Skeletal Muscle Vascular Function: A Counterbalance of Insulin Action

Microcirculation

Volumn 22, Issue 5, 2015, Pages 327-347

  Mahmoud, Abeer M ^a   Brown, Michael D ^a   Phillips, Shane A ^a   Haus, Jacob M ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

Hyperinsulinemia; Insulin resistance; Skeletal muscle; Vascular dysfunction

Indexed keywords

CARDIOVASCULAR DISEASE; DISEASE ASSOCIATION; GLYCOCALYX; HOMEOSTASIS; HUMAN; HYPERINSULINEMIA; INSULIN RESISTANCE; MUSCLE BLOOD FLOW; MUSCLE BLOOD VESSEL; MUSCLE CAPILLARY; NONHUMAN; OBESITY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; TRANSCYTOSIS; VASCULAR ENDOTHELIUM; VASCULAR RESISTANCE; VASOCONSTRICTION; VASODILATATION; ANIMAL; HYPERINSULINISM; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; VASCULAR DISEASE; VASCULARIZATION;

INSULIN; NITRIC OXIDE;

ANIMALS; HUMANS; HYPERINSULINISM; INSULIN; INSULIN RESISTANCE; MUSCLE, SKELETAL; NITRIC OXIDE; VASCULAR DISEASES;

EID: 84937033494     PISSN: 10739688     EISSN: 15498719     Source Type: Journal    
DOI: 10.1111/micc.12205     Document Type: Review

References (222)

