Inflammatory process in type 2 diabetes: The role of cytokines

Annals of the New York Academy of Sciences

Volumn 1084, Issue , 2006, Pages 89-117

  Alexandraki, Krystallenia ^a   Piperi, Christina ^a   Kalofoutis, Christos ^a   Singh, Jaipaul ^b   Alaveras, Antonis ^a   Kalofoutis, Anastasios ^a  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^b UNIVERSITY OF CENTRAL LANCASHIRE   (United Kingdom)

Author keywords

Cytokines; Inflammation; Type 2 diabetes mellitus

Indexed keywords

ADIPONECTIN; ANTILIPEMIC AGENT; CANDESARTAN; CYTOKINE; ENDOTHELIN 1; GAMMA INTERFERON; GLITAZONE DERIVATIVE; INTERLEUKIN 1BETA; INTERLEUKIN 6; LEPTIN; LOSARTAN; METFORMIN; MONOCYTE CHEMOTACTIC PROTEIN 1; PIOGLITAZONE; PLACEBO; PRAVASTATIN; RAMIPRIL; RESISTIN; ROSIGLITAZONE; SIMVASTATIN; TEMOCAPRIL; TROGLITAZONE; TUMOR NECROSIS FACTOR ALPHA; VASCULAR CELL ADHESION MOLECULE 1;

ADIPOCYTE; ADIPOSE TISSUE; APOPTOSIS; BODY MASS; CELL FUNCTION; CLINICAL TRIAL; CONFERENCE PAPER; DIET THERAPY; EXERCISE; HELPER CELL; HUMAN; HYPERTENSION; IN VITRO STUDY; INFLAMMATION; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN SENSITIVITY; LIVER CELL; MACROPHAGE; MONONUCLEAR CELL; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS ISLET BETA CELL; WEIGHT REDUCTION; ANIMAL; EXPERIMENTAL DIABETES MELLITUS; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW;

ANIMALS; CYTOKINES; DIABETES MELLITUS, EXPERIMENTAL; DIABETES MELLITUS, TYPE 2; HUMANS; INFLAMMATION;

EID: 34247604351     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1196/annals.1372.039     Document Type: Conference Paper

References (285)

1. PICKUP, J.C. & M.A. CROOK. 1998. Is type II diabetes mellitus a disease of the innate immune system? Diabetologia 41: 1241-1248.
2. GABAY, C. & I. KUSHNER. 1999. Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med. 340: 448-454.
3. BLAKE, G.J. & P.M. RIDKER. 2002. Inflammatory bio-arkers and cardiovascular risk prediction. J. Intern. Med. 252: 283-294.
4. TORRES, J.L. & P.M. RIDKER. 2003. Clinical use of high sensitivity C-reactive protein for the prediction of adverse cardiovascular events. Curr. Opin. Cardiol. 18: 471-478.
5. PICKUP, J.C. 2004. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 27: 813-823.
6. TRACY, R.P. Diabetes and atherothrombotic disease: linked through inflammation? Semin. Vasc. Med. 2: 67-73.
7. FERRONI, P. et al. 2004. Inflammation, insulin resistance, and obesity. Curr. Atheroscler. Rep. 6: 424-431.
8. PEARSON, T.A. et al. 2003. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107: 499-511.
9. CHEN, H. 2006. Cellular inflammatory responses: novel insights for obesity and insulin resistance. Pharmacol. Res. 53: 469-477.
10. DANDONA, P., A. ALJADA & A. BANDYOPADHYAY. 2004. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 25: 4-7.
11. DANDONA, P. et al. 2003. The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis-related complications in type 2 diabetes. J. Clin. Endocrinol. Metab. 88: 2422-2429.
12. BIONDI-ZOCCAI, G.G. et al. 2003. Atherothrombosis, inflammation, and diabetes. J. Am. Coll. Cardiol. 41: 1071-1077.
13. BLOOMGARDEN, Z.T. 2003. Inflammation and insulin resistance. Diabetes Care 26: 1922-1926.
14. PITTAS, A.G., N.A. JOSEPH & A.S. GREENBERG. 2004. Adipocytokines and insulin resistance. J. Clin. Endocrinol. Metab. 89: 447-452.
15. FERNANDEZ-REAL, J.M. & W. RICART. 2003. Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr. Rev. 24: 278-301.
16. PRADHAN, A.D. & P.M. RIDKER. 2002. Do atherosclerosis and type 2 diabetes share a common inflammatory basis? Eur. Heart J. 23: 831-834.
17. HAN, T.S. et al. 2002. Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study. Diabetes Care 25: 2016-2021.
18. DUNCAN, B.B. et al. Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes 52: 1799-1805.
19. PRADHAN, A.D. et al. 2003. C-reactive protein is independently associated with fasting insulin in nondiabetic women. Arterioscler. Thromb. Vasc. Biol. 23: 650-655.
20. PRADHAN, A.D. et al. 2001. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286: 327-334.
21. FREEMAN, D.J. et al. 2002. C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes 51: 1596-1600.
22. FESTA, A. et al. 2000. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 102: 42-47.
23. FESTA, A. et al. 2002. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51: 1131-1137.
24. ENGELGAU, M.M. et al. 2004. Prevention of type 2 diabetes: issues and strategies for identifying persons for interventions. Diabetes Technol.Ther. 6: 874-882.
25. LEAHY, J.L. 2005. Pathogenesis of type 2 diabetes mellitus. Arch. Med. Res. 36: 197-209.
26. ROTTER, V., I. NAGAEV & U. SMITH. 2003. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factoralpha, overexpressed in human fat cells from insulin-resistant subjects. J. Biol. Chem. 278: 45777-45784.
