Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Rối loạn chức năng nội mô và bệnh tiểu đường: vai trò của tăng đường huyết, suy giảm tín hiệu insulin và béo phì
Tóm tắt
Rối loạn chức năng nội mô bao gồm một số thay đổi chức năng trong nội mô mạch máu liên quan đến bệnh tiểu đường và bệnh tim mạch, bao gồm những thay đổi trong điều hòa mạch máu, tăng cường sản sinh các gốc tự do oxy, kích hoạt viêm và thay đổi chức năng hàng rào. Tăng đường huyết là đặc điểm nổi bật của bệnh tiểu đường loại 1 và loại 2 và đóng vai trò quan trọng trong các biến chứng vi mạch liên quan đến bệnh tiểu đường. Mặc dù tăng đường huyết cũng đóng góp vào sự xuất hiện và tiến triển của bệnh vi mạch (nguyên nhân chính gây tử vong ở bệnh tiểu đường loại 2), các yếu tố khác như rối loạn lipid máu, tăng insulin trong máu và các yếu tố phát sinh từ mô mỡ đóng vai trò quan trọng hơn. Sự tương tác lẫn nhau giữa các yếu tố này và rối loạn chức năng nội mô xảy ra trong quá trình tiến triển của bệnh. Chúng tôi đặc biệt chú ý đến khả năng tham gia của stress lưới nội (stress ER) và vai trò của béo phì cùng với các adipokine phát sinh từ mô mỡ như là những yếu tố góp phần vào rối loạn chức năng nội mô trong bệnh tiểu đường loại 2. Sự tương tác gần gũi của các tế bào mỡ của mô mỡ xung quanh mạch với các động mạch và tiểu động mạch tạo điều kiện cho sự tiếp xúc của tế bào nội mô với các adipokine, đặc biệt khi viêm kích hoạt mô mỡ, từ đó ảnh hưởng đến điều hòa mạch và sự thu hút mao mạch trong cơ. Do đó, sự rối loạn chức năng ban đầu của tế bào nội mô là nền tảng cho những thay đổi chuyển hóa và mạch máu góp phần vào sự phát triển của bệnh tiểu đường loại 2.
Từ khóa
#rối loạn chức năng nội mô #bệnh tiểu đường #tăng đường huyết #rối loạn tín hiệu insulin #béo phìTài liệu tham khảo
Adams TD, Gress RE, Smith SC, Halverson RC, Simper SC, Rosamond WD, LaMonte MJ, Stroup AM, Hunt SC (2007) Long-term mortality after gastric bypass surgery. N Engl J Med 357:753–761
Aiello LP (2005) Angiogenic pathways in diabetic retinopathy. N Engl J Med 353:839–841
Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487
Aird WC (2007a) Phenotypic heterogeneity of the endothelium. I. Structure, function, and mechanisms. Circ Res 100:158–173
Aird WC (2007b) Phenotypic heterogeneity of the endothelium. II. Representative vascular beds. Circ Res 100:174–190
Aizawa-Abe M, Ogawa Y, Masuzaki H, Ebihara K, Satoh N, Iwai H, Matsuoka N, Hayashi T, Hosoda K, Inoue G, Yoshimasa Y, Nakao K (2000) Pathophysiological role of leptin in obesity-related hypertension. J Clin Invest 105:1243–1252
Al Suwaidi J, Higano ST, Holmes DR, Lennon R, Lerman A (2001) Obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries. J Am Coll Cardiol 37:1523–1528
Alessi MC, Juhan-Vague I (2008) Metabolic syndrome, haemostasis and thrombosis. Thromb Haemost 99:995–1000
American Diabetes Association (2005) Standards of medical care in diabetes. Diabetes Care 28:S4–36
Andreoli CM, Miller JW (2007) Anti-vascular endothelial growth factor therapy for ocular neovascular disease. Curr Opin Ophthalmol 18:502–508
Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa Ji, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257:79–83
Austin RC, Lentz SR, Werstuck GH (2004) Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease. Cell Death Differ 1 (11 Suppl):S56–S64
Bagi Z, Koller A, Kaley G (2003) Superoxide-NO interaction decreases flow- and agonist-induced dilations of coronary arterioles in type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol 285:H1404–H1410
Bakker W, Sipkema P, Stehouwer CD, Serne EH, Smulders YM, Hinsbergh VW van, Eringa EC (2008) Protein kinase C theta activation induces insulin-mediated constriction of muscle resistance arteries. Diabetes 57:706–713
Becker A, Hinsbergh VW van, Jager A, Kostense PJ, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD (2002) Why is soluble intercellular adhesion molecule-1 related to cardiovascular mortality? Eur J Clin Invest 32:1–8
Beltowski J, Wojcicka G, Jamroz A (2003) Stimulatory effect of leptin on nitric oxide production is impaired in dietary-induced obesity. Obes Res 11:1571–1580
Berg BM van den, Nieuwdorp M, Stroes ES, Vink H (2006) Glycocalyx and endothelial (dys) function: from mice to men. Pharmacol Rep 58 (Suppl):75–80
Bergholm R, Tiikkainen M, Vehkavaara S, Tamminen M, Teramo K, Rissanen A, Yki-Jarvinen H (2003) Lowering of LDL cholesterol rather than moderate weight loss improves endothelium-dependent vasodilatation in obese women with previous gestational diabetes. Diabetes Care 26:1667–1672
Berkowitz DE, White R, Li D, Minhas KM, Cernetich A, Kim S, Burke S, Shoukas AA, Nyhan D, Champion HC, Hare JM (2003) Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation 108:2000–2006
Beyer AM, Baumbach GL, Halabi CM, Modrick ML, Lynch CM, Gerhold TD, Ghoneim SM, Lange WJ de, Keen HL, Tsai YS, Maeda N, Sigmund CD, Faraci FM (2008) Interference with PPAR{gamma} signaling causes cerebral vascular dysfunction, hypertrophy, and remodeling. Hypertension 51:867–871
Bornstein SR, Abu-Asab M, Glasow A, Path G, Hauner H, Tsokos M, Chrousos GP, Scherbaum WA (2000) Immunohistochemical and ultrastructural localization of leptin and leptin receptor in human white adipose tissue and differentiating human adipose cells in primary culture. Diabetes 49:532–538
Bottaro DP, Bonner-Weir S, King GL (1989) Insulin receptor recycling in vascular endothelial cells. Regulation by insulin and phorbol ester. J Biol Chem 264:5916–5923
Bouloumie A, Drexler HCA, Lafontan M, Busse R (1998) Leptin, the product of Ob gene, promotes angiogenesis. Circ Res 83:1059–1066
Brook RD, Bard RL, Rubenfire M, Ridker PM, Rajagopalan S (2001) Usefulness of visceral obesity (waist/hip ratio) in predicting vascular endothelial function in healthy overweight adults. Am J Cardiol 88:1264–1269
Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820
Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625
