The role of insulin and the adipocytokines in regulation of vascular endothelial function

Clinical Science

Volumn 107, Issue 6, 2004, Pages 519-532

  Ritchie, Stuart A ^a,b   Ewart, Marie Ann ^a,b   Perry, Colin G ^b   Connell, John M C ^b   Salt, Ian P ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

^b WESTERN INFIRMARY   (United Kingdom)

Author keywords

Adipocytokine; Diabetes; Endothelium; Insulin; Obesity; Vascular function

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ACYLATION STIMULATING PROTEIN; ADIPOCYTOKINE; ADIPONECTIN; ADIPOPHILIN; ADIPSIN; AGOUTI PROTEIN; ANGIOTENSINOGEN; ANTIDIABETIC AGENT; CELL PROTEIN; CYTOKINE; INSULIN; INTERLEUKIN 4; INTERLEUKIN 8; LEPTIN; METFORMIN; NITRIC OXIDE; PLASMINOGEN ACTIVATOR INHIBITOR; RESISTIN; SIBUTRAMINE; SULFONYLUREA; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ADIPOCYTE; EXERCISE; GLUCOSE HOMEOSTASIS; HUMAN; INSULIN METABOLISM; INSULIN RESISTANCE; INSULIN SENSITIVITY; OBESITY; PARACRINE SIGNALING; PRIORITY JOURNAL; PROTEIN SECRETION; REVIEW; VASCULAR ENDOTHELIUM; WEIGHT REDUCTION;

ADIPOSE TISSUE; ANTI-OBESITY AGENTS; CYTOKINES; ENDOTHELIUM, VASCULAR; HUMANS; INSULIN; INSULIN RESISTANCE; METABOLIC SYNDROME X; OBESITY; SIGNAL TRANSDUCTION;

EID: 10344262018     PISSN: 01435221     EISSN: None     Source Type: Journal    
DOI: 10.1042/CS20040190     Document Type: Review

References (211)

1. Nesto, R. W. (2004) Correlation between cardiovascular disease and diabetes mellitus: current concepts. Am. J. Med. 116, 11S-22S
2. Laight, D. W., Carrier, M. J. and Anggard, E. E. (2000) Antioxidants, diabetes and endothelial dysfunction. Cardiovasc. Res. 47, 457-464
3. Reddy, K. G., Nair, R. N., Sheehan, H. M. and Hodgson, J. M. (1994) Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. J. Am. Coll. Cardiol. 23, 833-843
4. Suwaidi, J. A., Hamasaki, S., Higano, S. T., Nishimura, R. A., Holmes, Jr, D. R. and Lerman, A. (2000) Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 101, 948-954
5. Lin, K. Y., Ito, A., Asagami, T. et al. (2002) Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminhydrolase. Circulation 106, 987-992
6. Shinozaki, K., Kashiwagi, A., Masada, M. and Okamura, T. (2003) Stress and vascular responses: oxidative stress and endothelial dysfunction in the insulin-resistant state. J. Pharmacol. Sci. 91, 187-191
7. Taniyama, Y. and Griendling, K. K. (2003) Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension 42, 1075-1081
8. Shah, A. M. and Channon, K. M. (2004) Free radicals and redox signalling in cardiovascular disease. Heart 90, 486-487
9. Weyer, C., Bogardus, C., Mott, D. M. and Pratley, R. E. (1999) The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J. Clin. Invest. 104, 787-794
10. Williams, S. B., Cusco, J. A., Roddy, M. A., Johnstone, M. T. and Creager, M. A. (1996) Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus. J. Am. Coll. Cardiol. 27, 567-574
11. Vogel, R. A. (1999) Cholesterol lowering and endothelial function. Am. J. Med. 107, 479-487
12. Cleland, S. J., Petrie, J. R., Small, M., Elliot, H. L. and Connell, J. M. C. (2000) Insulin action is associated with endothelial function in hypertension and type 2 diabetes. Hypertension 35, 507-511
13. Stühlger, M. C., Abbasi, F., Chu, J. W. et al. (2002) Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA, J. Am. Med. Assoc. 287, 1420-1426
14. Klaus, S. (2004) Adipose tissue as a regulator of energy balance. Curr. Drug Targets 5, 241-250
15. Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R. and Burn, P. (1995) Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science (Washington, D.C.) 269, 546-549
16. Scherer, P. E., Williams, S., Fogliano, M., Baldini, G. and Lodish, H. F. (1995) A novel serum protein similar to Cq1, produced exclusively in adipocytes. J. Biol. Chem. 270, 26746-26749
17. Hu, E., Liang, P. and Spiegelman, B. M. (1996) AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem. 271, 10697-10703
18. Maeda, K., Okubo, K., Shimomura, I., Funahashi, T., Matsuzawa, Y. and Matsubara, K. (1996) cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (adipose most abundant gene transcript 1). Biochem. Biophys. Res. Commun. 221, 286-296
19. Mohamed-Ali, V., Goodrick, S., Rawesh, A. et al. (1997) Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-α, in vivo. J. Clin. Endocrinol. Metab. 82, 4196-4200
20. Kern, P. A., Saghizadeh, M., Ong, J. M., Bosch, R. J., Deem, R. and Simsolo, R. B. (1995) The expression of tumour necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J. Clin. Invest. 95, 2111-2119
21. Steppan, C. M., Bailey, S. T., Bhat, S. et al. (2001). The hormone resistin links obesity to diabetes. Nature (London) 409, 307-312
22. Wiman, B., Chmielewska, J. and Ranby, M. (1984) Inactivation of tissue plasminogen activator in plasma. Demonstration of a complex with a new rapid inhibitor. J. Biol. Chem. 259, 3644-3647