27. HIROSUMI, J. et al. 2002. A central role for JNK in obesity and insulin resistance. Nature 420: 333-336.
28. YUAN, M. et al. 2001. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293: 1673-1677.
29. KIM, J.A., K.K. KOH & M.J. QUON. 2005. The union of vascular and metabolic actions of insulin in sickness and in health. Arterioscler. Thromb. Vasc. Biol. 25: 889-891.
30. STERN, M.P. 1995. Diabetes and cardiovascular disease. The "common soil" hypothesis. Diabetes 44: 369-374.
31. BAYS, H., L. MANDARINO & R.A. DEFRONZO. 2004. 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. J. Clin. Endocrinol. Metab. 89: 463-478.
32. YUDKIN, J.S. et al. 2000. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 148: 209-214.
33. YUDKIN, J.S. et al. 1999. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler. Thromb. Vasc. Biol. 19: 972-978.
34. HAK, A.E. et al. 1999. Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women. Arterioscler. Thromb. Vasc. Biol. 19: 1986-1991.
35. HANSSON, G.K. et al. 1989. Immune mechanisms in atherosclerosis. Arteriosclerosis 9: 567-578.
36. PICKUP, J.C. et al. 1997. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 40: 1286-1292.
37. HOEKSTRA, T. et al. 2005. Relationship of C-reactive protein with components of the metabolic syndrome in normal-weight and overweight elderly. Nutr. Metab. Cardiovasc. Dis. 15: 270-278.
38. DUNCAN, B.B. & M.I. SCHMIDT. Chronic activation of the innate immune system may underlie the metabolic syndrome. Sao Paulo Med. J. 119: 122-127.
39. SCHMIDT, M.I. & B.B. DUNCAN. 2003. Diabesity: an inflammatory metabolic condition. Clin. Chem. Lab. Med. 41: 1120-1130.
40. BUTLER, A.E. et al. 2003. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52: 102-110.
41. KOLB, H. & T. MANDRUP-POULSEN. 2005. An immune origin of type 2 diabetes? Diabetologia 48: 1038-1050.
42. DONATH, M.Y. et al. 1999. Hyperglycemia-induced beta-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes 48: 738-744.
43. BELLONE, M. et al. 1997. Processing of engulfed apoptotic bodies yields T cell epitopes. J. Immunol. 159: 5391-5399.
44. TRUDEAU, J.D. et al. 2000. Neonatal beta-cell apoptosis: a trigger for autoimmune diabetes? Diabetes 49: 1-7.
45. MAEDLER, K. et al. 2002. Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J. Clin. Invest. 110: 851-860.
46. MAEDLER, K. et al. 2001. Glucose induces beta-cell apoptosis via upregulation of the Fas receptor in human islets. Diabetes 50: 1683-1690.
47. FRAYN, K.N. et al. 2003. Integrative physiology of human adipose tissue. Int. J. Obes. Relat. Metab. Disord. 27: 875-888.
48. FRIED, S.K., D.A. BUNKIN & A.S. GREENBERG. 1998. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J. Clin. Endocrinol. Metab. 83: 847-850.
49. HOTAMISLIGIL, G.S., N.S. SHARGILL & B.M. SPIEGELMAN. 1993. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259: 87-91.
50. MEIER, C.A. et al. 2002. IL-1 receptor antagonist serum levels are increased in human obesity: a possible link to the resistance to leptin? J. Clin. Endocrinol. Metab. 87: 1184-1188.
51. ZHANG, Y. et al. 1994. Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425-432.
52. WEISBERG, S.P. et al. 2003. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112: 1796-1808.
53. XU, H. et al. 2003. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112: 1821-1830.
54. GHANIM, H. et al. 2004. Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation 110: 1564-1571.
55. DANDONA, P. et al. 2005. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 111: 1448-1454.
56. WELLEN, K.E. & G.S. HOTAMISLIGIL. Inflammation, stress, and diabetes. J. Clin. Invest. 115: 1111-1119.
57. CHARRIERE, G. et al. 2003. Preadipocyte conversion to macrophage. Evidence of plasticity. J. Biol. Chem. 278: 9850-9855.
58. CHRISTIANSEN, T., B. RICHELSEN & J.M. BRUUN. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int. J. Obes. (Lond.) 29: 146-150.
59. GERHARDT, C.C. et al. 2001. Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol. Cell. Endocrinol. 175: 81-92.
60. MURDOLO, G. & U. SMITH. 2006. The dysregulated adipose tissue: a connecting link between insulin resistance, type 2 diabetes mellitus and atherosclerosis. Nutr. Metab. Cardiovasc. Dis. 16(Suppl 1): S35-S38.
61. CINTI, S. et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J. Lipid Res. 46: 2347-2355.
62. FUJIWARA, N. & K. KOBAYASHI. 2005. Macrophages in inflammation. Curr. Drug Targets Inflamm. Allergy 4: 281-286.
63. COPPACK, S.W. 2001. Pro-inflammatory cytokines and adipose tissue. Proc. Nutr. Soc. 60: 349-356.
64. ALDHAHI, W. & O. HAMDY. 2003. Adipokines, inflammation, and the endothelium in diabetes. Curr. Diab. Rep. 3: 293-298.
