Insulin resistance as a therapeutic target for improved endothelial function: Metformin

Current Drug Targets - Cardiovascular and Haematological Disorders

Volumn 4, Issue 1, 2004, Pages 53-63

  Brame, Lori ^a   Verma, Subodh ^b   Anderson, Todd ^c   Lteif, Amale ^a   Mather, Kieren ^a,d  

^a INDIANA UNIVERSITY   (United States)

^b UNIVERSITY OF TORONTO   (Canada)

^c UNIVERSITY OF CALGARY   (Canada)

^d NONE   (United States)

Author keywords

Endothelin; Endothelium; Insulin; Insulin resistance; Metabolic syndrome; Metformin

Indexed keywords

ACETYLCHOLINE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BIGUANIDE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENDOTHELIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INSULIN; METFORMIN; NITRIC ACID DERIVATIVE; NITROPRUSSIDE SODIUM; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PLACEBO; STREPTOZOCIN; SULFONYLUREA; VASODILATOR AGENT; VERAPAMIL;

ANTIOXIDANT ACTIVITY; BLOOD VESSEL FUNCTION; CARDIOVASCULAR RISK; CLINICAL FEATURE; CLINICAL TRIAL; CORONARY ARTERY DISEASE; DIABETES MELLITUS; DIABETIC ANGIOPATHY; DIET THERAPY; DISEASE ASSOCIATION; DRUG MECHANISM; DRUG TARGETING; ENDOTHELIUM LESION; HUMAN; HYPERTENSION; INSULIN RESISTANCE; METABOLIC SYNDROME X; NONHUMAN; REVIEW; RISK FACTOR; VASCULAR DISEASE; VASCULAR ENDOTHELIUM;

ANIMALS; DRUG DELIVERY SYSTEMS; ENDOTHELIUM, VASCULAR; HUMANS; INSULIN RESISTANCE; METFORMIN;

EID: 1642565076     PISSN: 15680061     EISSN: None     Source Type: Journal    
DOI: 10.2174/1568006043481275     Document Type: Review

References (128)