Caballero AE, Arora S, Saouaf R, Lim SC, Smakowski P, Park JY, King GL, LoGerfo FW, Horton ES, Veves A (1999) Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes 48:1856–1862
Caballero AE, Delgado A, Aguilar-Salinas CA, Herrera AN, Castillo JL, Cabrera T, Gomez-Perez FJ, Rull JA (2004) The differential effects of metformin on markers of endothelial activation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled, randomized clinical trial. J Clin Endocrinol Metab 89:3943–3948
Cai WJ, Koltai S, Kocsis E, Scholz D, Kostin S, Luo X, Schaper W, Schaper J (2003) Remodeling of the adventitia during coronary arteriogenesis. Am J Physiol Heart Circ Physiol 284:H31–H40
Caporali A, Pani E, Horrevoets AJ, Kraenkel N, Oikawa A, Sala-Newby GB, Meloni M, Cristofaro B, Graiani G, Leroyer AS, Boulanger CM, Spinetti G, Yoon SO, Madeddu P, Emanueli C (2008) Neurotrophin p75 receptor (p75NTR) promotes endothelial cell apoptosis and inhibits angiogenesis: implications for diabetes-induced impaired neovascularization in ischemic limb muscles. Circ Res 103:e15–e26
Cardillo C, Nambi SS, Kilcoyne CM, Choucair WK, Katz A, Quon MJ, Panza JA (1999) Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation 100:820–825
Cardillo C, Campia U, Iantorno M, Panza JA (2004) Enhanced vascular activity of endogenous endothelin-1 in obese hypertensive patients. Hypertension 43:36–40
Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438:932–936
Castillo C, Bogardus C, Bergman R, Thuillez P, Lillioja S (1994) Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men. J Clin Invest 93:10–16
Ceradini DJ, Yao D, Grogan RH, Callaghan MJ, Edelstein D, Brownlee M, Gurtner GC (2008) Decreasing intracellular superoxide corrects defective ischemia-induced new vessel formation in diabetic mice. J Biol Chem 283:10930–10938
Cersosimo E, DeFronzo RA (2006) Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes Metab Res Rev 22:423–436
Chen H, Montagnani M, Funahashi T, Shimomura I, Quon MJ (2003) Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem 278:45021–45026
Chen K, Li F, Li J, Cai H, Strom S, Bisello A, Kelley DE, Friedman-Einat M, Skibinski GA, McCrory MA, Szalai AJ, Zhao AZ (2006) Induction of leptin resistance through direct interaction of C-reactive protein with leptin. Nat Med 12:425–432
Chen S, Hong SW, Iglesias-de la Cruz MC, Isono M, Casaretto A, Ziyadeh FN (2001) The key role of the transforming growth factor-beta system in the pathogenesis of diabetic nephropathy. Ren Fail 23:471–481
Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM (1998) Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91:3527–3561
Clark MG, Wallis MG, Barrett EJ, Vincent MA, Richards SM, Clerk LH, Rattigan S (2003) Blood flow and muscle metabolism: a focus on insulin action. Am J Physiol Endocrinol Metab 284:E241–E258
Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougneres P, Lebouc Y, Froguel P, Guy-Grand B (1998) A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392:398–401
Clerk LH, Rattigan S, Clark MG (2002) Lipid infusion impairs physiologic insulin-mediated capillary recruitment and muscle glucose uptake in vivo. Diabetes 51:1138–1145
Cock TA, Houten SM, Auwerx J (2004) Peroxisome proliferator-activated receptor-{gamma}: too much of a good thing causes harm. EMBO Reports 5:142–147
Coleman DL (1979) Obesity genes: beneficial effects in heterozygous mice. Science 203:663–665
Combs TP, Wagner JA, Berger J, Doebber T, Wang WJ, Zhang BB, Tanen M, Berg AH, O’Rahilly S, Savage DB, Chatterjee K, Weiss S, Larson PJ, Gottesdiener KM, Gertz BJ, Charron MJ, Scherer PE, Moller DE (2002) Induction of adipocyte complement-related protein of 30 kilodaltons by PPAR{gamma} agonists: a potential mechanism of insulin sensitization. Endocrinology 143:998–1007
Coppack SW (2001) Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc 60:349–356
Correia ML, Haynes WG, Rahmouni K, Morgan DA, Sivitz WI, Mark AL (2002) The concept of selective leptin resistance: evidence from agouti yellow obese mice. Diabetes 51:439–442
Costa J, Borges M, David C, Vaz Carneiro A (2006) Efficacy of lipid lowering drug treatment for diabetic and non-diabetic patients: meta-analysis of randomised controlled trials. BMJ 332:1115–1124
Cybulsky MI, Gimbrone MA Jr (1991) Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 251:788–791
D’Amico G, Bazzi C (2003) Pathophysiology of proteinuria. Kidney Int 63:809–825
Date H, Imamura T, Ideguchi T, Kawagoe J, Sumi T, Masuyama H, Onitsuka H, Ishikawa T, Nagoshi T, Eto T (2006) Adiponectin produced in coronary circulation regulates coronary flow reserve in nondiabetic patients with angiographically normal coronary arteries. Clin Cardiol 29:211–214
Davda RK, Stepniakowski KT, Lu G, Ullian ME, Goodfriend TL, Egan BM (1995) Oleic acid inhibits endothelial nitric oxide synthase by a protein kinase C-independent mechanism. Hypertension 26:764–770
De Vriese AS, Verbeuren TJ, Van de Voorde J, Lameire NH, Vanhoutte PM (2000) Endothelial dysfunction in diabetes. Br J Pharmacol 130:963–974
Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A (1989) Albuminuria reflects widespread vascular damage. The steno hypothesis. Diabetologia 32:219–226
DeFronzo RA (1988) Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37:667–687
DeFronzo RA, Bonadonna RC, Ferrannini E (1992) Pathogenesis of NIDDM. A balanced overview. Diabetes Care 15:318–368
Dekker RJ, Thienen JV van, Rohlena J, Jager SC de, Elderkamp YW, Seppen J, Vries CJ de, Biessen EA, Berkel TJ van, Pannekoek H, Horrevoets AJ (2005) Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes. Am J Pathol 167:609–618
Dickhout JG, Hossain GS, Pozza LM, Zhou J, Lhotak S, Austin RC (2005) Peroxynitrite causes endoplasmic reticulum stress and apoptosis in human vascular endothelium: implications in atherogenesis. Arterioscler Thromb Vasc Biol 25:2623–2629
Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, Wu J, Brownlee M (2000) Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci USA 97:12222–12226
Dworakowski R, Alom-Ruiz SP, Shah AM (2008) NADPH oxidase-derived reactive oxygen species in the regulation of endothelial phenotype. Pharmacol Rep 60:21–28
Egashira K, Hirooka Y, Kai H, Sugimachi M, Suzuki S, Inou T, Takeshita A (1994) Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Circulation 89:2519–2524
Eizirik DL, Cardozo AK, Cnop M (2008) The role for endoplasmic reticulum stress in diabetes mellitus. Endocr Rev 29:42–61
Engerman RL, Kern TS (1987) Progression of incipient diabetic retinopathy during good glycemic control. Diabetes 36:808–812
Erdei N, Toth A, Pasztor ET, Papp Z, Edes I, Koller A, Bagi Z (2006) High-fat diet-induced reduction in nitric oxide-dependent arteriolar dilation in rats: role of xanthine oxidase-derived superoxide anion. Am J Physiol Heart Circ Physiol 291:H2107–H2115
Eringa EC, Stehouwer CDA, Walburg K, Clark AD, Nieuw Amerongen GP, Westerhof N, Sipkema P (2006) Physiological concentrations of insulin induce endothelin-dependent vasoconstriction of skeletal muscle resistance arteries in the presence of tumor necrosis factor-{alpha} dependence on c-jun n-terminal kinase. Arterioscler Thromb Vasc Biol 26:274–280
Eringa EC, Stehouwer CDA, Roos MH, Westerhof N, Sipkema P (2007) Selective resistance to vasoactive effects of insulin in muscle resistance arteries of obese Zucker (fa/fa) rats. Am J Physiol Endocrinol Metab 293:E1134–E1139
Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, Giugliano D (2003) Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289:1799–1804
Fa ML, Schalkwijk CG, Engelse M, Hinsbergh VW van (2006) Interaction of Nepsilon(carboxymethyl)lysine- and methylglyoxal-modified albumin with endothelial cells and macrophages. Splice variants of RAGE may limit the responsiveness of human endothelial cells to AGEs. Thromb Haemost 95:320–328
Fioretto P, Steffes MW, Sutherland DE, Goetz FC, Mauer M (1998) Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 339:69–75
Fitzgerald SM, Kemp-Harper BK, Parkington HC, Head GA, Evans RG (2007) Endothelial dysfunction and arterial pressure regulation during early diabetes in mice: roles for nitric oxide and endothelium-derived hyperpolarizing factor. Am J Physiol Regul Integr Comp Physiol 293:R707–R713
Forbes JM, Coughlan MT, Cooper ME (2008) Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes 57:1446–1454
Galili O, Versari D, Sattler KJ, Olson ML, Mannheim D, McConnell JP, Chade AR, Lerman LO, Lerman A (2007) Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress. Am J Physiol Heart Circ Physiol 292:H904–H911
Gharavi NM, Gargalovic PS, Chang I, Araujo JA, Clark MJ, Szeto WL, Watson AD, Lusis AJ, Berliner JA (2007) High-density lipoprotein modulates oxidized phospholipid signaling in human endothelial cells from proinflammatory to anti-inflammatory. Arterioscler Thromb Vasc Biol 27:1346–1353
Gimbrone MA Jr (1999) Endothelial dysfunction, hemodynamic forces, and atherosclerosis. Thromb Haemost 82:722–726
Goldfine AB, Beckman JA, Betensky RA, Devlin H, Hurley S, Varo N, Schonbeck U, Patti ME, Creager MA (2006) Family history of diabetes is a major determinant of endothelial function. J Am Coll Cardiol 47:2456–2461
Gollasch M, Dubrovska G (2004) Paracrine role for periadventitial adipose tissue in the regulation of arterial tone. Trends Pharmacol Sci 25:647–653
Goodpaster BH, Wolf D (2004) Skeletal muscle lipid accumulation in obesity, insulin resistance, and type 2 diabetes. Pediatr Diabetes 5:219–226
Goto H, Nishikawa T, Sonoda K, Kondo T, Kukidome D, Fujisawa K, Yamashiro T, Motoshima H, Matsumura T, Tsuruzoe K, Araki E (2008) Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice. Biochem Biophys Res Commun 366:814–820
Gudbjornsdottir S, Elam M, Sellgren J, Anderson EA (1996) Insulin increases forearm vascular resistance in obese, insulin-resistant hypertensives. J Hypertens 14:91–97
Haaren PM van, VanBavel E, Vink H, Spaan JA (2003) Localization of the permeability barrier to solutes in isolated arteries by confocal microscopy. Am J Physiol Heart Circ Physiol 285:H2848–H2856
Hagenfeldt L, Dahlquist G, Persson B (1989) Plasma amino acids in relation to metabolic control in insulin-dependent diabetic children. Acta Paediatr Scand 78:278–282
Hammes HP, Du X, Edelstein D, Taguchi T, Matsumura T, Ju Q, Lin J, Bierhaus A, Nawroth P, Hannak D, Neumaier M, Bergfeld R, Giardino I, Brownlee M (2003) Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med 9:294–299
Hart GW, Housley MP, Slawson C (2007) Cycling of O-linked [beta]-N-acetylglucosamine on nucleocytoplasmic proteins. Nature 446:1017–1022
Harte AL, McTernan PG, McTernan CL, Crocker J, Starcynski J, Barnett AH, Matyka K, Kumar S (2003a) Insulin increases angiotensinogen expression in human abdominal subcutaneous adipocytes. Diabetes Obes Metab 5:462–467
Harte AL, McTernan PG, McTernan CL, Smith SA, Barnett AH, Kumar S (2003b) Rosiglitazone inhibits the insulin-mediated increase in PAI-1 secretion in human abdominal subcutaneous adipocytes. Diabetes Obes Metab 5:302–310
Hattori Y, Suzuki M, Hattori S, Kasai K (2003) Globular adiponectin upregulates nitric oxide production in vascular endothelial cells. Diabetologia 46:1543–1549
Hauner H (2004) The new concept of adipose tissue function. Physiol Behav 83:653–658
Heickendorff L, Ledet T, Rasmussen LM (1994) Glycosaminoglycans in the human aorta in diabetes mellitus: a study of tunica media from areas with and without atherosclerotic plaque. Diabetologia 37:286–292
Heitzer T, Krohn K, Albers S, Meinertz T (2000) Tetrahydrobiopterin improves endothelium-dependent vasodilation by increasing nitric oxide activity in patients with type II diabetes mellitus. Diabetologia 43:1435–1438
Hinsbergh VW van (2001) The endothelium: vascular control of haemostasis. Eur J Obstet Gynecol Reprod Biol 95:198–201