23. Cook, K. S., Groves, D. L., Min, H. Y. and Spiegelman, B. M. (1985) A developmentally regulated mRNA from 3T3 adipocytes encodes a novel serine protease homologue. Proc. Natl. Acad. Sci. U.S.A. 82, 6480-6484
24. Maslowska, M., Scantlebury, T., Germinario, R. and Cianflone, K. (1997) Acute in vitro production of acylation stimulating protein in differentiated human adipocytes. J. Lipid Res. 38, 1-11
25. Bruun, J. M., Pedersen, S. B. and Richelsen, B. (2001) Regulation of interleukin 8 production and gene expression in human adipose tissue in vitro. J. Clin. Endocrinol. Metab. 86, 1267-1273
26. Manne, J., Argeson, A. C. and Siracusa, L. D. (1995) Mechanisms for the pleiotropic effects of the agouti gene. Proc. Natl. Acad. Sci. U.S.A. 92, 4721-4724
27. Samad, F. and Loskuttof, D. J. (1996) Elevated expression of transforming growth factor-β in adipose tissue from obese mice. Mol. Med. 2, 568-582
28. Jones, B. H., Standridge, M. K., Taylor, J. W. and Moustaid, N. (1997) Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control. Am. J. Physiol. 273, R236-R242
29. Heid, H. W., Moll, R., Schwedick, I., Rackwitz, H.-R. and Keenan, T. W. (1998) Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases. Cell Tissue Res. 294, 309-321
30. Dandona, P., Aljada, A. and Bandyopadhyay, A. (2004) Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 25, 4-7
31. Yudkin, J. S. (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
32. Jialal, I., Devaraj, S. and Venugopal, S. K. (2004) C-Reactive protein: risk marker or mediator in atherothrombosis? Hypertension 44, 6-11
33. Festa, A., Hanley, A. J. G., Tracy, R. P., D'Agostino, Jr, R. and Haffner, S. M. (2003) Inflammation in the prediabetic state is related to increased insulin resistance rather than decreased insulin secretion. Circulation 108, 1822-1830
34. Ziccardi, P., Nappo, F., Giugliano, G. et al. (2002) Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 105, 804-809
35. Baron, A. D. and Brechtel, G. (1993) Insulin differentially regulates systemic and skeletal muscle vascular resistance. Am. J. Physiol. 265, E61-E67
36. Baron, A. D. (1994) Hemodynamic actions of insulin. Am. J. Physiol. 267, E187-E202
37. Anderson, E. A., Hoffman, R. P., Balon, T. W., Sinkey, C. A. and Mark, A. L. (1991) Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J. Clin. Invest. 87, 2246-2252
38. Laakso, M., Edelman, S. V., Brechtel, G. and Baron, A. D. (1990) Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. J. Clin. Invest. 85, 1844-1852
39. Cardillo, C., Nambi, S. S., Kilcoyne, C. M. et al. (1999) Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation 100, 820-825
40. Scherrer, U., Randin, D., Vollenweider, L. and Nicod, P. (1994) Nitric oxide release accounts for insulin's vascular effect in humans. J. Clin. Invest. 94, 2511-2515
41. Eringa, E. C., Stehouwer, C. D., Merlijn, T., Westerhof, N. and Sipkema, P. (2002) Physiological concentrations of insulin induce endothelin-mediated vasoconstriction during inhibition of NOS or PI3-kinase in skeletal muscle arterioles. Cardiovasc. Res. 56, 464-471
42. Hasdai, D., Rizza, R. A., Holmes, Jr, D. R., Richardson, D. M., Cohen, P. and Lerman, A. (1998) Insulin and insulin-like growth factor-1 cause coronary vasorelaxation in vitro. Hypertension 32, 228-234
43. McKay, M. K. and Hester, R. L. (1996) Role of nitric oxide, adenosine and ATP-sensitive potassium channels in insulin-induced vasodilation. Hypertension 28, 202-208
44. Steinberg, H. O., Brechtel, G., Johnson, A., Fineberg, N. and Baron, A. D. (1994) Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J. Clin. Invest. 94, 1172-1174
45. Zeng, G. and Quon, M. J. (1996) Insulin-stimulated production of nitric oxide is inhibited by wortmannin-direct measurement in vascular endothelial cells. J. Clin. Invest. 98, 894-898
46. Vallance, P., Collier, J. and Moncada, S. (1989) Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet ii, 997-1000
47. Dela, F., Larsen, J. J., Mikines, K. J. and Galbo, H. (1995) Normal effect of insulin to stimulate leg blood flow in NIDDM. Diabetes 44, 221-226
48. Tack, C. J., Lutterman, J. A., Vervoort, G., Thien, T. and Smits, P. (1996) Activation of the sodium-potassium pump contributes to insulin-induced vasodilation in humans. Hypertension 28, 426-432
49. Ueda, S., Petrie, J. R., Cleland, S. J., Elliot, H. L. and Connell, J. M. C. (1998) The vasodilating effect of insulin is dependent on local glucose uptake: a double blind, placebo-controlled study. J. Clin. Endocrinol. Metab. 83, 2126-2133
50. Laight, D. W., Kaw, A. V., Carrier, M. J. and Anggard, E. E. (1998) Pharmacological modulation of endothelial function by insulin in the rat aorta. J. Pharm. Pharmacol. 50, 1117-1120