1. Suwaidi, J.A., Hamasaki, S., Higano, S.T., Nishimura, R.A., Holmes, D.R., Jr. Lerman, A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation, 2000, 101 (9), 948-954.
2. Schachinger, V., Britten, M.B. Zeiher, A.M. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation, 2000, 101 (16), 1899-1906.
3. Halcox, J.P., Schenke, W.H., Zalos, G., Mincemoyer, R., Prasad, A., Waclawiw, M.A., Nour, K.R. Quyyumi, A.A. Prognostic value of coronary vascular endothelial dysfunction. Circulation, 2002, 106 (6), 653-658.
4. Hedblad, B., Ogren, M., Janzon, L., Isacsson, S.O. Lindell, S.E. Low pulse-wave amplitude during reactive leg hyperaemia: An independent, early marker for ischaemic heart disease and death. Results from the 21-year follow-up of the prospective cohort study 'Men born in 1914', Malmo, Sweden. J. Intern. Med., 1994, 236 (2), 161-168.
5. Perticone, F., Ceravolo, R., Pujia, A., Ventura, G., Iacopino, S., Scozzafava, A., Ferraro, A., Chello, M., Mastroroberto, P., Verdecchia, P. Schillaci, G. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation, 2001, 104 (2), 191-196.
6. Heitzer, T., Schlinzig, T., Krohn, K., Meinertz, T. Munzel, T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation, 2001, 104 (22), 2673-2678.
7. Neunteufl, T., Heber, S., Katzenschlager, R., Wolfl, G., Kostner, K., Maurer, G. Weidinger, F. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am. J. Cardiol., 2000, 86 (2), 207-210.
8. Gokce, N., Keaney, J.F., Jr., Hunter, L.M., Watkins, M.T., Menzoian, J.O., Vita, J.A. Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study. Circulation, 2002, 105 (13), 1567-1572.
9. Chan, S.Y., Mancini, G.B., Kuramoto, L., Schulzer, M., Frohlich, J. Ignaszewski, A. The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease. J. Am. Coll. Cardiol., 2003, 42 (6), 1037-1043.
10. Balkau, B. and Eschwege, E. Insulin resistance: An independent risk factor for cardiovascular disease? Diabetes Obes. Metab., 1999, 1 Suppl. 1, S23-31.
11. Despres, J.P., Lamarche, B., Mauriege, P., Cantin, B., Dagenais, G.R., Moorjani, S. Lupien, P.J. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N. Engl. J. Med., 1996, 334 (15), 952-957.
12. Pyorala, M., Miettinen, H., Laakso, M. Pyorala, K. Plasma insulin and all-cause, cardiovascular, and noncardiovascular mortality: the 22-year follow-up results of the Helsinki Policemen Study. Diabetes Care, 2000, 23 (8), 1097-1102.
13. Ruige, J.B., Assendelft, W.J., Dekker, J.M., Kostense, P.J., Heine, R.J. Bouter, L.M. Insulin and risk of cardiovascular disease: A meta-analysis. Circulation, 1998, 97 (10), 996-1001.
14. Yip, J., Facchini, F.S. Reaven, G.M. Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J. Clin. Endocrinol. Metab., 1998, 83 (8), 2773-2776.
15. Steinberg, H.O., Chaker, H., Leaming, R., Johnson, A., Brechtel, G. Baron, A.D. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J. Clin. Invest., 1996, 97 (11), 2601-2610.
16. Tack, C.J., Ong, M.K., Lutterman, J.A. Smits, P. Insulin-induced vasodilatation and endothelial function in obesity/insulin resistance. Effects of troglitazone. Diabetologia, 1998, 41 (5), 569-576.
17. McVeigh, G.E., Brennan, G.M., Johnston, G.D., McDermott, B.J., McGrath, L.T., Henry, W.R., Andrews, J.W. Hayes, J.R. Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia, 1992, 35 (8), 771-776.
18. Bijlstra, P.J., Smits, P., Lutterman, J.A. Thien, T. Effect of long-term angiotensin-converting enzyme inhibition on endothelial function in patients with the insulin-resistance syndrome. J. Cardiovasc Pharmacol., 1995, 25 (4), 658-664.
19. Watts, G.F., O'Brien, S.F., Silvester, W. Millar, J.A. Impaired endothelium-dependent and independent dilatation of forearm resistance arteries in men with diet-treated non-insulin-dependent diabetes: Role of dyslipidaemia. Clin. Sci. (Lond), 1996, 91 (5), 567-573.