Hodnett BL, Hester RL (2007) Regulation of muscle blood flow in obesity. Microcirculation 14:273–288
Hogeboom van Buggenum IM, Polak BC, Reichert-Thoen JW, Vries-Knoppert WA de, Hinsbergh VW van, Tangelder GJ. (2002) Angiotensin converting enzyme inhibiting therapy is associated with lower vitreous vascular endothelial growth factor concentrations in patients with proliferative diabetic retinopathy. Diabetologia 45:203–209
Hotamisligil GS (2005) Role of endoplasmic reticulum stress and c-jun nh2-terminal kinase pathways in inflammation and origin of obesity and diabetes. Diabetes 54:S73–S78
Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91
Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95:2409–2415
Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595–1599
Hui YY, McAmis WC, Baynes JW, Schaeffer RC Jr, Wolf MB (2001) Effect of advanced glycation end products on oxidative stress in endothelial cells in culture: a warning on the use of cells studied in serum-free media. Diabetologia 44:1310–1317
Jager A, Hinsbergh VW van, Kostense PJ, Emeis JJ, Yudkin JS, Nijpels G, Dekker JM, Heine RJ, Bouter LM, Stehouwer CD (1999) von Willebrand factor, C-reactive protein, and 5-year mortality in diabetic and nondiabetic subjects: the Hoorn study. Arterioscler Thromb Vasc Biol 19:3071–3078
Jager A, Hinsbergh VW van, Kostense PJ, Emeis JJ, Nijpels G, Dekker JM, Heine RJ, Bouter LM, Stehouwer CD (2000) Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study. Diabetes 49:485–491
Jensen JS, Borch-Johnsen K, Jensen G, Feldt-Rasmussen B (1995) Microalbuminuria reflects a generalized transvascular albumin leakiness in clinically healthy subjects. Clin Sci (Lond) 88:629–633
Jiang ZY, Lin YW, Clemont A, Feener EP, Hein KD, Igarashi M, Yamauchi T, White MF, King GL (1999) Characterization of selective resistance to insulin signaling in the vasculature of obese zucker (fa/fa) rats. J Clin Invest 104:447–457
Jongh RT de, Serne EH, IJzerman RG, Vries G de, Stehouwer CDA (2004) Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy. Diabetes 53:2873–2882
Jongh RT de, Ijzerman RG, Serne EH, Voordouw JJ, Yudkin JS, Waal HAD de, Stehouwer CDA, Weissenbruch MM van (2006) Visceral and truncal subcutaneous adipose tissue are associated with impaired capillary recruitment in healthy individuals. J Clin Endocrinol Metab 91:5100–5106
Kaesemeyer WH, Ogonowski AA, Jin L, Caldwell RB, Caldwell RW (2000) Endothelial nitric oxide synthase is a site of superoxide synthesis in endothelial cells treated with glyceryl trinitrate. Br J Pharmacol 131:1019–1023
Kim F, Gallis B, Corson MA (2001) TNF-{alpha} inhibits flow and insulin signaling leading to NO production in aortic endothelial cells. Am J Physiol Cell Physiol 280:C1057–C1065
Kim F, Tysseling KA, Rice J, Gallis B, Haji L, Giachelli CM, Raines EW, Corson MA, Schwartz MW (2005a) Activation of IKKβ by glucose is necessary and sufficient to impair insulin signaling and nitric oxide production in endothelial cells. J Mol Cell Cardiol 39:327–334
Kim F, Tysseling KA, Rice J, Pham M, Haji L, Gallis BM, Baas AS, Paramsothy P, Giachelli CM, Corson MA, Raines EW (2005b) Free fatty acid impairment of nitric oxide production in endothelial cells is mediated by IKK{beta}. Arterioscler Thromb Vasc Biol 25:989–994
Kim JK, Fillmore JJ, Sunshine MJ, Albrecht B, Higashimori T, Kim DW, Liu ZX, Soos TJ, Cline GW, O’Brien WR, Littman DR, Shulman GI (2004) PKC-{theta} knockout mice are protected from fat-induced insulin resistance. J Clin Invest 114:823–827
King GL (1996) The role of hyperglycaemia and hyperinsulinaemia in causing vascular dysfunction in diabetes. Ann Med 28:427–432
Kliewer SA, Xu HE, Lambert MH, Willson TM (2001) Peroxisome proliferator-activated receptors: from genes to physiology. Recent Prog Horm Res 56:239–265
Kobashi C, Urakaze M, Kishida M, Kibayashi E, Kobayashi H, Kihara S, Funahashi T, Takata M, Temaru R, Sato A, Yamazaki K, Nakamura N, Kobayashi M (2005) Adiponectin inhibits endothelial synthesis of interleukin-8. Circ Res 97:1245–1252
Koya D, King GL (1998) Protein kinase C activation and the development of diabetic complications. Diabetes 47:859–866
Krzyzanowska K, Mittermayer F, Wolzt M, Schernthaner G (2007) Asymmetric dimethylarginine predicts cardiovascular events in patients with type 2 diabetes. Diabetes Care 30:1834–1839
Kubota T, Kubota N, Moroi M, Terauchi Y, Kobayashi T, Kamata K, Suzuki R, Tobe K, Namiki A, Aizawa S, Nagai R, Kadowaki T, Yamaguchi T (2003) Lack of insulin receptor substrate-2 causes progressive neointima formation in response to vessel injury. Circulation 107:3073–3080
Kume N, Cybulsky MI, Gimbrone MA Jr (1992) Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest 90:1138–1144
Lajer M, Tarnow L, Jorsal A, Teerlink T, Parving HH, Rossing P (2008) Plasma concentration of asymmetric dimethylarginine (ADMA) predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy. Diabetes Care 31:747–752
Laviola L, Belsanti G, Davalli AM, Napoli R, Perrini S, Weir GC, Giorgino R, Giorgino F (2001) Effects of streptozocin diabetes and diabetes treatment by islet transplantation on in vivo insulin signaling in rat heart. Diabetes 50:2709–2720
Levy BI, Ambrosio G, Pries AR, Struijker-Boudier HAJ (2001) Microcirculation in hypertension: a new target for treatment? Circulation 104:735–740
Li G, Barrett EJ, Barrett MO, Cao W, Liu Z (2007) Tumor necrosis factor-{alpha} induces insulin resistance in endothelial cells via a p38 mitogen-activated protein kinase-dependent pathway. Endocrinology 148:3356–3363
Lieuw-a-Fa ML, Schalkwijk CG, Engelse M, Hinsbergh VW van (2006) Interaction of Nepsilon(carboxymethyl)lysine- and methylglyoxal-modified albumin with endothelial cells and macrophages. Splice variants of RAGE may limit the responsiveness of human endothelial cells to AGEs. Thromb Haemost 95:320–328
Lin KY, Ito A, Asagami T, Tsao PS, Adimoolam S, Kimoto M, Tsuji H, Reaven GM, Cooke JP (2002) Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 106:987–992