51. Wambach, G. K. and Liu, D. (1992) Insulin attenuates vasoconstriction by noradrenaline, seratonin and potassium chloride in rat mesenteric arterioles. Clin. Exp. Hypertens. A. 14, 733-740
52. Abe, H., Yamada, N., Kamata, K. et al. (1998) Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1. J. Clin. Invest. 101, 1784-1788
53. Federici, M., Pandolfi, A., De Filippis, E. A. et al. (2004) G972R IRS-1 variant impairs insulin regulation of endothelial nitric oxide synthase in cultured human endothelial cells. Circulation 109, 399-405
54. Whiteman, E. L., Cho, H. and Birnbaum, M. J. (2002) Role of Akt/protein kinase B in metabolism. Trends. Endocrinol. Metab. 13, 444-451
55. Kim, F., Gallis, B. and Corson, M. A. (2001) TNF-α inhibits flow and insulin signaling leading to NO production in aortic endothelial cells. Am. J. Physiol. Cell Physiol. 280, C1057-C1065
56. Montagnani, M., Ravichandran, L. V., Chen, H., Esposito, D. L. and Quon, M. J. (2002) Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells. Mol. Endocrinol. 16, 1931-1942
57. Salt, I. P., Morrow, V. A., Brandie, F. M., Connell, J. M. C. and Petrie, J. R. (2003) High glucose inhibits insulin-stimulated nitric oxide production without reducing eNOS Ser1177 phosphorylation in human aortic endothelial cells. J. Biol. Chem. 278, 18791-18797
58. Dimmeler, S., Fleming, I., Fisslthaler, B., Hermann, C., Busse, R. and Zeiher, A. M. (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature (London) 399, 601-605
59. Fulton, D., Gratton, J.-P., McCabe, T. J. et al. (1999) Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature (London) 399, 597-601
60. Michell, B. J., Griffiths, J. E., Mitchelhill, K. I. et al. (1999) The Akt kinase signals directly to endothelial nitric oxide synthase. Curr. Biol. 9, 845-848
61. Wallerath, T., Kunt, T., Forst, T. et al. (2003) Stimulation of endothelial nitric oxide synthase by proinsulin C-peptide. Nitric Oxide 9, 95-102
62. Randriamboavonjy, V., Schrader, J., Busse, R. and Fleming, I. (2004) Insulin induces the release of vasodilator compounds from platelets by a nitric oxide-G kinase-VAMP-3-dependent pathway. J. Exp. Med. 199, 347-356
63. Cardillo, C., Kilcoyne, C. M., Nambi, S. S., Cannon, III, R. O., Quon, M. J. and Panza, J. A. (1998) Vasodilator response to systemic but not to local hyperinsulinemia in the human forearm. Hypertension 32, 740-745
64. Yki-Jarvinen, H. and Utriainen, T. (1998) Insulin-induced vasodilatation: physiology or pharmacology? Diabetologia 41, 369-379
65. Yki-Jarvinen, H. (2003) Insulin resistance and endothelial dysfunction. Best Pract. Res. Clin. Endocrinol. Metab. 17, 411-430
66. Webb, D. J. (1997) Endothelin: from molecule to man. Br. J. Clin. Pharmacol. 44, 9-20
67. Piatti, P. M., Monti, L. D., Galli, L. et al. (2000) Relationship between endothelin-1 concentration and metabolic alterations typical of the insulin resistance syndrome. Metab., Clin. Exp. 49, 748-752
68. Schroeder, Jr, C. A., Chen, Y.-L. and Messina, E. J. (1999) Inhibition of NO synthesis or endothelium removal reveals a vasoconstrictor effect of insulin on isolated arterioles. Am. J. Physiol. 276, H815-H820
69. Ferri, C., Carlomagno, A., Coassin, S. et al. (1995) Circulating endothelin-1 levels increase during euglycemic hyperinsulinemic clamp in lean NIDDM men. Diabetes Care 18, 226-233
70. Eringa, E. C., Stehouwer, C. D. A., van Nieuw Amerongen, G. P., Ouwehand, N. and Sipkema, P. (2004) Vasoconstrictor effect of insulin in skeletal muscle arterioles are mediated by ERK1/2 activation in endothelium. Am. J. Physiol. Heart Circ. Physiol., DOI 10.1152/ajpheart.00067.2004
71. Vicent, D., Ilany, J., Kondo, T. et al. (2003) The role of endothelial insulin signalling in the regulation of vascular tone and insulin resistance. J. Clin. Invest. 111, 1373-1380
72. Aljada, A., Saadeh, R., Assian, E., Ghanim, H. and Dandona, P. (2000) Insulin inhibits the expression of intercellular adhesion molecule-1 by human aortic endothelial cells through stimulation of nitric oxide. J. Clin. Endocrinol. Metab. 85, 2572-2575
73. Ding, Y., Vaziri, N. D., Coulson, R., Kamana, V. S. and Roh, D. D. (2000) Effects of simulated hyperglycemia, insulin, and glucagon on endothelial nitric oxide synthase expression. Am. J. Physiol. Endocrinol. Metab. 279, E11-E17
74. Aljada, A., Ghanim, H., Saadeh, R. and Dandona, P. (2001) Insulin inhibits NFκB and MCP-1 expression in human aortic endothelial cells. J. Clin. Endocrinol. Metab. 86, 450-453
75. Kuboki, K., Jiang, Z. Y., Takahara, N. et al. (2000) Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: a specific vascular action of insulin. Circulation 101, 676-681
76. Puente Navazo, M. D., Chettab, K., Duhault, J., Koenig-Berard, E. and McGregor, J. L. (2001) Glucose and insulin modulate the capacity of endothelial cells (HUVEC) to express P-selectin and bind a monocytic cell line (U937). Thromb. Haemostasis 86, 680-685
