. 271-274, 2014.
44. I. Jialal, B. Adams-Huet, F. Duong, and G. Smith, "Relationship between retinol-binding protein-4/adiponectin and leptin/adiponectin ratios with insulin resistance and inflammation", Metabolic Syndrome and Related Disorders, vol. 12, no. 4, pp. 227-230, 2014.
45. Y. Toyoshima, O. Gavrilova, S. Yakar et al., "Leptin improves insulin resistance and hyperglycemia in a mouse model of type 2 diabetes", Endocrinology, vol. 146, no. 9, pp. 4024-4035, 2005.
46. S. W. Yau, B. A. Henry, V. C. Russo et al., "Leptin enhances insulin sensitivity by direct and sympathetic nervous system regulation ofmuscle IGFBP-2 expression: evidence fromnonrodent models", Endocrinology, vol. 155, no. 6, pp. 2133-2143, 2014.
47. M. Passos and M. Gonçalves, "Regulation of insulin sensitivity by adiponectin and its receptors in response to physical exercise", Hormone and Metabolic Research, vol. 46, no. 09, pp. 603-608, 2014.
48. T. Yamauchi, Y. Nio, T. Maki et al., "Targeted disruption of Adipo R1 and Adipo R2 causes abrogation of adiponectin binding and metabolic actions", Nature Medicine, vol. 13, no. 3, pp. 332-339, 2007.
49. N. A. Crimmins and L. J. Martin, "Polymorphisms in adiponectin receptor genes ADIPOR1 and ADIPOR2 and insulin resistance", Obesity Reviews, vol. 8, no. 5, pp. 419-423, 2007.
50. V. J. Bermúdez, E. Rojas, A. Toledo et al., "Single-nucleotide polymorphisms in adiponectin, Adipo R1, and Adipo R2 genes: insulin resistance and type 2 diabetesmellitus candidate genes", American Journal of Therapeutics, vol. 20, no. 4, pp. 414-421, 2013.
51. M. P. Reilly, M. Lehrke, M. L. Wolfe, A. Rohatgi, M. A. Lazar, and D. J. Rader, "Resistin is an inflammatory marker of atherosclerosis in humans", Circulation, vol. 111, no. 7, pp. 932-939, 2005.
52. M. Szulinska, K. Musialik, J. Suliburska, I. Lis, and P. Bogdanski, "The effect of L-arginine supplementation on serum resistin concentration in insulin resistance in animal models", European Review for Medical and Pharmacological Sciences, vol. 18, no. 4, pp. 575-580, 2014.
53. Y. Benomar, A. Gertler, P. De Lacy et al., "Central resistin overexposure induces insulin resistance through toll-like receptor 4", Diabetes, vol. 62, no. 1, pp. 102-144, 2013.
54. H. Kanda, S. Tateya, Y. Tamori et al., "MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity", Journal of Clinical Investigation, vol. 116, no. 6, pp. 1494-1505, 2006.
55. K. Kouyama, K. Miyake, M. Zenibayashi et al., "Association of serum MCP-1 concentration and MCP-1 polymorphism with insulin resistance in Japanese individuals with obese type 2 diabetes", Kobe Journal of Medical Sciences, vol. 53, no. 6, pp. 345-354, 2007.
56. Y. Nio, T. Yamauchi, M. Iwabu et al., "Monocyte chemoattractant protein-1 (MCP-1) deficiency enhances alternatively activated M2 macrophages and ameliorates insulin resistance and fatty liver in lipoatrophic diabetic A-ZIP transgenic mice", Diabetologia, vol. 55, no. 12, pp. 3350-3358, 2012.
57. S. P. Weisberg, D. Hunter, R. Huber et al., "CCR2 modulates inflammatory andmetabolic effects of high-fat feeding", Journal of Clinical Investigation, vol. 116, no. 1, pp. 115-124, 2006.
58. M. M. Rahman and G. McFadden, "Modulation of NF-κB signalling by microbial pathogens", Nature Reviews Microbiology, vol. 9, no. 4, pp. 291-306, 2011.