Lundman P, Tornvall P, Nilsson L, Pernow J (2001) A triglyceride-rich fat emulsion and free fatty acids but not very low density lipoproteins impair endothelium-dependent vasorelaxation. Atherosclerosis 159:35–41
Luo D, He Y, Zhang H, Yu L, Chen H, Xu Z, Tang S, Urano F, Min W (2008) AIP1 is critical in transducing IRE1-mediated endoplasmic reticulum stress response. J Biol Chem 283:11905–11912
Marshall S, Bacote V, Traxinger RR (1991) Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J Biol Chem 266:4706–4712
Martin A, Komada MR, Sane DC (2003) Abnormal angiogenesis in diabetes mellitus. Med Res Rev 23:117–145
Marx N, Bourcier T, Sukhova GK, Libby P, Plutzky J (1999) PPAR{gamma} activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPAR{gamma} as a potential mediator in vascular disease. Arterioscler Thromb Vasc Biol 19:546–551
Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, Sarov-Blat L, O’Brien S, Keiper EA, Johnson AG, Martin J, Goldstein BJ, Shi Y (2003) Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 108:2460–2466
Mazzone T, Chait A, Plutzky J (2008) Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies. Lancet 371:1800–1809
Meigs JB, Hu FB, Rifai N, Manson JE (2004) Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA 291:1978–1986
Meng QH, Jamal W, Hart SL, McEwan JR (2006) Application to vascular adventitia of a nonviral vector for TIMP-1 gene therapy to prevent intimal hyperplasia. Hum Gene Ther 17:717–727
Minokoshi Y, Kim YB, Peroni OD, Fryer LGD, Muller C, Carling D, Kahn BB (2002) Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415:339–343
Mogensen CE (1984) Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 310:356–360
Moien-Afshari F, Ghosh S, Khazaei M, Kieffer TJ, Brownsey RW, Laher I (2008) Exercise restores endothelial function independently of weight loss or hyperglycaemic status in db/db mice. Diabetologia 51:1327–1337
Montagnani M, Ravichandran LV, Chen H, Esposito DL, Quon MJ (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
Moos MP, John N, Grabner R, Nossmann S, Gunther B, Vollandt R, Funk CD, Kaiser B, Habenicht AJ (2005) The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 25:2386–2391
Munzel T, Sinning C, Post F, Warnholtz A, Schulz E (2008) Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction. Ann Med 40:180–196
Naka Y, Bucciarelli LG, Wendt T, Lee LK, Rong LL, Ramasamy R, Yan SF, Schmidt AM (2004) RAGE axis: animal models and novel insights into the vascular complications of diabetes. Arterioscler Thromb Vasc Biol 24:1342–1349
Nakagawa K, Higashi Y, Sasaki S, Oshima T, Matsuura H, Chayama K (2002) Leptin causes vasodilation in humans. Hypertens Res 25:161–165
Neel JV (1962) Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Am J Hum Genet 14:353–362
Nguyen TT, Wang JJ, Islam FMA, Mitchell P, Tapp RJ, Zimmet PZ, Simpson R, Shaw J, Wong TY (2008) Retinal arteriolar narrowing predicts incidence of diabetes: the Australian diabetes, obesity and lifestyle (AusDiab) study. Diabetes 57:536–539
Nieuwdorp M, Mooij HL, Kroon J, Atasever B, Spaan JA, Ince C, Holleman F, Diamant M, Heine RJ, Hoekstra JB, Kastelein JJ, Stroes ES, Vink H (2006a) Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes. Diabetes 55:1127–1132
Nieuwdorp M, Haeften TW van, Gouverneur MC, Mooij HL, Lieshout MH van, Levi M, Meijers JC, Holleman F, Hoekstra JB, Vink H, Kastelein JJ, Stroes ES (2006b) Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo. Diabetes 55:480–486
Noh H, King GL (2007) The role of protein kinase C activation in diabetic nephropathy. Kidney Int Suppl:S49-S53
Nosadini R, Velussi M, Brocco E, Abaterusso C, Piarulli F, Morgia G, Satta A, Faedda R, Abhyankar A, Luthman H, Tonolo G (2005) Altered transcapillary escape of albumin and microalbuminuria reflects two different pathogenetic mechanisms. Diabetes 54:228–233
Okado A, Kawasaki Y, Hasuike Y, Takahashi M, Teshima T, Fujii J, Taniguchi N (1996) Induction of apoptotic cell death by methylglyoxal and 3-deoxyglucosone in macrophage-derived cell lines. Biochem Biophys Res Commun 225:219–224
Okamoto E, Couse T, De Leon H, Vinten-Johansen J, Goodman RB, Scott NA, Wilcox JN (2001) Perivascular inflammation after balloon angioplasty of porcine coronary arteries. Circulation 104:2228–2235
Okon EB, Szado T, Laher I, McManus B, Breemen C van (2003) Augmented contractile response of vascular smooth muscle in a diabetic mouse model. J Vasc Res 40:520–530
Okon EB, Chung AWY, Rauniyar P, Padilla E, Tejerina T, McManus BM, Luo H, Breemen C van (2005) Compromised arterial function in human type 2 diabetic patients. Diabetes 54:2415–2423
Okouchi M, Okayama N, Imai S, Omi H, Shimizu M, Fukutomi T, Itoh M (2002) High insulin enhances neutrophil transendothelial migration through increasing surface expression of platelet endothelial cell adhesion molecule-1 via activation of mitogen activated protein kinase. Diabetologia 45:1449–1456
Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y (1999) Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 100:2473–2476
Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Gorgun C, Glimcher LH, Hotamisligil GS (2004) Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306:457–461
Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, Gorgun CZ, Hotamisligil GS (2006) Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313:1137–1140
Pannirselvam M, Verma S, Anderson TJ, Triggle CR (2002) Cellular basis of endothelial dysfunction in small mesenteric arteries from spontaneously diabetic (db/db -/-) mice: role of decreased tetrahydrobiopterin bioavailability. Br J Pharmacol 136:255–263
Pardridge WM, Boado RJ, Farrell CR (1990) Brain-type glucose transporter (GLUT-1) is selectively localized to the blood-brain barrier. Studies with quantitative Western blotting and in situ hybridization. J Biol Chem 265:18035–18040