65. KERSHAW, E.E. & J.S. FLIER. 2004. Adipose tissue as an endocrine organ. J. Clin. Endocrinol. Metab. 89: 2548-2556.
66. MATHIS, D., L. VENCE & C. BENOIST. 2001. beta-Cell death during progression to diabetes. Nature 414: 792-798.
67. PIETROPAOLO, M. et al. 2000. Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes. Diabetes 49: 32-38.
68. DONATH, M.Y. et al. Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes. J. Mol. Med. 81: 455-470.
69. GIANNOUKAKIS, N. et al. 1999. Adenoviral gene transfer of the interleukin-1 receptor antagonist protein to human islets prevents IL-1beta-induced beta-cell impairment and activation of islet cell apoptosis in vitro. Diabetes 48: 1730-1736.
70. LOWETH, A.C. et al. 1998. Human islets of Langerhans express Fas ligand and undergo apoptosis in response to interleukin-1beta and Fas ligation. Diabetes 47: 727-732.
71. RABINOVITCH, A. et al. 1990. Cytotoxic effects of cytokines on human pancreatic islet cells in monolayer culture. J. Clin. Endocrinol. Metab. 71: 152-156.
72. STASSI, G. et al. 1997. Nitric oxide primes pancreatic beta cells for Fas-mediated destruction in insulin-dependent diabetes mellitus. J. Exp. Med. 186: 1193-1200.
73. KOH, K.K., S.H. HAN & M.J. QUON. 2005. Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions. J. Am. Coll. Cardiol. 46: 1978-1985.
74. MANDRUP-POULSEN, T. 1996. The role of interleukin-1 in the pathogenesis of IDDM. Diabetologia 39: 1005-1029.
75. EIZIRIK, D.L. & T. MANDRUP-POULSEN. 2001. A choice of death-the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia 44: 2115-2133.
76. MAEDLER, K. et al. 2004. Leptin modulates beta cell expression of IL-1 receptor antagonist and release of IL-1beta in human islets. Proc. Natl. Acad. Sci. USA 101: 8138-8143.
77. MAEDLER, K. et al. 2002. FLIP switches Fas-mediated glucose signaling in human pancreatic beta cells from apoptosis to cell replication. Proc. Natl. Acad. Sci. USA 99: 8236-8241.
78. + channel 6.2 (SUR/Kir6.2) selective potassium channel opener in human islets. Diabetes 53: 1706-1713.
79. AARNES, M., S. SCHONBERG & V. GRILL. 2002. Fatty acids potentiate interleukin-1beta toxicity in the beta-cell line INS-1E. Biochem. Biophys. Res. Commun. 296: 189-193.
80. KIM, J.K. et al. 2001. Prevention of fat-induced insulin resistance by salicylate. J. Clin. Invest. 108: 437-446.
81. HOTAMISLIGIL, G.S. et al. 1995. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J. Clin. Invest. 95: 2409-2415.
82. RUAN, H. & H.F. LODISH. 2003. Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev. 14: 447-455.
83. SENN, J.J. et al. 2003. Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J. Biol. Chem. 278: 13740-13746.
84. PERALDI, P. & B.B. SPIEGELMAN. 1998. TNF-alpha and insulin resistance: summary and future prospects. Mol. Cell. Biochem. 182: 169-175.
85. MOHAMED-ALI, V. et al. 1999. Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo. Am. J. Physiol. 277: E971-E975.
86. ARNER, P. 2001. Regional differences in protein production by human adipose tissue. Biochem. Soc. Trans. 29: 72-75.
87. ZHANG, H.H. et al. 2002. Tumor necrosis factor-alpha stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. Diabetes 51: 2929-2935.
88. MANDRUP-POULSEN, T. 2001. Beta-cell apoptosis: stimuli and signaling. Diabetes 50(Suppl 1): S58-S63.
89. UYSAL, K.T. 1997. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389: 610-614.
90. UYSAL, K.T., S.M. WIESBROCK & G.S. HOTAMISLIGIL. 1998. Functional analysis of tumor necrosis factor (TNF) receptors in TNF-alpha-mediated insulin resistance in genetic obesity. Endocrinology 139: 4832-4838.
91. RASK-MADSEN, C. et al. 2003. Tumor necrosis factor-alpha inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans. Circulation 108: 1815-1821.
92. OFEI, F. et al. 1996. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 45: 881-885.
93. PAQUOT, N. et al. 2000. No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients. J. Clin. Endocrinol. Metab. 85: 1316-1319.
94. DI ROCCO, P. et al. 2004. Lowered tumor necrosis factor receptors, but not increased insulin sensitivity, with infliximab. Obes. Res. 12: 734-739.
95. STEPHENS, J.M. & P.H. PEKALA. 1991. Transcriptional repression of the GLUT4 and C/EBP genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha. J. Biol. Chem. 266: 21839-21845.
96. HOTAMISLIGIL, G.S. et al. 1996. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271: 665-668.
97. ZENG, M. et al. 2002. Tumor necrosis factor-alpha-induced leukocyte adhesion and microvessel permeability. Am. J. Physiol. Heart Circ. Physiol. 283: H2420-H2430.
98. ASHTON, A.W. et al. 2003. Inhibition of tumor necrosis factor alpha-mediated NFkappaB activation and leukocyte adhesion, with enhanced endothelial apoptosis, by G protein-linked receptor (TP) ligands. J. Biol. Chem. 278: 11858-11866.
99. PATEL, J.N. et al. 2002. Effects of tumour necrosis factor-alpha in the human forearm: blood flow and endothelin-1 release. Clin. Sci. (Lond.) 103: 409-415.
100. WEBER, C. et al. 1995. Inhibitors of protein tyrosine kinase suppress TNF-stimulated induction of endothelial cell adhesion molecules. J. Immunol. 155: 445-451.