20. Williams, S.B., Cusco, J.A., Roddy, M.A., Johnstone, M.T., Creager, M.A. Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus. J. Am. Coll. Cardiol., 1996, 27 (3), 567-574.
21. Hogikyan, R.V., Galecki, A.T., Pitt, B., Halter, J.B., Greene, D.A. Supiano, M.A. Specific impairment of endothelium-dependent vasodilation in subjects with type 2 diabetes independent of obesity. J. Clin. Endocrinol. Metab., 1998, 83 (6), 1946-1952.
22. Caballero, A.E., Arora, S., Saouaf, R., Lim, S.C., Smakowski, P., Park, J.Y., King, G.L., LoGerfo, F.W., Horton, E.S., Veves, A. Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes, 1999, 48 (9), 1856-1862.
23. Panza, J.A., Quyyumi, A.A., Brush, J.E., Jr. Epstein, S.E. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N. Engl. J. Med., 1990, 323 (1), 22-27.
24. Higashi, Y., Oshima, T., Sasaki, N., Ishioka, N., Nakano, Y., Ozono, R., Yoshimura, M., Ishibashi, K., Matsuura, H., Kajiyama, G. Relationship between insulin resistance and endothelium-dependent vascular relaxation in patients with essential hypertension. Hypertension, 1997, 29 (1 Pt 2), 280-285.
25. Balletshofer, B.M., Rittig, K., Enderle, M.D., Volk, A., Maerker, E., Jacob, S., Matthaei, S., Rett, K., Haring, H.U. Endothelial dysfunction is detectable in young normotensive first-degree relatives of subjects with type 2 diabetes in association with insulin resistance. Circulation, 2000, 101 (15), 1780-1784.
26. Knock, G.A., McCarthy, A.L., Lowy, C., Poston, L. Association of gestational diabetes with abnormal maternal vascular endothelial function. Br J. Obstet. Gynaecol., 1997, 104 (2), 229-234.
27. Anastasiou, E., Lekakis, J.P., Alevizaki, M., Papamichael, C.M., Megas, J., Souvatzoglou, A., Stamatelopoulos, S.F. Impaired endothelium-dependent vasodilatation in women with previous gestational diabetes. Diabetes Care, 1998, 21 (12), 2111-2115.
28. Paradisi, G., Steinberg, H.O., Hempfling, A., Cronin, J., Hook, G., Shepard, M.K., Baron, A.D. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation, 2001, 103 (10), 1410-1415.
29. Steinberg, H.O., Tarshoby, M., Monestel, R., Hook, G., Cronin, J., Johnson, A., Bayazeed, B., Baron, A.D. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J. Clin. Invest., 1997, 100 (5), 1230-1239.
30. Steinberg, H.O., Paradisi, G., Hook, G., Crowder, K., Cronin, J., Baron, A.D. Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production. Diabetes, 2000, 49 (7), 1231-1238.
31. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet, 1998, 352 (9131), 854-865.
32. UKPDS 28: A randomized trial of efficacy of early addition of metformin in sulfonylurea-treated type 2 diabetes. U.K. Prospective Diabetes Study Group. Diabetes Care, 1998, 21 (1), 87-92.
33. Turner, R.C., Holman, R.R. Metformin and risk of cardiovascular disease. Cardiology, 1999, 91 (3), 203-204.
34. Fisman, E.Z., Tenenbaum, A., Benderly, M., Goldbourt, U., Behar, S., Motro, M. Antihyperglycemic treatment in diabetics with coronary disease: Increased metformin-associated mortality over a 5-year follow-up. Cardiology, 1999, 91 (3), 195-202.
35. Olsson, J., Lindberg, G., Gottsater, M., Lindwall, K., Sjostrand, A., Tisell, A., Melander, A. Increased mortality in Type II diabetic patients using sulphonylurea and metformin in combination: A population-based observational study. Diabetologia, 2000, 43 (5), 558-560.
36. Johnson, J.A., Majumdar, S.R., Simpson, S.H., Toth, E.L. Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes. Diabetes Care, 2002, 25 (12), 2244-2248.
37. Landin-Wilhelmsen, K. Metformin and blood pressure. J. Clin. Pharm. Ther., 1992, 17 (2), 75-79.
38. Giugliano, D., De Rosa, N., Di Mara, G., Marfella, R., Acampora, R., Buoninconti, R., D'Onofrio, F. Metformin improves glucose, lipid metabolism, and reduces blood pressure in hypertensive, obese women. Diabetes Care, 1993, 16 (10), 1387-1390.