Patti ME, Virkamaki A, Landaker EJ, Kahn CR, Yki-Jarvinen H (1999) Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle. Diabetes 48:1562–1571
Perticone F, Ceravolo R, Candigliota M, Ventura G, Iacopino S, Sinopoli F, Mattioli PL (2001) Obesity and body fat distribution induce endothelial dysfunction by oxidative stress: protective effect of vitamin C. Diabetes 50:159–165
Picard F, Auwerx J (2002) PPAR(gamma) and glucose homeostasis. Annu Rev Nutr 22:167–197
Pieper GM, Siebeneich W, Moore-Hilton G, Roza AM (1997) Reversal by L-arginine of a dysfunctional arginine/nitric oxide pathway in the endothelium of the genetic diabetic BB rat. Diabetologia 40:910–915
Pilz S, Horejsi R, Moller R, Almer G, Scharnagl H, Stojakovic T, Dimitrova R, Weihrauch G, Borkenstein M, Maerz W, Schauenstein K, Mangge H (2005) Early atherosclerosis in obese juveniles is associated with low serum levels of adiponectin. J Clin Endocrinol Metab 90:4792–4796
Pober JS, Sessa WC (2007) Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 7:803–815
Potenza MA, Marasciulo FL, Chieppa DM, Brigiani GS, Formoso G, Quon MJ, Montagnani M (2005) Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. Am J Physiol Heart Circ Physiol 289:H813–H822
Quehenberger P, Exner M, Sunder-Plassmann R, Ruzicka K, Bieglmayer C, Endler G, Muellner C, Speiser W, Wagner O (2002) Leptin induces endothelin-1 in endothelial cells in vitro. Circ Res 90:711–718
Rahmouni K, Mark AL, Haynes WG, Sigmund CD (2004) Adipose depot-specific modulation of angiotensinogen gene expression in diet-induced obesity. Am J Physiol Endocrinol Metab 286:E891–E895
Rahmouni K, Morgan DA, Morgan GM, Mark AL, Haynes WG (2005) Role of selective leptin resistance in diet-induced obesity hypertension. Diabetes 54:2012–2018
Raitakari M, Ilvonen T, Ahotupa M, Lehtimaki T, Harmoinen A, Suominen P, Elo J, Hartiala J, Raitakari OT (2004) Weight reduction with very-low-caloric diet and endothelial function in overweight adults: role of plasma glucose. Arterioscler Thromb Vasc Biol 24:124–128
Raman CS, Li H, Martasek P, Kral V, Masters BS, Poulos TL (1998) Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center. Cell 95:939–950
Rask-Madsen C, King GL (2007) Mechanisms of disease: endothelial dysfunction in insulin resistance and diabetes. Nat Clin Pract Endocrinol Metab 3:46–56
Ratcliffe PJ (2006) Understanding hypoxia signalling in cells—a new therapeutic opportunity? Clin Med 6:573–578
Reaven GM (1995) Pathophysiology of insulin resistance in human disease. Physiol Rev 75:473–486
Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, Pell CL, Johnstone BH, Considine RV, March KL (2004) Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 109:1292–1298
Rey FE, Li XC, Carretero OA, Garvin JL, Pagano PJ (2002) Perivascular superoxide anion contributes to impairment of endothelium-dependent relaxation: role of gp91(phox). Circulation 106:2497–2502
Ridker PM (2007) Inflammatory biomarkers and risks of myocardial infarction, stroke, diabetes, and total mortality: implications for longevity. Nutr Rev 65:S253–S259
Romero MJ, Platt DH, Tawfik HE, Labazi M, El Remessy AB, Bartoli M, Caldwell RB, Caldwell RW (2008) Diabetes-induced coronary vascular dysfunction involves increased arginase activity. Circ Res 102:95–102
Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340:115–126
Ross RM, Kolka CM, Rattigan S, Clark MG (2007) Acute blockade by endothelin-1 of haemodynamic insulin action in rats. Diabetologia 50:443–451
Roy S, Sala R, Cagliero E, Lorenzi M (1990) Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory. Proc Natl Acad Sci USA 87:404–408
Saraswathi V, Hasty AH (2006) The role of lipolysis in mediating the proinflammatory effects of very low density lipoproteins in mouse peritoneal macrophages. J Lipid Res 47:1406–1415
Sasaki S, Higashi Y, Nakagawa K, Kimura M, Noma K, Sasaki S, Hara K, Matsuura H, Goto C, Oshima T, Chayama K (2002) A low-calorie diet improves endothelium-dependent vasodilation in obese patients with essential hypertension. Am J Hypertens 15:302–309
Sasso FC, Torella D, Carbonara O, Ellison GM, Torella M, Scardone M, Marra C, Nasti R, Marfella R, Cozzolino D, Indolfi C, Cotrufo M, Torella R, Salvatore T (2005) Increased vascular endothelial growth factor expression but impaired vascular endothelial growth factor receptor signaling in the myocardium of type 2 diabetic patients with chronic coronary heart disease. J Am Coll Cardiol 46:827–834
Sayeski PP, Kudlow JE (1996) Glucose metabolism to glucosamine is necessary for glucose stimulation of transforming growth factor-alpha gene transcription. J Biol Chem 271:15237–15243
Schalkwijk CG, Poland DC, Dijk W van, Kok A, Emeis JJ, Drager AM, Doni A, Hinsbergh VW van, Stehouwer CD (1999) Plasma concentration of C-reactive protein is increased in type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation. Diabetologia 42:351–357
Schalkwijk CG, Bezu J van, Schors RC van der, Uchida K, Stehouwer CDA, Hinsbergh VWM van (2006) Heat-shock protein 27 is a major methylglyoxal-modified protein in endothelial cells. FEBS Lett 580:1565–1570
Schernthaner G, Morton JM (2008) Bariatric surgery in patients with morbid obesity and type 2 diabetes. Diabetes Care 31:S297–S302
Schmidt HH, Hofmann H, Schindler U, Shutenko ZS, Cunningham DD, Feelisch M (1996) No.NO from NO synthase. Proc Natl Acad Sci USA 93:14492–14497
Schnitzer JE, Oh P, Pinney E, Allard J (1994) Filipin-sensitive caveolae-mediated transport in endothelium: reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules. J Cell Biol 127:1217–1232
Schoeller DA, Buchholz AC (2005) Energetics of obesity and weight control: does diet composition matter? J Am Diet Assoc 105:24–28
Schroeder CA Jr, Chen YL, Messina EJ (1999) Inhibition of NO synthesis or endothelium removal reveals a vasoconstrictor effect of insulin on isolated arterioles. Am J Physiol 276:815–820