101. UZUI, H. et al. Increased expression of membrane type 3-matrix metalloproteinase in human atherosclerotic plaque: role of activated macrophages and inflammatory cytokines. Circulation 106: 3024-3030.
102. FARD, A. et al. 2000. Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes. Arterioscler. Thromb. Vasc. Biol. 20: 2039-2044.
103. KATSUKI, A. et al. 1998. Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus. J. Clin. Endocrinol. Metab. 83: 859-862.
104. KAMIMURA, D., K. ISHIHARA & T. HIRANO. 2003. IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev. Physiol. Biochem. Pharmacol. 149: 1-38.
105. JONES, S.A. et al. 2001. The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J. 15: 43-58.
106. SCHELLER, J. et al. 2006. Interleukin-6 trans-signalling in chronic inflammation and cancer. Scand. J. Immunol. 63: 321-329.
107. KRISTIANSEN, O.P. & T. MANDRUP-POULSEN. 2005. Interleukin-6 and diabetes, or the indifferent? Diabetes 54(Suppl 2): S114-S124.
108. WILLERSON, J.T. & P.M. RIDKER. 2004. Inflammation as a cardiovascular risk factor. Circulation 109(Suppl 2): II2-II10.
109. NONOGAKI, K. et al. 1995. Interleukin-6 stimulates hepatic triglyceride secretion in rats. Endocrinology 136: 2143-2149.
110. SOUTHERN, C., D. SCHULSTER & I.C. GREEN. 1990. Inhibition of insulin secretion from rat islets of Langerhans by interleukin-6. An effect distinct from that of interleukin-1. Biochem. J. 272: 243-245.
111. SANDLER, S. et al. 1990. Interleukin-6 affects insulin secretion and glucose metabolism of rat pancreatic islets in vitro. Endocrinology 126: 1288-1294.
112. WADT, K.A. et al. 1998. Ciliary neurotrophic factor potentiates the beta-cell inhibitory effect of IL-1beta in rat pancreatic islets associated with increased nitric oxide synthesis and increased expression of inducible nitric oxide synthase. Diabetes 47: 1602-1608.
113. CHOI, S.E. et al. 2004. IL-6 protects pancreatic islet beta cells from proinflammatory cytokines-induced cell death and functional impairment in vitro and in vivo. Transpl. Immunol. 13: 43-53.
114. CAMPBELL, I.L. et al. 1989. Evidence for IL-6 production by and effects on the pancreatic beta-cell. J. Immunol. 143: 1188-1191.
115. CAREY, A.L. & M.A. FEBBRAIO. 2004. Interleukin-6 and insulin sensitivity: friend or foe? Diabetologia 47: 1135-1142.
116. MOHAMED-ALI, V. et al. 1997. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J. Clin. Endocrinol. Metab. 82: 4196-4200.
117. STOUTHARD, J.M., R.P. OUDE ELFERINK & H.P. SAUERWEIN. Interleukin-6 enhances glucose transport in 3T3-L1 adipocytes. Biochem. Biophys. Res.Commun.220: 241-245.
118. LAGATHU, C. et al. 2003. Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone. Biochem. Biophys. Res. Commun. 311: 372-379.
119. FASSHAUER, M. et al. 2003. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 301: 1045-1050.
120. EMANUELLI, B. et al. 2001. SOCS-3 inhibits insulin signaling and is up-regulated in response to tumor necrosis factor-alpha in the adipose tissue of obese mice. J. Biol. Chem. 276: 47944-47949.
121. SHI, H. et al. 2004. Suppressor of cytokine signaling 3 is a physiological regulator of adipocyte insulin signaling. J. Biol. Chem. 279: 34733-34740.
122. RIEUSSET, J. et al. 2004. Suppressor of cytokine signaling 3 expression and insulin resistance in skeletal muscle of obese and type 2 diabetic patients. Diabetes 53: 2232-2241.
123. KIM, H.J. et al. 2004. Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes 53: 1060-1067.
124. KLOVER, P.J. et al. Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes 52: 2784-2789.
125. KANEMAKI, T. et al. 1998. Interleukin 1beta and interleukin 6, but not tumor necrosis factor alpha, inhibit insulin-stimulated glycogen synthesis in rat hepatocytes. Hepatology 27: 1296-1303.
126. SENN, J.J. et al. 2002. Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes 51: 3391-3399.
127. FEBBRAIO, M.A. et al. 2004. Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction. Diabetes 53: 1643-1648.
128. PEDERSEN, B.K. et al. 2004. The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor? Proc. Nutr. Soc. 63: 263-267.
129. STRASSMANN, G. et al. 1993. The role of interleukin-6 in lipopolysaccharide-induced weight loss, hypoglycemia and fibrinogen production, in vivo. Cytokine 5: 285-290.
130. EIZIRIK, D.L. et al. 1994. Cytokines suppress human islet function irrespective of their effects on nitric oxide generation. J. Clin. Invest. 93: 1968-1974.
131. DICOSMO, B.F., D. PICARELLA & R.A. FLAVELL. 1994. Local production of human IL-6 promotes insulitis but retards the onset of insulin-dependent diabetes mellitus in non-obese diabetic mice. Int. Immunol. 6: 1829-1837.
132. CAMPBELL, I.L. et al. 1994. Islet inflammation and hyperplasia induced by the pancreatic islet-specific overexpression of interleukin-6 in transgenic mice. Am. J. Pathol. 145: 157-166.
133. DI GREGORIO, G.B. et al. Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity. Am. J. Physiol. Endocrinol. Metab. 287: E182-E187.