77. Zeng, G. Y., Nystrom, F. H., Ravichandran, L. V. et al. (2000) Roles for insulin receptor, PI3-kinase and Akt in insulin signalling pathways related to production of nitric oxide in human vascular endothelial cells. Circulation 101, 1539-1545
78. Aljada, A., Ghanim, H., Assian, E. and Dandona, P. (2002) Tumour necrosis factor-α inhibits insulin-induced increase in endothelial nitric oxide synthase and reduces insulin receptor content and phosphorylation in human aortic endothelial cells. Metab., Clin. Exp. 51, 487-491
79. Sasaoka, T., Ishiki, M., Sawa, T. et al. (1996) Comparison of the insulin and insulin-like growth factor 1 mitogenic intracellular signaling pathways. Endocrinology 137, 4427-4434
80. Montagnani, M., Golovchenko, I., Kim, I. et al. (2002) Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells. J. Biol. Chem. 277, 1794-1799
81. Jiang, Z. Y., Lin, Y. W., Clemont, A. et al. (1999) Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. J. Clin. Invest. 104, 447-457
82. Festa, A., D'Agostino, Jr, R., Williams, K. et al. (2001) The relation of body fat mass and distribution to markers of chronic inflammation. Int. J. Obes. Relat. Metab. Disord. 25, 1407-1415
83. Takami, R., Takeda, N., Hayashi, M. et al. (2001) Body fatness and fat distribution as predictors of metabolic abnormalities and early carotid atherosclerosis. Diabetes Care 24, 1248-1252
84. Considine, R. V., Sinha, M. K., Heiman, M. L. et al. (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 334, 292-295
85. Mizuno, T. M., Kleopoulos, S. P., Bergen, H. T., Roberts, J. L., Priest, C. A. and Mobbs, C. V. (1998) Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting in ob/ob and db/db mice, but is stimulated by leptin. Diabetes 47, 294-297
86. Schwartz, M. W., Seeley, R. J., Campfield, L. A., Burn, P. and Baskin, D. G. (1996) Identification of targets of leptin action in rat hypothalamus. J. Clin. Invest. 98, 1101-1106
87. Schwartz, M. W., Erickson, J. C., Baskin, D. G. and Palmiter, R. D. (1998) Effect of fasting and leptin deficiency on hypothalamic neuropeptide Y gene transcription in vivo revealed by expression of a LacZ reporter gene. Endocrinology 139, 2629-2635
88. Zabeau, L., Lavens, D., Peelman, F., Eyckerman, S., Vandekerckhove, J. and Tavernier, J. (2003) The ins and outs of leptin receptor activation. FEBS Lett. 546, 45-50
89. Farooqi, I. S., Matarese, G., Lord, G. M. 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
90. Bouloumie, A., Marumo, T., Lafontan, M. and Busse, R. (1999) Leptin induces oxidative stress in human endothelial cells. FASEB J. 13, 1231-1238
91. Park, H. Y., Kwon, H. M., Lim, H. J. et al. (2001) 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
92. Yamagishi, S. I., Edelstein, D., Du, X. L., Kaneda, Y., Guzman, M. and Brownlee, M. (2001) Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J. Biol. Chem. 276, 25096-25100
93. Banks, W. A. and Farrell, C. L. (2003) Impaired transport of leptin across the blood-brain barrier in obesity is acquired and reversible. Am. J. Physiol. Endocrinol. Metab. 285, E10-E15
94. Bjorbaek, C., El-Haschimi, K., Frantz, J. D. and Flier, J. S. (1999) The role of SOCS-3 in leptin signaling and leptin resistance. J. Biol. Chem. 274, 30059-30065
95. Bouloumie, A., Drexler, H. C. A., Lafontan, M. and Busse, R. (1998) Leptin, the product of Ob gene, promotes angiogenesis. Circ. Res. 83, 1059-1066
96. Sierra-Honigmann, M. R., Nath, A. K., Murakami, C. et al. (1998) Biological action of leptin as an angiogenic factor. Science (Washington, D.C.) 281, 1683-1686
97. Schafer, K., Halle, M., Goeschen, C. et al. (2004) Leptin promotes vascular remodelling and neointimal growth in mice. Arterioscler., Thromb., Vasc. Biol. 24, 112-117
98. Singhal, A., Farooqi, S., Cole, T. J. et al. (2002) Influence of leptin on arterial distensibility. Circulation 106, 1919-1924
99. Gainsford, T., Willson, T. A., Metcalf, D. et al. (1996) Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc. Natl. Acad. Sci. U.S.A. 93, 14564-14568
100. Werner, N. and Nickenig, G. (2004) From fat fighter to risk factor, the zigzag trek of leptin. Arterioscler., Thromb., Vasc. Biol. 24, 7-9
101. Porreca, E., Di Febbo, C., Fusco, L., Moretta, V., Di Nisio, M. and Cuccurullo, F. (2004) Soluble thrombomodulin and vascular adhesion molecule-1 are associated to leptin plasma levels in obese women. Atherosclerosis 172, 175-180
102. Hukshorn, C. J., Lindeman, J. H., Toet, K. H. et al. (2004) Leptin and the proinflammatory state associated with human obesity. J. Clin. Endocrinol. Metab. 89, 1773-1778
103. Goetze, S., Bungenstock, A., Czupalla, C. et al. (2002) Leptin induces endothelial cell migration through Akt, which is inhibited by PPAR-γ ligands. Hypertension 40, 748-754
104. Lembo, G., Vecchione, C., Fratta, L. et al. (2000) Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes 49, 293-297