Sciacqua A, Candigliota M, Ceravolo R, Scozzafava A, Sinopoli F, Corsonello A, Sesti G, Perticone F (2003) Weight loss in combination with physical activity improves endothelial dysfunction in human obesity. Diabetes Care 26:1673–1678
Seidell JC, Han TS, Feskens EJ, Lean ME (1997) Narrow hips and broad waist circumferences independently contribute to increased risk of non-insulin-dependent diabetes mellitus. J Intern Med 242:401–406
Seidell JC, Perusse L, Despres JP, Bouchard C (2001) Waist and hip circumferences have independent and opposite effects on cardiovascular disease risk factors: the Quebec Family Study. Am J Clin Nutr 74:315–321
SenBanerjee S, Lin Z, Atkins GB, Greif DM, Rao RM, Kumar A, Feinberg MW, Chen Z, Simon DI, Luscinskas FW, Michel TM, Gimbrone MA Jr, Garcia-Cardena G, Jain MK (2004) KLF2 is a novel transcriptional regulator of endothelial proinflammatory activation. J Exp Med 199:1305–1315
Serne EH, Stehouwer CD, Maaten JC ter, Wee PM ter, Rauwerda JA, Donker AJ, Gans RO (1999) Microvascular function relates to insulin sensitivity and blood pressure in normal subjects. Circulation 99:896–902
Serne EH, Jongh RT de, Eringa EC, IJzerman RG, Boer MP de, Stehouwer CD (2006) Microvascular dysfunction: causative role in the association between hypertension, insulin resistance and the metabolic syndrome? Essays Biochem 42:163–176
Sesti G, Federici IM, Hribal ML, Lauro D, Sbraccia P, Lauro R (2001) Defects of the insulin receptor substrate (IRS) system in human metabolic disorders. FASEB J 15:2099–2111
Shankar RR, Wu Y, Shen HQ, Zhu JS, Baron AD (2000) Mice with gene disruption of both endothelial and neuronal nitric oxide synthase exhibit insulin resistance. Diabetes 49:684–687
Shaul PW (1999) Regulation of vasodilator synthesis during lung development. Early Hum Dev 54:271–294
Shimokawa H, Yasutake H, Fujii K, Owada MK, Nakaike R, Fukumoto Y, Takayanagi T, Nagao T, Egashira K, Fujishima M, Takeshita A (1996) The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation. J Cardiovasc Pharmacol 28:703–711
Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T, Yamashita S, Miura M, Fukuda Y, Takemura K, Tokunaga K, Matsuzawa Y (1996) Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity. Nat Med 2:800–803
Shin HK, Kim YK, Kim KY, Lee JH, Hong KW (2004) Remnant lipoprotein particles induce apoptosis in endothelial cells by NAD(P)H oxidase-mediated production of superoxide and cytokines via lectin-like oxidized low-density lipoprotein receptor-1 activation: prevention by cilostazol. Circulation 109:1022–1028
Shinohara M, Thornalley PJ, Giardino I, Beisswenger P, Thorpe SR, Onorato J, Brownlee M (1998) Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis. J Clin Invest 101:1142–1147
Sierra-Honigmann MR, Nath AK, Murakami C, García-Cardeña G, Papapetropoulos A, Sessa WC, Madge LA, Schechner JS, Schwabb MB, Polverini PJ, Flores-Riveros JR (1998) Biological action of leptin as an angiogenic factor. Science 281:1683–1686
Simionescu M (2007) Implications of early structural-functional changes in the endothelium for vascular disease. Arterioscler Thromb Vasc Biol 27:266–274
Simionescu M, Gafencu A, Antohe F (2002) Transcytosis of plasma macromolecules in endothelial cells: a cell biological survey. Microsc Res Tech 57:269–288
Sjostrand M, Gudbjornsdottir S, Holmang A, Lonn L, Strindberg L, Lonnroth P (2002) Delayed transcapillary transport of insulin to muscle interstitial fluid in obese subjects. Diabetes 51:2742–2748
Soltis EE, Cassis LA (1991) Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. Clin Exp Hypertens [A] 13:277–296
Stehouwer CD, Smulders YM (2006) Microalbuminuria and risk for cardiovascular disease: analysis of potential mechanisms. J Am Soc Nephrol 17:2106–2111
Stehouwer CD, Stroes ES, Hackeng WH, Mulder PG, Den Ottolander GJ (1991) von Willebrand factor and development of diabetic nephropathy in IDDM. Diabetes 40:971–976
Stehouwer CD, Lambert J, Donker AJ, Hinsbergh VW van (1997) Endothelial dysfunction and pathogenesis of diabetic angiopathy. Cardiovasc Res 34:55–68
Stehouwer CD, Gall MA, Twisk JW, Knudsen E, Emeis JJ, Parving HH (2002) Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. Diabetes 51:1157–1165
Stehouwer CD, Henry RM, Dekker JM, Nijpels G, Heine RJ, Bouter LM (2004) Microalbuminuria is associated with impaired brachial artery, flow-mediated vasodilation in elderly individuals without and with diabetes: further evidence for a link between microalbuminuria and endothelial dysfunction–the Hoorn study. Kidney Int Suppl:S42-S44
Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321:405–412
Tamarat R, Silvestre JS, Huijberts M, Benessiano J, Ebrahimian TG, Duriez M, Wautier MP, Wautier JL, Levy BI (2003) Blockade of advanced glycation end-product formation restores ischemia-induced angiogenesis in diabetic mice. Proc Natl Acad Sci USA 100:8555–8560
Taniguchi CM, Emanuelli B, Kahn CR (2006) Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol 7:85–96
Tesfamariam B, DeFelice AF (2007) Endothelial injury in the initiation and progression of vascular disorders. Vascul Pharmacol 46:229–237
The Action to Control Cardiovascular Risk in Diabetes Study Group (2008) Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559
The ADVANCE Collaborative Group (2008) Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358:2560–2572
The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986
Thornalley PJ (1990) The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life. Biochem J 269:1–11
Tonelli J, Li W, Kishore P, Pajvani UB, Kwon E, Weaver C, Scherer PE, Hawkins M (2004) Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes. Diabetes 53:1621–1629
Trayhurn P, Wood IS (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92:347–355
Tsuda K, Nishio I (2004) Leptin and nitric oxide production in normotensive and hypertensive men. Obes Res 12:1223–1237