134. TSIGOS, C. et al. 1997. Dose-dependent effects of recombinant human interleukin-6 on glucose regulation. J. Clin. Endocrinol. Metab. 82: 4167-4170.
135. VAN HALL, G. et al. 2003. Interleukin-6 stimulates lipolysis and fat oxidation in humans. J. Clin. Endocrinol. Metab. 88: 3005-3010.
136. PEDERSEN, M. et al. 2003. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes. Mech. Ageing Dev. 124: 495-502.
137. MOHAMED-ALI, V. et al. 2001. beta-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies. J Clin Endocrinol Metab. 86: 5864-5869.
138. CAREY, A.L. et al. 2004. Interleukin-6 and tumor necrosis factor-alpha are not increased in patients with Type 2 diabetes: evidence that plasma interleukin-6 is related to fat mass and not insulin responsiveness. Diabetologia 47: 1029-1037.
139. BASTARD, J.P. et al. 2002. Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J. Clin. Endocrinol. Metab. 87: 2084-2089.
140. SPRANGER, J. 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: 812-817.
141. HU, F.B. et al. 2004. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 53: 693-700.
142. KAMIMURA, D., K. ISHIHARA & T. HIRANO. 2003. IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev. Physiol. Biochem. Pharmacol. 149: 1-38.
143. WALLENIUS, K., J.O. JANSSON & V. WALLENIUS. 2003. The therapeutic potential of interleukin-6 in treating obesity. Expert Opin. Biol. Ther. 3: 1061-1070.
144. WALLENIUS, V. et al. 2002. Interleukin-6-deficient mice develop mature-onset obesity. Nat. Med. 8: 75-79.
145. MOONEY, R.A. et al. 2001. Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistance. J. Biol. Chem. 276: 25889-25893.
146. UEKI, K., T. KADOWAKI & C.R. KAHN. 2005. Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome. Hepatol. Res. 33: 185-192.
147. MAEDLER, K. et al. Leptin modulates beta cell expression of IL-1 receptor antagonist and release of IL-1beta in human islets. Proc. Natl. Acad. Sci. USA 101: 8138-8143.
148. AHIMA, R.S. & J.S. FLIER. 2000. Leptin. Annu. Rev. Physiol. 62: 413-437.
149. OTERO, M. et al. 2006. Towards a pro-inflammatory and immunomodulatory emerging role of leptin. Rheumatology. (Oxford) 45: 944-950.
150. PEELMAN, F. et al. 2004. Leptin: linking adipocyte metabolism with cardiovascular and autoimmune diseases. Prog. Lipid. Res. 43: 283-301.
151. La CAVA, A., C. ALVIGGI & G. MATARESE. 2004. Unraveling the multiple roles of leptin in inflammation and autoimmunity. J. Mol. Med. 821: 4-11.
152. HUANG, L. & C. LI. Leptin: a multifunctional hormone. Cell. Res. 10: 81-92.
153. NAKATA, M. et al. 1999. Leptin promotes aggregation of human platelets via the long form of its receptor. Diabetes 48: 426-429.
154. AHIMA, R.S. et al. 1996. Role of leptin in the neuroendocrine response to fasting. Nature 382: 250-252.
155. CHAN, J.L. et al. 2003. The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. J. Clin. Invest. 111: 1409-1421.
156. ZHANG, F. et al. 2005. Leptin: structure, function and biology. Vitam. Horm. 71: 345-372.
157. COHEN, B. et al. 1996. Modulation of insulin activities by leptin. Science 274: 1185-1188.
158. SZANTO, I. & C.R. KAHN. 2000. Selective interaction between leptin and insulin signaling pathways in a hepatic cell line. Proc. Natl. Acad. Sci. USA 97: 2355-2360.
159. KIM, Y.B. et al. 2000. In vivo administration of leptin activates signal transduction directly in insulin-sensitive tissues: overlapping but distinct pathways from insulin. Endocrinology 141: 2328-2339.
160. ISLAM, M.S., A. SJOHOLM & V. EMILSSON. 2000. Fetal pancreatic islets express functional leptin receptors and leptin stimulates proliferation of fetal islet cells. Int. J. Obes. Relat. Metab. Disord. 24: 1246-1253.
161. OKUYA, S. et al. 2001. Leptin increases the viability of isolated rat pancreatic islets by suppressing apoptosis. Endocrinology 142: 4827-4830.
162. SHIMABUKURO, M. et al. 1998. Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression. Proc. Natl. Acad. Sci. USA 95: 9558-9561.
163. TANABE, K. et al. 1997. Leptin induces proliferation of pancreatic beta cell line MIN6 through activation of mitogen-activated protein kinase. Biochem. Biophys. Res. Commun. 241: 765-768.
164. MAEDLER, K. & M.Y. DONATH. 2004. Beta-cells in type 2 diabetes: a loss of function and mass. Horm. Res. 3(62 Suppl): 67-73.
165. WANG, J. et al. 2001. Overfeeding rapidly induces leptin and insulin resistance. Diabetes 50: 2786-2791.
166. WABITSCH, M. et al. 1996. Insulin and cortisol promote leptin production in cultured human fat cells. Diabetes 45: 1435-1438.
167. RUSSELL, C.D. et al. 1998. Leptin expression in adipose tissue from obese humans: depot-specific regulation by insulin and dexamethasone. Am. J. Physiol. 275(3 Pt 1): E507-E515.
168. BAI, Y. et al. 1996. Obese gene expression alters the ability of 30A5 preadipocytes to respond to lipogenic hormones. J. Biol. Chem. 271: 13939-13942.