39. Velazquez, E.M., Mendoza, S., Hamer, T., Sosa, F., Glueck, C.J. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism, 1994, 43 (5), 647-654.
40. Chu, N.V., Kong, A.P., Kim, D.D., Armstrong, D., Baxi, S., Deutsch, R., Caulfield, M., Mudaliar, S.R., Reitz, R., Henry, R.R., Reaven, P.D. Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes. Diabetes Care, 2002, 25 (3), 542-549.
41. Charles, M.A., Eschwege, E., Grandmottet, P., Isnard, F., Cohen, J.M., Bensoussan, J.L., Berche, H., Chapiro, O., Andre, P., Vague, P., Juhan-Vague, I., Bard, J.M., Safar, M. Treatment with metformin of non-diabetic men with hypertension, hypertriglyceridaemia and central fat distribution: The BIGPRO 1.2 trial. Diabetes Metab. Res. Rev., 2000, 16 (1), 2-7.
42. Uehara, M.H., Kohlmann, N.E., Zanella, M.T., Ferreira, S.R. Metabolic and haemodynamic effects of metformin in patients with type 2 diabetes mellitus and hypertension. Diabetes Obes. Metab., 2001, 3 (5), 319-325.
43. Glueck, C.J., Fontaine, R.N., Wang, P., Subbiah, M.T., Weber, K., Illig, E., Streicher, P., Sieve-Smith, L., Tracy, T.M., Lang, J.E., McCullough, P. Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism, 2001, 50 (7), 856-861.
44. Landin, K., Tengborn, L., Smith, U. Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. J. Intern. Med., 1991, 229 (2), 181-187.
45. Nagi, D.K., Yudkin, J.S. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. A study of two ethnic groups. Diabetes Care, 1993, 16 (4), 621-629.
46. Mather, K.J., Verma, S., Anderson, T.J. Improved endothelial function with metformin in type 2 diabetes mellitus. J. Am. Coll. Cardiol., 2001, 37 (5), 1344-1350.
47. Alberti, K.G., Zimmet, P.Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet. Med, 1998, 15 (7), 539-553.
48. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). Jama, 2001, 285 (19); 2486-2497.
49. Jiang, Z.Y., Lin, Y.W., Clemont, A., Feener, E.P., Hein, K.D., Igarashi, M., Yamauchi, T., White, M.F., King, G.L. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. J. Clin. Invest., 1999, 104 (4), 447-457.
50. Cleland, S.J., Petrie, J.R., Small, M., Elliott, H.L., Connell, J.M. Insulin action is associated with endothelial function in hypertension and type 2 diabetes. Hypertension, 2000, 35 (1 Pt 2), 507-511.
51. De Vriese, A.S., Verbeuren, T.J., Van de Voorde, J., Lameire, N.H., Vanhoutte, P.M. Endothelial dysfunction in diabetes. Br. J. Pharmacol., 2000, 130 (5), 963-974.
52. Calles-Escandon, J., Cipolla, M. Diabetes and endothelial dysfunction: A clinical perspective. Endocr. Rev., 2001, 22 (1), 36-52.
53. Baron, A.D., Steinberg, H.O., Chaker, H., Leaming, R., Johnson, A., Brechtel, G. Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans. J. Clin. Invest., 1995, 96 (2), 786-792.
54. Utriainen, T., Makimattila, S., Virkamaki, A., Bergholm, R., Yki-Jarvinen, H. Dissociation between insulin sensitivity of glucose uptake and endothelial function in normal subjects. Diabetologia, 1996, 39 (12), 1477-1482.
55. Scherrer, U., Randin, D., Vollenweider, P., Vollenweider, L., Nicod, P. Nitric oxide release accounts for insulin's vascular effects in humans. J. Clin. Invest., 1994, 94 (6), 2511-2515.
56. Mather, K., Anderson, T.J., Verma, S. Insulin action in the vasculature: Physiology and pathophysiology. J. Vasc. Res., 2001, 38 (5), 415-422.
57. Steinberg, H.O., Brechtel, G., Johnson, A., Fineberg, N., Baron, A.D. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J. Clin. Invest., 1994, 94 (3), 1172-1179.
58. Zeng, G., Nystrom, F.H., Ravichandran, L.V., Cong, L.N., Kirby, M., Mostowski, H., Quon, M.J. Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells. Circulation, 2000, 101 (13), 1539-1545.
59. Zeng, G., Quon, M.J. Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. J. Clin. Invest., 1996, 98 (4), 894-898.