United Kingdom Prospective Diabetes Study (UKPDS) (1995) 13: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. BMJ 310:83–88
Vecchione C, Aretini A, Maffei A, Marino G, Selvetella G, Poulet R, Trimarco V, Frati G, Lembo G (2003) Cooperation between insulin and leptin in the modulation of vascular tone. Hypertension 42:166–170
Verlohren S, Dubrovska G, Tsang SY, Essin K, Luft FC, Huang Y, Gollasch M (2004) Visceral periadventitial adipose tissue regulates arterial tone of mesenteric arteries. Hypertension 44:271–276
Vicent D, Ilany J, Kondo T, Naruse K, Fisher SJ, Kisanuki YY, Bursell S, Yanagisawa M, King GL, Kahn CR (2003) The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance. J Clin Invest 111:1373–1380
Vincent MA, Barrett EJ, Lindner JR, Clark MG, Rattigan S (2003) Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin. Am J Physiol Endocrinol Metab 285:E123–E129
Vora DK, Fang ZT, Liva SM, Tyner TR, Parhami F, Watson AD, Drake TA, Territo MC, Berliner JA (1997) Induction of P-selectin by oxidized lipoproteins. Separate effects on synthesis and surface expression. Circ Res 80:810–818
Vosseller K, Wells L, Lane MD, Hart GW (2002) Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes. Proc Natl Acad Sci 99:5313–5318
Wautier MP, Chappey O, Corda S, Stern DM, Schmidt AM, Wautier JL (2001) Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol Endocrinol Metab 280:E685–E694
Weir MR (2007) Microalbuminuria and cardiovascular disease. Clin J Am Soc Nephrol 2:581–590
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808
Wellen KE, Hotamisligil GS (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 112:1785–1788
Wever RM, Dam T van, Rijn HJ van, Groot F de, Rabelink TJ (1997) Tetrahydrobiopterin regulates superoxide and nitric oxide generation by recombinant endothelial nitric oxide synthase. Biochem Biophys Res Commun 237:340–344
Wiernsperger N (1994) Vascular defects in the aetiology of peripheral insulin resistance in diabetes. A critical review of hypotheses and facts. Diabetes Metab Rev 10:287–307
Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053
Williams B, Baker AQ, Gallacher B, Lodwick D (1995) Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells. Hypertension 25:913–917
Williams IL, Wheatcroft SB, Shah AM, Kearney MT (2002) Obesity, atherosclerosis and the vascular endothelium: mechanisms of reduced nitric oxide bioavailability in obese humans. Int J Obes Relat Metab Disord 26:754–764
Williams IL, Chowienczyk PJ, Wheatcroft SB, Patel AG, Sherwood RA, Momin A, Shah AM, Kearney MT (2005) Endothelial function and weight loss in obese humans. Obes Surg 15:1055–1060
Williamson JR, Chang K, Frangos M, Hasan KS, Ido Y, Kawamura T, Nyengaard JR, van den EM, Kilo C, Tilton RG (1993) Hyperglycemic pseudohypoxia and diabetic complications. Diabetes 42:801–813
Winters B, Mo Z, Brooks-Asplund E, Kim S, Shoukas A, Li D, Nyhan D, Berkowitz DE (2000) Reduction of obesity, as induced by leptin, reverses endothelial dysfunction in obese (Lepob) mice. J Appl Physiol 89:2382–2390
Wolf G, Chen S, Ziyadeh FN (2005) From the periphery of the glomerular capillary wall toward the center of disease: podocyte injury comes of age in diabetic nephropathy. Diabetes 54:1626–1634
Wolinsky H (1980) A proposal linking clearance of circulating lipoproteins to tissue metabolic activity as a basis for understanding atherogenesis. Circ Res 47:301–311
Woo KS, Chook P, Yu CW, Sung RYT, Qiao M, Leung SSF, Lam CWK, Metreweli C, Celermajer DS (2004) Effects of diet and exercise on obesity-related vascular dysfunction in children. Circulation 109:1981–1986
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830
Xue X, Piao JH, Nakajima A, Sakon-Komazawa S, Kojima Y, Mori K, Yagita H, Okumura K, Harding H, Nakano H (2005) Tumor necrosis factor alpha [TNF(alpha)] induces the unfolded protein response (UPR) in a reactive oxygen species (ROS)-dependent fashion, and the UPR counteracts ROS accumulation by TNF(alpha). J Biol Chem 280:33917–33925
Yan SD, Schmidt AM, Anderson GM, Zhang J, Brett J, Zou YS, Pinsky D, Stern D (1994) Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem 269:9889–9897
Yan SF, Ramasamy R, Schmidt AM (2008) Mechanisms of disease: advanced glycation end-products and their receptor in inflammation and diabetes complications. Nat Clin Pract Endocrinol Metab 4:285–293
Yang YJ, Hope ID, Ader M, Bergman RN (1994) Importance of transcapillary insulin transport to dynamics of insulin action after intravenous glucose. Am J Physiol 266:E17–E25
Yao D, Taguchi T, Matsumura T, Pestell R, Edelstein D, Giardino I, Suske G, Rabbani N, Thornalley PJ, Sarthy VP, Hammes HP, Brownlee M (2007) High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A. J Biol Chem 282:31038–31045
Yasuda S, Miyazaki S, Kanda M, Goto Y, Suzuki M, Harano Y, Nonogi H (2006) Intensive treatment of risk factors in patients with type-2 diabetes mellitus is associated with improvement of endothelial function coupled with a reduction in the levels of plasma asymmetric dimethylarginine and endogenous inhibitor of nitric oxide synthase. Eur Heart J 27:1159–1165
Youd JM, Rattigan S, Clark MG (2000) Acute impairment of insulin-mediated capillary recruitment and glucose uptake in rat skeletal muscle in vivo by TNF-alpha. Diabetes 49:1904–1909
Yuan SY, Breslin JW, Perrin R, Gaudreault N, Guo M, Kargozaran H, Wu MH (2007) Microvascular permeability in diabetes and insulin resistance. Microcirculation 14:363–373
Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW (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
Zeeuw D de, Parving HH, Henning RH (2006) Microalbuminuria as an early marker for cardiovascular disease. J Am Soc Nephrol 17:2100–2105
Zhang K, Kaufman RJ (2008) From endoplasmic-reticulum stress to the inflammatory response. Nature 454:455–462
Zhang L, Newman JMB, Richards SM, Rattigan S, Clark MG (2005) Microvascular flow routes in muscle controlled by vasoconstrictors. Microvasc Res 70:7–16