169. MULLER, G. et al. 1997. Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J. Biol. Chem. 272: 10585-10593.
170. REIDY, S.P. & J. WEBER. 2000. Leptin: an essential regulator of lipid metabolism. Comp. Biochem. Physiol. A. Mol. Integr. Physiol. 125: 285-298.
171. SIVITZ, W.I. et al. 1997. Effects of leptin on insulin sensitivity in normal rats. Endocrinology 138: 3395-3401.
172. ROSSETTI, L. et al. 1997. Short term effects of leptin on hepatic gluconeogenesis and in vivo insulin action. J. Biol. Chem. 272: 27758-27763.
173. PELLEYMOUNTER, M.A. et al. 1995. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269: 540-543.
174. CHINOOKOSWONG, N., J.L. WANG & Z.Q. SHI. 1999. Leptin restores euglycemia and normalizes glucose turnover in insulin-deficient diabetes in the rat. Diabetes 48: 1487-1492.
175. SHIMOMURA, I. et al. 1999. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 401: 73-76.
176. UNGER, R.H. 2002. Lipotoxic diseases. Annu. Rev. Med. 53: 319-336.
177. KAMOHARA, S. et al. 1997. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389: 374-377.
178. YEN, T.T. et al. 1977. Dissociation of obesity, hypercholesterolemia and diabetes from atherosclerosis in ob/ob mice. Experientia 33: 995-996.
179. SCHAFER, K. et al. 2004. Leptin promotes vascular remodeling and neointimal growth in mice. Arterioscler. Thromb. Vasc. Biol. 24: 112-117.
180. MATSUMURA, K. et al. 2003. Neural regulation of blood pressure by leptin and the related peptides. Regul. Pept. 114: 79-86.
181. SHEK, E.W., M.W. BRANDS & J.E. HALL. 1998. Chronic leptin infusion increases arterial pressure. Hypertension 31(1 Pt 2): 409-414.
182. LEMBO, G. et al. 2000. Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes 49: 293-297.
183. DUNBAR, J.C., Y. HU & H. LU. 1997. Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes 46: 2040-2043.
184. MATSUMURA, K. et al. 2000. Central effects of leptin on cardiovascular and neurohormonal responses in conscious rabbits. Am. J. Physiol. Regul. Integr. Comp. Physiol. 278: R1314-R1320.
185. AGATA, J. et al. 1997. High plasma immunoreactive leptin level in essential hypertension. Am. J. Hypertens. 10(10 Pt 1): 1171-1174.
186. SIERRA-HONIGMANN, M.R. et al. 1998. Biological action of leptin as an angiogenic factor. Science 281: 1683-1686.
187. PARK, H.Y. et al. Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro. Exp. Mol. Med. 33: 95-102.
188. BODARY, P.F. et al. 2002. Effect of leptin on arterial thrombosis following vascular injury in mice. JAMA 287: 1706-1709.
189. ODA, A., T. TANIGUCHI & M. YOKOYAMA. 2001. Leptin stimulates rat aortic smooth muscle cell proliferation and migration. Kobe J. Med. Sci. 47: 141-150.
190. VAN HEEK, M. et al. 1997. Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J. Clin. Invest. 99: 385-390.
191. BJORBAEK, C. et al. 1998. Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol. Cell. 1: 619-625.
192. BJORBAEK, C. et al. 1999. The role of SOCS-3 in leptin signaling and leptin resistance. J. Biol. Chem. 274: 30059-30065.
193. SODERBERG, S. et al. 1999. Leptin is associated with increased risk of myocardial infarction. J. Intern. Med. 246: 409-418.
194. WALLACE, A.M. et al. 2001. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation 104: 3052-3056.
195. SODERBERG, S. et al. 1999. Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort. Stroke 30: 328-337.
196. ZIMMET, P. et al. 1999. Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players. Ann. N. Y. Acad. Sci. 892: 25-44.
197. DE COURTEN, M. et al. 1997. Hyperleptinaemia: the missing link in the, metabolic syndrome? Diabet. Med. 14: 200-208.
198. CICCONE, M. et al. 2001. Plasma leptin is independently associated with the intima-media thickness of the common carotid artery. Int. J. Obes. Relat. Metab. Disord. 25: 805-810.
199. SINGHAL, A. et al. 2002. Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease? Circulation 106: 1919-1924.
200. CAMMISOTTO, P.G. et al. 2005. Regulation of leptin secretion from white adipocytes by insulin, glycolytic substrates, and amino acids. Am. J. Physiol. Endocrinol. Metab. 289: E166-E171.
201. FLIERS, E. et al. 2003. White adipose tissue: getting nervous. J. Neuroendocrinol. 15: 1005-1010.
202. BODEN, G. et al. 1997. Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects. J. Clin. Invest. 100: 1107-1113.
203. ZAKRZEWSKA, K.E. et al. 1997. Glucocorticoids as counterregulatory hormones of leptin: toward an understanding of leptin resistance. Diabetes 46: 717-719.
204. JIN, L. et al. 199. Leptin and leptin receptor expression in normal and neoplastic human pituitary: evidence of a regulatory role for leptin on pituitary cell proliferation. J. Clin. Endocrinol. Metab. 84: 2903-2911.
205. HEIMAN, M.L. et al. 1997. Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. Endocrinology 138: 3859-3863.
206. KRUSE, M. et al. 1998. Leptin down-regulates the steroid producing system in the adrenal. Endocr. Res. 24: 587-590.
207. WABITSCH, M. et al. 1996. Insulin and cortisol promote leptin production in cultured human fat cells. Diabetes 45: 1435-1438.