105. Matsuda, K., Teragawa, H., Fukuda, Y., Nakagawa, K., Higashi, Y. and Chayama, K. (2003) Leptin causes nitric-oxide independent coronary artery vasodilation in humans. Hypertens. Res. 26, 147-152
106. Kimura, K., Tsuda, K., Baba, A. et al. (2000) Involvement of nitric oxide in endothelium-dependent arterial relaxation by leptin. Biochem. Biophys. Res. Commun. 273, 745-749
107. Nakagawa, K., Higashi, Y., Sasaki, S., Oshima, T., Matsuura, H. and Chayama, K. (2002) Leptin causes vasodilation in humans. Hypertens. Res. 25, 161-165
108. Vecchione, C., Maffei, A., Colella, S. et al. (2002) Leptin effect on endothelial nitric oxide is mediated through Akt-endothelial nitric oxide synthase phosphorylation pathway. Diabetes 51, 168-173
109. Pajvani, U. B., Du, X., Combs, T. P. et al. (2003) Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications for metabolic regulation and bioactivity. J. Biol. Chem. 278, 9073-9085
110. Arita, Y., Kihara, S., Ouchi, N. et al. (1999) Paradoxical decrease of an adipose specific protein, adiponectin, in obesity. Biochem. Biophys. Res. Commun. 257, 79-83
111. Weyer, C., Funahashi, T., Tanaka, S. et al. (2001) Hypoadiponectinaemia in obesity and Type 2 diabetes: close association with insulin resistance and hyperinsulinaemia. J. Clin. Endocrinol. Metab. 86, 1930-1935
112. Hotta, K., Funahashi, T., Arita, Y. et al. (2000) Plasma concentrations of a novel, adipose specific protein adiponectin, in type II diabetic patients. Arterioscler., Thromb., Vasc. Biol. 20, 1595-1599
113. Comuzzie, A. G., Funahashi, T., Sonnenberg, G. et al. (2001) The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J. Clin. Endocrinol. Metab. 86, 4321-4325
114. Lindsay, R. S., Funahashi, T., Krakoff, J. et al. (2003) Genome-wide linkage analysis of serum adiponectin in the Pima indian population. Diabetes 52, 2419-2425
115. Kubota, N., Terauchi, Y., Yamauchi, T. et al. (2002) Disruption of adiponectin causes insulin resistance and neointimal formation. J. Biol. Chem. 277, 25863-25866
116. Maeda, N., Shimomura, I., Kishida, K. et al. (2002) Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat. Med. 8, 731-737
117. Lindsay, R. S., Funahashi, T., Hanson, R. L. et al. (2002) Adiponectin and development of type 2 diabetes in the Pima Indian Population. Lancet 360, 57-58
118. Yamauchi, T., Kamon, J., Waki, H. et al. (2001) The fat derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 7, 941-946
119. Yamauchi, T., Kamon, J., Minokoshi, Y. et al. (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med. 8, 1288-1295
120. Yamauchi, T., Kamon, J., Ito, Y. et al. (2003) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature (London) 423, 762-769
121. Tan, K. C., Xu, A., Chow, W. C. et al. (2004) Hypoadiponectinaemia is associated with impaired endothelium-dependant vasodilatation. J. Clin. Endocrinol. Metab. 89, 765-769
122. Shimabukuro, M., Higa, N., Asahi, T. et al. (2003) Hypoadiponectinaemia is closely linked to endothelial dysfunction in man. J. Clin. Endocrinol. Metab. 88, 3236-3240
123. Kawanami, D., Maemura, K., Takeda, N. et al. (2004) Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem. Biophys. Res. Commun. 314, 415-419
124. Morrow, V. A., Foufelle, F., Connell, J. M. C., Petrie, J. R., Gould, G. W. and Salt, I. P. (2003) Direct activation of AMP-activated protein kinase stimulates nitric oxide synthesis in human aortic endothelial cells. J. Biol. Chem. 278, 31629-31639
125. Chen, H., Montagnani, M., Funahashi, T., Shimomura, I. and Quon, M. J. (2003) Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J. Biol. Chem. 278, 45021-45026
126. Hattori, Y., Suzuki, M., Hattori, S. and Kasai, K. (2003) Globular adiponectin upregulates nitric oxide production in vascular endothelial cells. Diabetologia 46, 1543-1549
127. Ouchi, N., Kobayashi, H., Kihara, S. et al. (2004) Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J. Biol. Chem. 279, 1304-1309
128. Ouchi, N., Kihara, S., Arita, Y. et al. (1999) Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein. Circulation 100, 2473-2476
129. Ouchi, N., Kihara, S., Arita, Y. et al. (2001) Adipocyte-derived plasma protein adiponectin, suppress lipid accumulation and class A scavenger receptor expression in human monocyte derived macrophages. Circulation 103, 1057-1063
130. Podor, T. J., Jirik, F. R., Loskutoff, D. J., Carson, D. A. and Lotz, M. (1998) Human endothelial cells produce IL-6. Lack of responses to exogenous IL-6. Ann. N.Y. Acad. Sci. 557, 374-385
131. Taga, T., Hibi, M., Hirata, Y. et al. (1989) Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell (Cambridge, Mass.) 58, 573-581
132. Kim, H. J., Higashimori, T., Park, S. Y. et al. (2004) Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vitro. Diabetes 53, 1060-1067