60. Kuboki, K., Jiang, Z.Y., Takahara, N., Ha, S.W., Igarashi, M., Yamauchi, T., Feener, E.P., Herbert, T.P., Rhodes, C.J., King, G.L. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo : A specific vascular action of insulin. Circulation, 2000, 101 (6), 676-681.
61. Utriainen, T., Nuutila, P., Takala, T., Vicini, P., Ruotsalainen, U., Ronnemaa, T., Tolvanen, T., Raitakari, M., Haaparanta, M., Kirvela, O., Cobelli, C., Yki-Jarvinen, H. Intact insulin stimulation of skeletal muscle blood flow, its heterogeneity and redistribution, but not of glucose uptake in non-insulin-dependent diabetes mellitus. J. Clin. Invest., 1997, 100 (4), 777-785.
62. Bonadonna, R.C., Saccomani, M.P., Del Prato, S., Bonora, E., DeFronzo, R.A., Cobelli, C. Role of tissue-specific blood flow and tissue recruitment in insulin-mediated glucose uptake of human skeletal muscle. Circulation, 1998, 98 (3), 234-241.
63. Abe, H., Yamada, N., Kamata, K., Kuwaki, T., Shimada, M., Osuga, J., Shionoiri, F., Yahagi, N., Kadowaki, T., Tamemoto, H., Ishibashi, S., Yazaki, Y., Makuuchi, M. Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1. J. Clin. Invest., 1998, 101 (8), 1784-1788.
64. Schiffrin, E.L. The endothelium and control of blood vessel function in health and disease. Clin. Invest. Med., 1994, 17 (6), 602-620.
65. Ferri, C., Bellini, C., Desideri, G., Di Francesco, L., Baldoncini, R., Santucci, A., De Mattia, G. Plasma endothelin-1 levels in obese hypertensive and normotensive men. Diabetes, 1995, 44 (4), 431-436.
66. Mangiafico, R.A., Malatino, L.S., Santonocito, M., Spada, R.S. Plasma endothelin-1 concentrations in non-insulin-dependent diabetes mellitus and nondiabetic patients with chronic arterial obstructive disease of the lower limbs. Int. Angiol., 1998, 17 (2), 97-102.
67. Piatti, P.M., Monti, L.D., Galli, L., Fragasso, G., Valsecchi, G., Conti, M., Gernone, F., Pontiroli, A.E. Relationship between endothelin-1 concentration and metabolic alterations typical of the insulin resistance syndrome. Metabolism, 2000, 49 (6), 748-752.
68. Mather, K.J., Mirzamohammadi, B., Lteif, A., Steinberg, H.O., Baron, A.D. Endothelin contributes to basal vascular tone and endothelial dysfunction in human obesity and type 2 diabetes. Diabetes, 2002, 51 (12), 3517-3523.
69. Cardillo, C., Campia, U., Bryant, M.B., Panza, J.A. Increased activity of endogenous endothelin in patients with type II diabetes mellitus. Circulation, 2002, 106 (14), 1783-1787.
70. Cardillo, C., Campia, U., Kilcoyne, C.M., Bryant, M.B., Panza, J.A. Improved endothelium-dependent vasodilation after blockade of endothelin receptors in patients with essential hypertension. Circulation, 2002, 105 (4), 452-456.
71. Flowers, M.A., Wang, Y., Stewart, R.J., Patel, B., Marsden, P.A. Reciprocal regulation of endothelin-1 and endothelial constitutive NOS in proliferating endothelial cells. Am. J. Physiol., 1995, 269 (6 Pt 2), H1988-1997.
72. Schena, M., Mulatero, P., Schiavone, D., Mengozzi, G., Tesio, L., Chiandussi, L., Veglio, F. Vasoactive hormones induce nitric oxide synthase mRNA expression and nitric oxide production in human endothelial cells and monocytes. Am. J. Hypertens, 1999, 12 (4 Pt 1), 388-397.
73. Marsen, T.A., Egink, G., Suckau, G., Baldamus, C.A. Tyrosine-kinase-dependent regulation of the nitric oxide synthase gene by endothelin-1 inhuman endothelial cells. Pflugers Arch., 1999, 438 (4), 538-544.
74. Goligorsky, M.S., Tsukahara, H., Magazine, H., Andersen, T.T., Malik, A.B., Bahou, W.F. Termination of endothelin signaling: Role of nitric oxide. J. Cell Physiol., 1994, 158 (3), 485-494.
75. Jiang, Z.Y., Zhou, Q.L., Chatterjee, A., Feener, E.P., Myers, M.G. Jr., White, M.F., King, G.L. Endothelin-1 modulates insulin signaling through phosphatidylinositol 3-kinase pathway in vascular smooth muscle cells. Diabetes, 1999, 48 (5), 1120-1130.
76. Bailey, C.J., Turner, R.C. Metformin. N. Engl. J. Med., 1996, 334 (9), 574-579.