208. DE VOS, P. et al. 1995. Induction of ob gene expression by corticosteroids is accompanied by body weight loss and reduced food intake. J. Biol. Chem. 270: 15958-15961.
209. OZATA, M. I.C. OZDEMIR & J. LICINIO. 1999. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J. Clin. Endocrinol. Metab. 84: 3686-3695.
210. SARRAF, P. et al. 1997. Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J. Exp. Med. 185: 171-175.
211. OTERO, M. et al. 2005. Leptin, from fat to inflammation: old questions and new insights. FEBS Lett. 579: 295-301.
212. GUALILLO, O. et al. 2000. Elevated serum leptin concentrations induced by experimental acute inflammation. Life Sci. 67: 2433-2441.
213. POPA, C. et al. 2005. Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis. Ann. Rheum. Dis. 64: 1195-1198.
214. ZHANG, H.H. et al. 2000. Tumour necrosis factor-alpha exerts dual effects on human adipose leptin synthesis and release. Mol. Cell. Endocrinol. 159: 79-88.
215. FAGGIONI, R., K.R. FEINGOLD & C. GRUNFELD. 2001. Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J. 15: 2565-2571.
216. SANNA, V. et al. 2003. Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses. J. Clin. Invest. 111: 241-250.
217. KIMURA, M. et al. 1998. T lymphopenia in obese diabetic (db/db) mice is nonselective and thymus independent. Life Sci. 62: 1243-1250.
218. LA CAVA, A. & G. MATARESE. 2004. The weight of leptin in immunity. Nat. Rev. Immunol. 4: 371-379.
219. MATARESE, G., S. MOSCHOS & C.S. MANTZOROS. 2005. Leptin in immunology. J. Immunol. 174: 3137-3142.
220. ZARKESH-ESFAHANI, H. et al. 2001. High-dose leptin activates human leukocytes via receptor expression on monocytes. J. Immunol. 167: 4593-4599.
221. MANCUSO, P. et al. 2004. Leptin augments alveolar macrophage leukotriene synthesis by increasing phospholipase activity and enhancing group IVC iPLA2 (cPLA2gamma) protein expression. Am. J. Physiol. Lung Cell. Mol. Physiol. 287: 497-502.
222. DIXIT, V.D. et al. 2003. Leptin induces growth hormone secretion from peripheral blood mononuclear cells via a protein kinase C- and nitric oxide-dependent mechanism. Endocrinology 144: 5595-5603.
223. RASO, G.M. et al. 2002. Leptin potentiates IFN-gamma-induced expression of nitric oxide synthase and cyclo-oxygenase-2 in murine macrophage J774A.1. Br. J. Pharmacol. 137: 799-804.
224. CALDEFIE-CHEZET, F. et al. 2001. Leptin: a potential regulator of polymorphonuclear neutrophil bactericidal action? J. Leukoc. Biol. 69: 414-418.
225. CALDEFIE-CHEZET, F., A. POULIN & M.P. VASSON. 2003. Leptin regulates functional capacities of polymorphonuclear neutrophils. Free Radic. Res. 37: 809-814.
226. TIAN, Z. et al. 2002. Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation. Biochem. Biophys. Res. Commun. 298: 297-302.
227. HOWARD, J.K. et al. 1999. Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J. Clin. Invest. 104: 1051-1059.
228. FAROOQI, I.S. et al. 2002. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine(metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest. 110: 1093-1103.
229. LORD, G.M. et al. 1998. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394: 897-901.
230. BASTARD, J.P. et al. 2006. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur. Cytokine Netw. 17: 4-12.
231. MATARESE, G. et al. 2002. Leptin accelerates autoimmune diabetes in female NOD mice. Diabetes 51: 1356-1361.
232. SANNA, V. et al. 2003. Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses. J. Clin. Invest. 111: 241-250.
233. KOH, K.K. 2002. Effects of estrogen on the vascular wall: vasomotor function and inflammation. Cardiovasc. Res. 55: 714-726.
234. CHEN, A. et al. 2005. Diet induction of monocyte chemoattractant protein-1 and its impact on obesity. Obes. Res. 13: 1311-1320.
235. KOH, K.K., S.H. HAN & M.J. QUON. 2005. Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions. J. Am. Coll. Cardiol. 46: 1978-1985.
236. FUNAKOSHI, Y. et al. 2001. Rho-kinase mediates angiotensin II-induced monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cells. Hypertension 38: 100-104.
237. SCHERER, P.E. et al. 1995. A novel serum protein similar to C1q, produced exclusively in adipocytes. J. Biol. Chem. 270: 26746-26749.
238. KUBOTA, N. et al. 2002. Disruption of adiponectin causes insulin resistance and neointimal formation. J. Biol. Chem. 277: 25863-25866.
239. UKKOLA, O. & M. SANTANIEMI. 2002. Adiponectin: a link between excess adiposity and associated comorbidities? J. Mol. Med. 80: 696-702.