133. Orshal, J. M. and Khalil, R. A. (2004) Interleukin-6 impairs endothelium-dependent NO-cGMP-mediated relaxation and enhances contraction in systemic vessels of pregnant rats. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 286, R1013-R1023
134. Hernandez-Rodriguez, J., Seggara, M., Vilardell, C. et al. (2003) Elevated production of interleukin-6 is associated with a lower incidence of disease-related ischemic events in patients with giant-cell arteritis: angiogenic activity of interleukin-6 as a potential protective mechanism. Circulation 107, 2428-2434
135. Holzinger, C., Weissinger, E., Zuckermann, A. et al. (1993) Effects of interleukin-1, -2, -4, -6, interferon-γ and granulocyte/macrophage colony stimulating factor on human vascular endothelial cells. Immunol. Lett. 35, 109-117
136. Bhakdi, S., Torzewski, M., Klouche, M. and Hemmes, M. (1999) Complement and atherogenesis: binding of CRP to degraded, nonoxidised LDL enhances complement activation. Arterioscler., Thromb., Vasc. Biol. 19, 109-117
137. Pasceri, V., Willerson, J. T. and Yeh, E. T. (2000) Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 102, 2165-2168
138. Pasceri, V., Cheng, J. S., Willerson, J. T., Yeh, E. T. and Chang, J. (2001) Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 103, 2531-2534
139. Venugopal, S. K., Deveraj, S., Yuhanna, I., Shaul, P. and Jialal, I. (2002) Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation 106, 1439-1441
140. Verma, S., Wang, C. H., Li, S. H. et al. (2002) A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 106, 913-919
141. Wajant, H., Pfizenmaier, K. and Scheurich, P. (2003) Tumor necrosis factor signaling. Cell Death Differ. 10, 45-65
142. Warne, J. P. (2003) Tumour necrosis factor α: a key regulator of adipose tissue mass. J. Endocrinol. 177, 351-355
143. Locksley, R. M., Killeen, N. and Lenardo, M. J. (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104, 487-501
144. Hotamisligil, G. S., Shargill, N. S. and Speigelman, B. M. (1993) Adipose expression of tumour necrosis factor α: direct role in obesity-linked insulin resistance. Science (Washington, D.C.) 259, 87-91
145. Hotamisligil, G. S., Arner, P., Caro, J. F., Atkinson, R. L. and Speigelman, B. M. (1995) Increased adipose tissue expression of tumour necrosis factor-α in human obesity and insulin resistance. J. Clin. Invest. 95, 2409-2415
146. Uysal, K. T., Wiesbrock, S. M., Marino, M. M. and Hotamisligil, G. S. (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-α function. Nature (London) 389, 610-614
147. Ofei, F., Hurel, S., Newkirk, J., Sopwith, M. and Taylor, R. (1996) Effects of an engineered human anti-TNF-α antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 45, 881-885
148. Paquot, N., Castillo, M. J., Lefebvre, P. J. and Scheen, A. J. (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
149. Myers, P. R., Parker, J. L., Tanner, M. A. and Adams, H. R. (1994) Effects of cytokines tumour necrosis factor α and interleukin 1β on endotoxin mediated inhibition of endothelium derived relaxing factor bioactivity and nitric oxide production in vascular endothelium. Shock 1, 73-78
150. Wang, P., Ba, Z. F. and Chaudry, I. H. (1994) Administration of TNF-α in vivo depresses endothelium dependant relaxation. Am. J. Physiol. 266, H2535-H2541
151. Bhagat, K. and Valance, P. (1997) Inflammatory cytokines impair endothelium-dependant dilatation in human veins in vivo. Circulation 96, 3042-3047
152. Yoshizumi, M., Perrella, M. A., Burnett, Jr, J. C. and Lee, M. E. (1993) Tumour necrosis factor down regulates endothelial nitric oxide synthase m-RNA by shortening its half life. Circ. Res. 73, 205-209
153. De Keulenaer, G. W., Alexander, R. W., Ushio-Fukai, M., Ishizaka, N. and Griendling, K. K. (1998) Tumour necrosis factor α activates a p22phox based NADH oxidase in vascular smooth muscle. Biochem. J. 329, 653-657
154. Hermann, C., Assmus, B., Urbich, C., Zeiher, A. M. and Dimmeler, S. (2000) Insulin-mediated stimulation of protein kinase Akt: a potent survival signalling cascade for endothelial cells. Arterioscler., Thromb., Vasc. Biol. 20, 402-409
155. Sata, M. and Walsh, K. (1998) TNFα regulation of Fas ligand expression on the vascular endothelium modulates leukocyte extravasation. Nat. Med. 4, 415-420
156. Takemura, Y., Fukuo, K., Yasuda, O. et al. (2004) Fas signaling induces Akt activation and upregulation of endothelial nitric oxide synthase expression. Hypertension 43, 880-884
157. Patel, J. N., Jager, A., Schalkwijk, C. et al. (2002) Effects of TNF-α in the human forearm: blood flow and endothelin-1 release. Clin. Sci. 103, 405-415
158. Grau, G. E. and Lou, J. (1993) TNF in vascular pathology: the importance of platelet-endothelium interactions. Res. Immunol. 144, 355-363
159. Maroni, P., Bendinelli, P. and Picoletti, R. (2003) Early intracellular events induced by in vivo leptin treatment in mouse skeletal muscle. Mol. Cell. Endocrinol. 201, 109-121