77. Cigolini, M., Bosello, O., Zancanaro, C., Orlandi, P.G., Fezzi, O., Smith, U. Influence of metformin on metabolic effect of insulin in human adipose tissue in vitro. Diabete Metab., 1984, 10 (5), 311-315.
78. Matthaei, S., Hamann, A., Klein, H.H., Benecke, H., Kreymann, G., Flier, J.S., Greten, H. Association of Metformin's effect to increase insulin-stimulated glucose transport with potentiation of insulin-induced translocation of glucose transporters from intracellular pool to plasma membrane in rat adipocytes. Diabetes, 1991, 40 (7), 850-857.
79. Matthaei, S., Reibold, J.P., Hamann, A., Benecke, H., Haring, H.U., Greten, H., Klein, H.H. In vivo metformin treatment ameliorates insulin resistance: Evidence for potentiation of insulin-induced translocation and increased functional activity of glucose transporters in obese (fa/fa) Zucker rat adipocytes. Endocrinology, 1993, 133 (1), 304-311.
80. Hundal, H.S., Ramlal, T., Reyes, R., Leiter, L.A., Klip, A. Cellular mechanism of metformin action involves glucose transporter translocation from an intracellular pool to the plasma membrane in L6 muscle cells. Endocrinology, 1992, 131 (3), 1165-1173.
81. Hamann, A., Benecke, H., Greten, H., Matthaei, S. Metformin increases glucose transporter protein and gene expression in human fibroblasts. Biochem. Biophys. Res. Commun., 1993, 196 (1), 382-387.
82. Galuska, D., Zierath, J., Thorne, A., Sonnenfeld, T., Wallberg-Henriksson, H. Metformin increases insulin-stimulated glucose transport in insulin-resistant human skeletal muscle. Diabete Metab., 1991, 17 (1 Pt 2), 159-163.
83. Kennedy, J.W., Hirshman, M.F., Gervino, E.V., Ocel, J.V., Forse, R.A., Hoenig, S.J., Aronson, D., Goodyear, L.J., Horton, E.S. Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes. Diabetes, 1999, 48 (5), 1192-1197.
84. Kurth-Kraczek, E.J., Hirshman, M.F., Goodyear, L.J., Winder, W.W. 5′ AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes, 1999, 48 (8), 1667-1671.
85. Hayashi, T., Hirshman, M.F., Kurth, E.J., Winder, W.W., Goodyear, L.J. Evidence for 5′ AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes, 1998, 47 (8), 1369-1373.
86. Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., Musi, N., Hirshman, M.F., Goodyear, L.J., Moller, D.E. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest., 2001, 108 (8), 1167-1174.
87. Musi, N., Hirshman, M.F., Nygren, J., Svanfeldt, M., Bavenholm, P., Rooyackers, O., Zhou, G., Williamson, J.M., Ljunqvist, O., Efendic, S., Moller, D.E., Thorell, A., Goodyear, L.J. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes, 2002, 51 (7), 2074-2081.
88. Merrill, G.F., Kurth, E.J., Hardie, D.G., Winder, W.W. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am. J. Physiol., 1997, 273 (6 Pt 1), E1107-1112.
89. Katakam, P.V., Pollock, J.S., Pollock, D.M., Ujhelyi, M.R., Miller, A.W. Enhanced endothelin-1 response and receptor expression in small mesenteric arteries of insulin-resistant rats. Am. J. Physiol. Heart Circ. Physiol., 2001, 280 (2), H522-527.
90. Katakam, P.V., Ujhelyi, M.R., Miller, A.W. EDHF-mediated relaxation is impaired in fructose-fed rats. J. Cardiovasc. Pharmacol., 1999, 34 (3), 461-467.
91. Miller, A.W., Katakam, P.V., Ujhelyi, M.R. Impaired endothelium-mediated relaxation in coronary arteries from insulin-resistant rats. J. Vasc Res., 1999, 36 (5), 385-392.
92. Katakam, P.V., Ujhelyi, M.R., Hoenig, M.E., Miller, A.W. Endothelial dysfunction precedes hypertension in diet-induced insulin resistance. Am. J. Physiol., 1998, 275 (3 Pt 2), R788-792.
93. Baron, A.D., Zhu, J.S., Marshall, S., Irsula, O., Brechtel, G., Keech, C. Insulin resistance after hypertension induced by the nitric oxide synthesis inhibitor L-NMMA in rats. Am. J. Physiol., 1995, 269 (4 Pt 1), E709-715.