59. H. Sakurai, S. Suzuki, N. Kawasaki et al., "Tumor necrosis factor-α-induced IKK phosphorylation of NF-κB p65 on serine 536 is mediated through the TRAF2, TRAF5, and TAK1 signaling pathway", The Journal of Biological Chemistry, vol. 278, no. 38, pp. 36916-36923, 2003.
60. P. Jiao, J. Ma, B. Feng et al., "FFA-induced adipocyte inflammation and insulin resistance: involvement of ER stress and IKKβ pathways", Obesity, vol. 19, no. 3, pp. 483-491, 2011.
61. M. C. Arkan, A. L. Hevener, F. R. Greten et al., "IKK-β links inflammation to obesity-induced insulin resistance", Nature Medicine, vol. 11, no. 2, pp. 191-198, 2005.
62. S. K. Yekollu, R. Thomas, and B. O'Sullivan, "Targeting curcusomes to inflammatory dendritic cells inhibits NF-κB and improves insulin resistance in obese mice", Diabetes, vol. 60, no. 11, pp. 2928-2938, 2011.
63. M.-Y. Lee, J.-E. Yuk, O.-K. Kwon, S.-R. Oh, H.-K. Lee, and K.-S. Ahn, "Zuonin B inhibits lipopolysaccharide-induced inflammation via downregulation of the ERK1/2 and JNK pathways in RAW264.7 macrophages", Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID728196, 8 pages, 2012.
64. M. S. Han, D. Y. Jung, C. Morel et al., "JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation", Science, vol. 339, no. 6116, pp. 218-222, 2013.
65. M. Pal, C. M. Wunderlich, G. Spohn, H. S. Brönneke, M. Schmidt-Supprian, and F. T. Wunderlich, "Alteration of JNK-1 signaling in skeletal muscle fails to affect glucose homeostasis and obesity-associated insulin resistance in mice", PLoS ONE, vol. 8, no. 1, Article IDe54247, 2013.
66. Y. Nakatani, H. Kaneto, D. Kawamori et al., "Modulation of the JNK pathway in liver affects insulin resistance status", The Journal of Biological Chemistry, vol. 279, no. 44, pp. 45803-45809, 2004.
67. J. Lanuza-Masdeu, M. Isabel Arévalo, C. Vila, A. Barberà, R. Gomis, and C. Caelles, "In vivo jnk activation in pancreatic β-cells leads to glucose intolerance caused by insulin resistance in pancreas", Diabetes, vol. 62, no. 7, pp. 2308-2317, 2013.
68. X. Wu, Y. Mi, H. Yang, A. Hu, Q. Zhang, and C. Shang, "The activation of HMGB1 as a progression factor on inflammation response in normal human bronchial epithelial cells through RAGE/JNK/NF-κB pathway", Molecular and Cellular Biochemistry, vol. 380, no. 1-2, pp. 249-257, 2013.
69. W.-H. Hsu, B.-H. Lee, T.-H. Liao, Y.-W. Hsu, and T.-M. Pan, "Monascus-fermentedmetabolitemonascin suppresses inflammation via PPAR-γ regulation and JNK inactivation in THP-1 monocytes", Food and Chemical Toxicology, vol. 50, no. 5, pp. 1178-1186, 2012.
70. S.-M. Jin, K. S. Kim, S.-Y. Lee et al., "Thesequential combination of a JNK inhibitor and simvastatin protects porcine islets from peritransplant apoptosis and inflammation", Cell Transplantation, vol. 20, no. 7, pp. 1139-1151, 2011.
71. G. Sabio, J. Cavanagh-Kyros, H. J. Ko et al., "Prevention of steatosis by hepatic JNK1", Cell Metabolism, vol. 10, no. 6, pp. 491-498, 2009.