160. Pérez, C., Fernández-Galaz, C., Fernández- Agulló, T. et al. (2004) Leptin impairs insulin signalling in rat adipocytes. Diabetes 53, 347-353
161. Lagathu, C., Bastard, J. P., Auclair, M., Maachi, M., Capeau, J. and Caron, M. (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
162. Rotter, V., Nagaev, I. and Smith, U. (2003) Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-α, overexpressed in human fat cells from insulin-resistant subjects. J. Biol. Chem. 278, 45777-45784
163. Senn, J. J., Klover, P. J., Novak, I. A. et al. (2003) Supressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J. Biol. Chem. 278, 13740-13746
164. 307. J. Biol. Chem. 275, 9047-9054
165. Gao, Z., Hwang, D., Bataille, F. et al. (2002) Serine phosphorylation of insulin receptor substrate 1 by inhibitor κB kinase complex. J. Biol. Chem. 277, 48115-48121
166. Medina, E. A., Stanhope, K. L., Mizuno, T. M. et al. (1999) Effects of tumor necrosis factor α on leptin secretion and gene expression: relationship to changes of glucose metabolism in isolated rat adipocytes. Int. J. Obes. Relat. Metab. Disord. 23, 896-903
167. Zhang, H. H., Kumar, S., Barnett, A. H. and Eggo, M. C. (2000) Tumour necrosis factor-α exerts dual effects on human adipose leptin synthesis and release. Mol. Cell. Endocrinol. 159, 79-88
168. Bruun, J. M., Pedersen, S. B., Kristensen, K. and Richelsen, B. (2002) Effects of pro-inflammatory cytokines and chemokines on leptin production in
169. Finck, B. N. and Johnson, R. W. (2000) Tumor necrosis factor (TNF)-α induces leptin production through the p55 TNF receptor. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 278, R537-R543
170. Kirchgessner, T. G., Uysal, K. T., Wiesbrock, S. M., Marino, M. W. and Hotamisligil, G. S. (1997) Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes. J. Clin. Invest. 100, 2777-2782
171. Bruun, J. M., Lihn, A. S., Verdich, C. et al. (2003) Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am. J. Physiol. Endocrinol. Metab. 285, E527-E533
172. Delporte, M. L., Ait El Mkadem, S., Quisquater, M. and Brichard, S. M. (2004) Leptin treatment markedly increased plasma adiponectin, but barely decreased plasma resistin of ob/ob mice. Am. J. Physiol. Endocrinol. Metab. 287, E446-E453
173. Ouchi, N., Kihara, S., Arita, Y. et al. (2000) Adiponectin, an adipocyte derived plasma protein inhibits endothelial NF-κB signalling through a c-AMP dependant pathway. Circulation 102, 1296-1301
174. Xydakis, A. M., Case, C. C., Jones, P. H. et al. (2004) Adiponectin, inflammation, and the expression of the metabolic syndrome in obese individuals: the impact of rapid weight loss through caloric restriction. J. Clin. Endocrinol. Metab. 89, 2697-2703
175. Ryan, A. S., Nicklas, B. J., Berman, D. M. and Elahi, D. (2003) Adiponectin levels do not change with moderate dietary induced weight loss and exercise in obese postmenopausal women. Int. J. Obes. Relat. Metab. Disord. 27, 1066-1071
176. Boudou, P., Sobngwi, E., Mauvais-Jarvis, F., Vexiau, P. and Gautier, J. F. (2003) Absence of exercise-induced variations in adiponectin levels despite decreased abdominal adiposity and improved insulin sensitivity in type 2 diabetic men. Eur. J. Endocrinol. 149, 421-424
177. Esposito, K., Pontillo, A., Di Palo, C., Giugliano, G., Masella, M., Marfella, R. and Giugliano, D. (2003) Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA, J. Am. Med. Assoc. 289, 1799-1804
178. Monzillo, L. U., Hamdy, O., Horton, E. S. et al. (2003) Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance. Obesity Res. 11, 1048-1054
179. Klein, S., Fontana, L., Young, V. L. et al. (2004) Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N. Engl. J. Med. 350, 2549-2557
180. Yang, W. S., Lee, W. J., Funahashi, T. et al. (2001) Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J. Clin. Endocrinol. Metab. 86, 3815-3819
181. Valsamakis, G., McTernan, P. G., Chetty, R. et al. (2004) Modest weight loss and reduction in waist circumference after medical treatment are associated with favourable changes in serum adipocytokines. Metab., Clin. Exp. 53, 430-434
182. Abbasi, F., Lamendola, C., McLaughlin, T., Hayden, J., Reaven, G. M. and Reaven, P. D. (2004) Plasma adiponectin concentrations do not increase in association with moderate weight loss in insulin-resistant, obese women. Metab., Clin. Exp. 53, 280-283
183. Yudkin, J. S., Panahloo, A., Stehouwer, C. et al. (2000) The influence of improved glycaemic control with insulin and sulphonylureas on acute phase and endothelial markers in Type II diabetic subjects. Diabetologia 43, 1099-1106
184. Sivitz, W. I., Wayson, S. M., Bayless, M. L. et al. (2003) Leptin and body fat in type 2 diabetes and monodrug therapy. J. Clin. Endocrinol. Metab. 88, 1543-1553