94. Shankar, R.R., Wu, Y., Shen, H.Q., Zhu, J.S., Baron, A.D. Mice with gene disruption of both endothelial and neuronal nitric oxide synthase exhibit insulin resistance. Diabetes, 2000, 49 (5), 684-687.
95. Duplain, H., Burcelin, R., Sartori, C., Cook, S., Egli, M., Lepori, M., Vollenweider, P., Pedrazzini, T., Nicod, P., Thorens, B., Scherrer, U. Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase. Circulation, 2001, 104 (3), 342-345.
96. Fang, T.C., Wu, C.C., Huang, W.C. Inhibition of nitric oxide synthesis accentuates blood pressure elevation in hyperinsulinemic rats. J. Hypertens, 2001, 19 (7), 1255-1262.
97. Koschinsky, T., Bunting, C.E., Rutter, R., Gries, F.A. Influence of metformin on vascular proliferation. Diabete Metab., 1988, 14, 566-570.
98. Bhalla, R.C., Toth, K.F., Tan, E., Bhatty, R.A., Mathias, E. Sharma, R.V. Vascular effects of metformin. Possible mechanisms for its antihypertensive action in the spontaneously hypertensive rat. Am. J. Hypertens, 1996, 9 (6), 570-576.
99. Dominguez, L.J., Davidoff, A.J., Srinivas, P.R., Standley, P.R., Walsh, M.F., Sowers, J.R. Effects of metformin on tyrosine kinase activity, glucose transport, and intracellular calcium in rat vascular smooth muscle. Endocrinology, 1996, 137 (1), 113-121.
100. Nakamura, Y., Ohya, Y., Onaka, U., Fujii, K., Abe, I., Fujishima, M. Inhibitory action of insulin-sensitizing agents on calcium channels in smooth muscle cells from resistance arteries of guinea-pig. Br. J. Pharmacol., 1998, 123 (4), 675-682.
101. Bouskela, E., Cyrino, F.Z., Wiernsperger, N. Effects of insulin and the combination of insulin plus metformin (glucophage) on microvascular reactivity in control and diabetic hamsters. Angiology, 1997, 48 (6), 503-514.
102. Chen, X.L., Panek, K., Rembold, C.M. Metformin relaxes rat tail artery by repolarization and resultant decreases in Ca2+ influx and intracellular [Ca2+]. J. Hypertens, 1997, 15 (3), 269-274.
103. Cantin, B., Zhu, D., Wen, P., Panchal, S.N., Dai, X., Gwathmey, J.K., Reaven, G.M., Valantine, H.A. Reversal of diabetes-induced rat graft transplant coronary artery disease by metformin. J. Heart Lung. Transplant, 2002, 21 (6), 637-643.
104. Hoang, K., Chen, Y.D., Reaven, G., Zhang, L., Ross, H., Billingham, M., Valantine, H. Diabetes and dyslipidemia. A new model for transplant coronary artery disease. Circulation, 1998, 97 (21), 2160-2168.
105. Verma, S., Bhanot, S., McNeill, J.H. Decreased vascular reactivity in metformin-treated fructose-hypertensive rats. Metabolism, 1996, 45 (9), 1053-1055.
106. Verma, S., Yao, L., Dumont, A.S., McNeill, J.H. Metformin treatment corrects vascular insulin resistance in hypertension. J. Hypertens, 2000, 18 (10), 1445-1450.
107. Katakam, P.V., Ujhelyi, M.R., Hoenig, M., Miller, A.W. Metformin improves vascular function in insulin-resistant rats. Hypertension, 2000, 35 (1 Pt 1), 108-112.
108. Grant, P.J. The effects of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type II diabetes. Diabetes Care, 1996, 19 (1), 64-66.
109. Velazquez, E.M., Mendoza, S.G., Wang, P., Glueck, C.J. Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome. Metabolism, 1997, 46 (4), 454-457.
110. Montanari, G., Bondioli, A., Rizzato, G., Puttini, M., Tremoli, E., Mussoni, L., Mannucci, L., Pazzucconi, F., Sirtori, C.R. Treatment with low dose metformin in patients with peripheral vascular disease. Pharmacol. Res., 1992, 25 (1), 63-73.
111. Hadigan, C., Meigs, J.B., Rabe, J., D'Agostino, R.B., Wilson, P.W., Lipinska, I., Tofler, G.H., Grinspoon, S.S. Increased PAI-1 and tPA antigen levels are reduced with metformin therapy in HIV-infected patients with fat redistribution and insulin resistance. J. Clin. Endocrinol. Metab., 2001, 86 (2), 939-943.
112. Charles, M.A., Morange, P., Eschwege, E., Andre, P., Vague, P., Juhan-Vague, I. Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects: The BIGPRO1 Study. Biguanides and the Prevention of the Risk of Obesity. Diabetes Care, 1998, 21 (11), 1967-1972.