72. F. R. Santos, M. K. Diamond-Stanic, M. Prasannarong, and E. J. Henriksen, "Contribution of the serine kinase c-Jun. N-terminal kinase (JNK) to oxidant-induced insulin resistance in isolated rat skeletalmuscle", Archives of Physiology and Biochemistry, vol. 118, no. 5, pp. 231-236, 2012.
73. H. Miao, J. Ou, Y. Ma et al., "Macrophage CGI-58 deficiency activates ros-inflammasome pathway to promote insulin resistance in mice", Cell Reports, vol. 7, no. 1, pp. 223-235, 2014.
74. B. Vandanmagsar, Y. H. Youm, A. Ravussin et al., "The NALP3/NLRP3 inflammasome instigates obesity-induced autoinflammation and insulin resistance", Nature Medicine, vol. 17, no. 2, pp. 179-188, 2011.
75. R. Stienstra, L. A. B. Joosten, T. Koenen et al., "The inflammasomemediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity", Cell Metabolism, vol. 12, no. 6, pp. 593-605, 2010.
76. R. Stienstra, J. A. Van Diepen, C. J. Tack et al., "Inflammasome is a central player in the induction of obesity and insulin resistance", Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 37, pp. 15324-15329, 2011.
77. S. Fujisaka, I. Usui, A. Bukhari et al., "Regulatorymechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice", Diabetes, vol. 58, no. 11, pp. 2574-2582, 2009.
78. C. N. Lumeng, J. L. Bodzin, and A. R. Saltiel, "Obesity induces a phenotypic switch in adipose tissue macrophage polarization", The Journal of Clinical Investigation, vol. 117, no. 1, pp. 175-184, 2007.
79. D. Spruijt-Metz, B. Adar Emken, M. R. Spruijt et al., "CRP is related to higher leptin levels in minority peripubertal females regardless of adiposity levels", Obesity, vol. 20, no. 3, pp. 512-516, 2012.
80. O. Hanyu, J. Yoshida, E. Abe et al., "High-sensitivity CRP reflects insulin resistance in smokers", Journal of Atherosclerosis and Thrombosis, vol. 16, no. 5, pp. 560-567, 2009.
81. R. Alemzadeh and J. Kichler, "Gender differences in the association of insulin resistance and high-sensitivity c-reactive protein in obese adolescents", Journal of Diabetes & Metabolic Disorders, vol. 13, article 35, 9 pages, 2014.
82. E. J. Brunner, M. Kivimäki, D. R. Witte et al., "Inflammation, insulin resistance, and diabetes-mendelian randomization using CRP haplotypes points upstream", PLoS Medicine, vol. 5, no. 8, pp. 1278-1286, 2008.
83. J.-F. Tanti, F. Ceppo, J. Jager, and F. Berthou, "Implication of inflammatory signaling pathways in obesity-induced insulin resistance", Frontiers in Endocrinology, vol. 3, article 181, Article ID Article 181, 2013.
84. D. Xu, C. Yin, S. Wang, and Y. Xiao, "JAK-STAT in lipidmetabolism of adipocytes", JAK-STAT, vol. 2, no. 4, Article ID e27203, 2014.
85. D. A. Harrison, "The JAK/STAT pathway", Cold Spring Harbor Perspectives in Biology, vol. 4, no. 3, 2012.
86. A. J. Richard and J. M. Stephens, "Emerging roles of JAK-STAT signaling pathways in adipocytes", Trends in Endocrinology & Metabolism, vol. 22, no. 8, pp. 325-332, 2011.
87. B. A. Croker, H. Kiu, and S. E. Nicholson, "SOCS regulation of the JAK/STAT signalling pathway", Seminars in Cell and Developmental Biology, vol. 19, no. 4, pp. 414-422, 2008.
88. H. Kiu and S. E. Nicholson, "Biology and significance of the JAK/STAT signalling pathways", Growth Factors, vol. 30, no. 2, pp. 88-106, 2012.
89. W. X. Li, "Canonical and non-canonical JAK-STAT signaling", Trends in Cell Biology, vol. 18, no. 11, pp. 545-551, 2008.