185. Carlsen, S., Waage, A., Grill, V. and Folling, I. (1998) Metformin increases circulating tumour necrosis factor alpha levels in non-obese non-diabetic patients with coronary heart disease. Cytokine 10, 66-69
186. Ciaraldi, T. P., Kong, A. P., Chu, N. V. et al. (2002) Regulation of glucose transport and insulin signalling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects. Diabetes 51, 30-36
187. Phillips, S. A., Ciaraldi, T. P., Kong, A. P. et al. (2003) Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy. Diabetes 52, 667-674
188. Freuwald-Schultes, B., Oltmanns, K. M., Toschek, B. et al. (2002) Short-term treatment with metformin decreases serum leptin concentration without affecting body weight and body fat content in normal weight healthy men. Metab., Clin. Exp. 51, 531-536
189. Ozata, M., Oktenli, C., Bingoj, N. and Ozdemir, I. C. (2001) The effects of metformin and diet on plasma testosterone and leptin levels in obese men. Obesity Res. 9, 662-667
190. UK Prospective Diabetes Study (UKPDS) Group (1998) Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352, 854-865
191. Mather, K. J., Verma, S. and Anderson, T. J. (2001) Improved endothelial function with metformin in type 2 diabetes mellitus. J. Am. Coll. Cardiol. 37, 1344-1350
192. Bajaj, M., Suraamornkul, S., Piper, P. et al. (2004) Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients. J. Clin. Endocrinol. Metab. 89, 200-206
193. Yu, J. G., Javorschi, S., Hevener, A. L. et al. (2002) The effect of thiazolidinediones on plasma adiponectin levels in normal, obese and type 2 diabetic subjects. Diabetes 51, 2968-2974
194. Yang, W. S., Jeng, C. Y., Wu, T. J. et al. (2002) Synthetic peroxisome proliferators-activated receptor-gamma agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care 25, 376-380
195. Maeda, N., Takahashi, M., Funahashi, T. et al. (2001) PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipocyte derived protein. Diabetes 50, 2094-2099
196. Katsuki, A., Sumida, Y., Murata, K. et al. (2000) Troglitazone reduces plasma levels of tumour necrosis factor α in obese patients with type 2 diabetes. Diab. Obes. Metab. 2, 189-191
197. Murase, K., Odaka, H., Suzuki, M., Tayuki, N. and Ikeda, H. (1998) Pioglitazone time dependently reduces tumour necrosis factor α levels in muscle and improves metabolic abnormalities in Wistar fatty rats. Diabetologia 41, 257-264
198. Peraldi, P., Xu, M. and Speigelman, B. (1997) Thiazolidinediones block TNF-α induced inhibition of insulin signalling. J. Clin. Invest. 100, 1863-1869
199. Kallen, C. B. and Lazar, M. A. (1996) Antidiabetic thiazolidinediones inhibit leptin (ob) gene expression in 3T3-L1 adipocytes. Proc. Natl. Acad. Sci. U.S.A. 93, 5793-5796
200. Patel, N. G., Holder, J. C., Smith, S. A., Kuma, S. and Eggo, M. C. (2003) Differential regulation of lipogenesis and leptin production by independent signalling pathways and rosiglitazone during human adipocyte differentiation. Diabetes 52, 43-50
201. Owen, K. R., Donohoe, M., Ellard, S. and Hattersley, A. T. (2003) Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene. Diabetic Med. 20, 823-827
202. Sutinen, J., Hakkinen, A. M., Seppala-Lindross, A. et al. (2003) Rosiglitazone in the treatment of HAART associated lipodystrophy, a randomised double blind placebo controlled trial. Antiviral Therapy 8, 199-207
203. Pistrosch, F., Passauer, J., Fischer, S., Fuecker, K., Hanefeld, M. and Gross, P. (2004) In type 2 diabetes, rosiglitazone therapy for insulin resistance ameliorates endothelial dysfunction independent of glucose control. Diabetes Care 27, 484-490
204. Wang, T.-D., Chen, W.-J., Lin, J.-W., Chen, M.-F. and Lee, Y.-T. (2004) Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome. Am. J. Cardiol. 93, 362-365
205. Sutton, M. St. J., Rendell, M., Dandona, P. et al. (2002) A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes. Diabetes Care 25, 2058-2064
206. Natali, A., Baldeweg, S., Toschi, E. et al. (2004) Vascular effects of improving metabolic control with metformin or rosiglitazone m type 2 diabetes. Diabetes Care 27, 1349-1357
207. Satoh, N., Ogawa, Y., Usui, T. et al. (2003) Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care 26, 2493-2499
208. Mohanty, P., Aljada, A., Ghanim, H. et al. (2004) Evidence for a potent antiinflammatory effect of rosiglitazone. J. Clin. Endocrinol. Metab. 89, 2728-2735
209. Haffner, S. M., Greenberg, A. S., Weston, W. M., Chen, H., Williams, K. and Freed, M. I. (2002) Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 106, 679-684
210. Akbar, D. H. (2003) Effect of metformin and sulfonylurea on C-reactive protein level in well-controlled type 2 diabetics with metabolic syndrome. Endocrine 20, 215-218
211. Morin-Papunen, L., Rautio, K., Ruokonen, A., Hedberg, P., Puukka, M. and Tapanainen, J. S. (2003) Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 88, 4649-4654