113. Janka, H.U. Platelet and endothelial function tests during merformin treatment in diabetes mellitus (short communication). Horm. Metab. Res. Suppl., 1985, 15, 120-122.
114. Diamanti-Kandarakis, E., Spina, G., Kouli, C., Migdalis, I. Increased endothelin-1 levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy. J. Clin. Endocrinol. Metab., 2001, 86 (10), 4666-4673.
115. Sirtori, C.R., Franceschini, G., Gianfranceschi, G., Sirtori, M., Montanari, G., Bosisio, E., Mantero, E., Bondioli, A. Metformin improves peripheral vascular flow in nonhyperlipidemic patients with arterial disease. J. Cardiovasc. Pharmacol., 1984, 6 (5), 914-923.
116. Marfella, R., Acampora, R., Verrazzo, G., Ziccardi, P., De Rosa, N., Giunta, R., Giugliano, D. Metformin improves hemodynamic and theological responses to L-arginine in NIDDM patients. Diabetes Care, 1996, 19 (9), 934-939.
117. Faure, P., Rossini, E., Wiernsperger, N., Richard, M.J., Favier, A., Halimi, S. An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats. Diabetes, 1999, 48 (2), 353-357.
118. Hsueh, W.A., Law, R.E. Pharmacological treatment and mechanisms of insulin resistance. Impact on vascular smooth muscle cells, blood pressure, and lipids. Ann. N. Y. Acad. Sci., 1997, 827, 170-177.
119. Kato, K., Satoh, H., Endo, Y., Yamada, D., Midorikawa, S., Sato, W., Mizuno, K., Fujita, T., Tsukamoto, K., Watanabe, T. Thiazolidinediones down-regulate plasminogen activator inhibitor type 1 expression in human vascular endothelial cells: A possible role for PPARgamma in endothelial function. Biochem. Biophys. Res. Commun., 1999, 258 (2), 431-435.
120. Sung, B.H., Izzo, J.L. Jr., Dandona, P., Wilson, M.F. Vasodilatory effects of troglitazone improve blood pressure at rest and during mental stress in type 2 diabetes mellitus. Hypertension, 1999, 34 (1), 83-88.
121. Ogihara, T., Rakugi, H., Mikami, H., Masuo, K. Enhancement of insulin sensitivity by troglitazone lowers blood pressure in diabetic hypertensives. American Journal of Hypertension, 1995, 8, 316-320.
122. Walker, A.B., Chattington, P.D., Buckingham, R.E., Williams, G. The thiazolidinedione rosiglitazone (BRL-49653) lowers blood pressure and protects against impairment of endothelial function in Zucker fatty rats. Diabetes, 1999, 48 (7), 1448-1453.
123. Satoh, H., Tsukamoto, K., Hashimoto, Y., Hashimoto, N., Togo, M., Hara, M., Maekawa, H., Isoo, N., Kimura, S., Watanabe, T. Thiazolidinediones suppress endothelin-1 secretion from bovine vascular endothelial cells: A new possible role of PPARgamma on vascular endothelial function. Biochem. Biophys. Res. Commun., 1999, 254 (3), 757-763.
124. Yoshimoto, T., Naruse, M., Shizume, H., Naruse, K., Tanabe, A., Tanaka, M., Tago, K., Irie, K., Muraki, T., Demura, H., Zardi, L. Vasculo-protective effects of insulin sensitizing agent pioglitazone in neointimal thickening and hypertensive vascular hypertrophy. Atherosclerosis, 1999, 145 (2), 333-340.
125. Fujishima, S., Ohya, Y., Nakamura, Y., Onaka, U., Abe, I., Fujishima, M. Troglitazone, an insulin sensitizer, increases forearm blood flow in humans. Am. J. Hypertens, 1998, 11 (9), 1134-1137.
126. Hattori, Y., Hattori, S., Kasai, K. Troglitazone upregulates nitric oxide synthesis in vascular smooth muscle cells. Hypertension, 1999, 33 (4), 943-948.
127. Sekiya, M., Suzuki, J., Watanabe, K., Funada, J., Otani, T., Akutsu, H. Beneficial effect of troglitazone, an insulin-sensitizing antidiabetic agent, on coronary circulation in patients with non-insulin-dependent diabetes mellitus. Jpn. Circ. J., 2001, 65 (6), 487-490.
128. Watanabe, Y., Sunayama, S., Shimada, K., Sawano, M., Hoshi, S., Iwama, Y., Mokuno, H., Daida, H., Yamaguchi, H. Troglitazone improves endothelial dysfunction in patients with insulin resistance. J. Atheroscler Thromb., 2000, 7 (3), 159-163.