240. HOTTA, K. et al. 2000. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler. Thromb. Vasc. Biol. 20: 1595-1599.
241. BERG, A.H. et al. 2001. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat. Med. 7: 947-953.
242. CHEN, H. et al. 2003. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J. Biol. Chem. 278: 45021-45026.
243. OUCHI, N. et al. 1999. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 100: 2473-2476.
244. OUCHI, N. et al. 2000. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 102: 1296-1301.
245. FASSHAUER, M. et al. 2003. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 301: 1045-1050.
246. STEPPAN, C.M. et al. 2001. The hormone resistin links obesity to diabetes. Nature 409: 307-312.
247. STEPPAN, C.M. et al. 2005. Activation of SOCS-3 by resistin. Mol. Cell. Biol. 25: 1569-1575.
248. SCHONBECK, U. & P. LIBBY. 2001. CD40 signaling and plaque instability. Circ. Res. 89: 1092-1103.
249. ESPOSITO, K. et al. 2003. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289: 1799-1804.
250. ESPOSITO, K. et al. 2004. Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 292: 1440-1446.
251. MONZILLO, L.U. et al. 2003. Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance. Obes. Res. 11: 1048-1054.
252. GHANIM, H. et al. 2001. Suppression of nuclear factor-kappaB and stimulation of inhibitor kappaB by troglitazone: evidence for an anti-inflammatory effect and a potential antiatherosclerotic effect in the obese. J. Clin. Endocrinol. Metab. 86: 1306-1312.
253. ALJADA, A. et al. 2001. Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action? J. Clin. Endocrinol. Metab. 86: 3250-3256.
254. MOHANTY, P. et al. 2004. Evidence for a potent antiinflammatory effect of rosiglitazone. J. Clin. Endocrinol. Metab. 89: 2728-2735.
255. KATSUKI, A. 2000. Troglitazone reduces plasma levels of tumour necrosis factoralpha in obese patients with type 2 diabetes. Diabetes Obes. Metab. 2: 189-191.
256. HAFFNER, S.M. et al. 2002. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 106: 679-684.
257. YU, J.G. et al. 2002. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 51: 2968-2974.
258. HIROSE, H. et al. 2002. Effects of pioglitazone on metabolic parameters, body fat distribution, and serum adiponectin levels in Japanese male patients with type 2 diabetes. Metabolism 51: 314-317.
259. MAEDA, N. et al. 2001. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50: 2094-2099.
260. DANDONA, P. et al. Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin. J. Clin. Endocrinol. Metab. 89: 5043-5047.
261. KOH, K.K. et al. 2002. Comparative effects of diet and simvastatin on markers of thrombogenicity in patients with coronary artery disease. Am. J. Cardiol. 91: 1231-1234.
262. KOH, K.K. et al. 2002. Statin attenuates increase in C-reactive protein during estrogen replacement therapy in postmenopausal women. Circulation 105: 1531-1533.
263. TROSEID, M. et al. 2004. Exercise reduces plasma levels of the chemokines MCP-1 and IL-8 in subjects with the metabolic syndrome. Eur. Heart J. 25: 349-355.
264. PASCERI, V. et al. 2001. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 103: 2531-2534.
265. STAELS, B. et al. 1998. Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature 393: 790-793.
266. KOH, K.K. et al. 2005. Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia. Diabetes Care 28: 1419-1424.
267. KOH, K.K. et al. 2003. Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients. J. Am. Coll. Cardiol. 42: 905-910.
268. FURUHASHI, M. et al. 2003. Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension. Hypertension 42: 76-81.
269. WANG, C.H. et al. 2003. C-reactive protein upregulates angiotensin type 1 receptors in vascular smooth muscle. Circulation 107: 1783-1790.
270. KOH, K.K. et al. 2005. Vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes. Hypertension 45: 1088-1093.
271. KOH, K.K. et al. 2004. Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients. Circulation 110: 3687-3692.
272. KOH, K.K. et al. 2004. Simvastatin combined with ramipril treatment in hypercholesterolemic patients. Hypertension 44: 180-185.
273. DANDONA, P. et al. 2001. Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect? J. Clin. Endocrinol. Metab. 86: 3257-3265.
274. ALJADA, A. et al. 2002. Insulin inhibits the pro-inflammatory transcription factor early growth response gene-1 (Egr)-1 expression in mononuclear cells (MNC) and reduces plasma tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) concentrations. J. Clin. Endocrinol. Metab. 87: 1419-1422.
275. DANDONA, P. & A. ALJADA. 2002. A rational approach to pathogenesis and treatment of type 2 diabetes mellitus, insulin resistance, inflammation, and atherosclerosis. Am. J. Cardiol. 90: 27G-33G.
276. TAKEBAYASHI, K., Y. ASO & T. INUKAI. 2004. Initiation of insulin therapy reduces serum concentrations of high-sensitivity C-reactive protein in patients with type 2 diabetes. Metabolism 53: 693-699.
277. STENTZ, F.B. et al. 2004. Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises. Diabetes 53: 2079-2086.
278. CHAUDHURI, A. et al. 2004. Anti-inflammatory and profibrinolytic effect of insulin in acute ST-segment-elevation myocardial infarction. Circulation 109: 849-854.
279. JONASSEN, A.K. et al. 2001. Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling. Circ. Res. 89: 1191-1198.
280. Di ROCCO, P. et al. 2004. Lowered tumor necrosis factor receptors, but not increased insulin sensitivity, with infliximab. Obes. Res. 12: 734-739.
281. PAQUOT, N. et al. 2000. No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients. J. Clin. Endocrinol. Metab. 85: 1316-1319.
282. OFEI, F. et al. 1996. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 45: 881-885.
283. KANETO, H. et al. 2004. Possible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide. Nat. Med. 10: 1128-1132.
284. KANETO, H. et al. 2004. Oxidative stress and the JNK pathway as a potential therapeutic target for diabetes. Drug News Perspect. 17: 447-453.
285. PEELMAN, F. et al. 2004. Mapping of the leptin binding sites and design of a leptin antagonist. J. Biol. Chem. 279: 41038-41046.