1. Abbink-Zandbergen EJ, Vervoort G, Tack CJ, Lutterman JA, Schaper NC, Smits P. The role of adenosine in insulin-induced vasodilation. J Cardiovasc Pharmacol 34: 374-380, 1999.
2. Abdul-Ghani MA, DeFronzo RA. Pathogenesis of insulin resistance in skeletal muscle. J Biomed Biotechnol 2010: 476279, 2010.
3. Abhijit S, Bhaskaran R, Narayanasamy A, Chakroborty A, Manickam N, Dixit M, Mohan V, Balasubramanyam M. Hyperinsulinemia-induced vascular smooth muscle cell (VSMC) migration and proliferation is mediated by converging mechanisms of mitochondrial dysfunction and oxidative stress. Mol Cell Biochem 373: 95-105, 2013.
4. Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J 357: 593-615, 2001.
5. AlZadjali MA, Godfrey V, Khan F, Choy A, Doney AS, Wong AK, Petrie JR, Struthers AD, Lang CC. Insulin resistance is highly prevalent and is associated with reduced exercise tolerance in nondiabetic patients with heart failure. J Am Coll Cardiol 53: 747-753, 2009.
6. Anderson EA, Hoffman RP, Balon TW, Sinkey CA, Mark AL. Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Investig 87: 2246-2252, 1991.
7. Aoki K, Kato H, Terauchi Y. Divided-dose administration of miglitol just before and 15 minutes after the start of a meal smoothes postprandial plasma glucose excursions and serum insulin responses in healthy men. Endocr J 54: 1009-1014, 2007.
8. Arcaro G, Cretti A, Balzano S, Lechi A, Muggeo M, Bonora E, Bonadonna RC. Insulin causes endothelial dysfunction in humans: sites and mechanisms. Circulation 105: 576-582, 2002.
9. Armstrong SM, Khajoee V, Wang C, Wang T, Tigdi J, Yin J, Kuebler WM, Gillrie M, Davis SP, Ho M, Lee WL. Co-regulation of transcellular and paracellular leak across microvascular endothelium by dynamin and Rac. Am J Pathol 180: 1308-1323, 2012.
10. Azizi PM, Zyla RE, Guan S, Wang C, Liu J, Bolz SS, Heit B, Klip A, Lee WL. Clathrin-dependent entry and vesicle-mediated exocytosis define insulin transcytosis across microvascular endothelial cells. Mol Biol Cell 26: 740-750, 2015.
11. Babaei S, Picard P, Ravandi A, Monge JC, Lee TC, Cernacek P, Stewart DJ. Blockade of endothelin receptors markedly reduces atherosclerosis in LDL receptor deficient mice: role of endothelin in macrophage foam cell formation. Cardiovasc Res 48: 158-167, 2000.
12. Bailey SR, Mitra S, Flavahan S, Bergdall VK, Flavahan NA. In vivo endothelial denudation disrupts smooth muscle caveolae and differentially impairs agonist-induced constriction in small arteries. J Cardiovasc Pharmacol 49: 183-190, 2007.
13. Baron AD. Hemodynamic actions of insulin. Am J Physiol 267: E187-E202, 1994.
14. Baron AD, Brechtel-Hook G, Johnson A, Cronin J, Leaming R, Steinberg HO. Effect of perfusion rate on the time course of insulin-mediated skeletal muscle glucose uptake. Am J Physiol 271: E1067-E1072, 1996.
15. Baron AD, Brechtel-Hook G, Johnson A, Hardin D. Skeletal muscle blood flow. A possible link between insulin resistance and blood pressure. Hypertension 21: 129-135, 1993.
16. Baron AD, Steinberg HO, 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 Investig 96: 786-792, 1995.
17. Baron AD, Tarshoby M, Hook G, Lazaridis EN, Cronin J, Johnson A, Steinberg HO. Interaction between insulin sensitivity and muscle perfusion on glucose uptake in human skeletal muscle: evidence for capillary recruitment. Diabetes 49: 768-774, 2000.
18. Barrett EJ, Eggleston EM, Inyard AC, Wang H, Li G, Chai W, Liu Z. The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action. Diabetologia 52: 752-764, 2009.
19. Barrett EJ, Liu Z. The endothelial cell: an "early responder" in the development of insulin resistance. Rev Endocr Metab Disord 14: 21-27, 2013.
20. Barrett EJ, Rattigan S. Muscle perfusion: its measurement and role in metabolic regulation. Diabetes 61: 2661-2668, 2012.
21. Barrett EJ, Wang H, Upchurch CT, Liu Z. Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature. Am J Physiol Endocrinol Metab 301: E252-E263, 2011.
22. Bazil MK, Lappe RW, Webb RL. Pharmacologic characterization of an endothelinA (ETA) receptor antagonist in conscious rats. J Cardiovasc Pharmacol 20: 940-948, 1992.
23. Bendayan M, Rasio EA. Transport of insulin and albumin by the microvascular endothelium of the rete mirabile. J Cell Sci 109(Pt 7): 1857-1864, 1996.
24. Bergman RN, Finegood DT, Ader M. Assessment of insulin sensitivity in vivo. Endocr Rev 6: 45-86, 1985.
25. Berne C, Fagius J, Pollare T, Hjemdahl P. The sympathetic response to euglycaemic hyperinsulinaemia. Evidence from microelectrode nerve recordings in healthy subjects. Diabetologia 35: 873-879, 1992.
26. Berrazueta JR, Bhagat K, Vallance P, MacAllister RJ. Dose- and time-dependency of the dilator effects of the endothelin antagonist, BQ-123, in the human forearm. Br J Clin Pharmacol 44: 569-571, 1997.
27. Bijlstra P, van Ginneken EE, Huls M, van Dijk R, Smits P, Rongen GA. Glyburide inhibits dipyridamole-induced forearm vasodilation but not adenosine-induced forearm vasodilation. Clin Pharmacol Ther 75: 147-156, 2004.
28. Bonadonna RC, Saccomani MP, Del Prato S, Bonora E, DeFronzo RA, Cobelli C. Role of tissue-specific blood flow and tissue recruitment in insulin-mediated glucose uptake of human skeletal muscle. Circulation 98: 234-241, 1998.
29. Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Meigs JB, Bonadonna RC, Muggeo M. Insulin resistance as estimated by homeostasis model assessment predicts incident symptomatic cardiovascular disease in caucasian subjects from the general population: the Bruneck study. Diabetes Care 30: 318-324, 2007.
30. Bouallegue A, Daou GB, Srivastava AK. Endothelin-1-induced signaling pathways in vascular smooth muscle cells. Curr Vasc Pharmacol 5: 45-52, 2007.
31. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54: 1615-1625, 2005.
32. Brunner F, Doherty AM. Role of ET(B) receptors in local clearance of endothelin-1 in rat heart: studies with the antagonists PD 155080 and BQ-788. FEBS Lett 396: 238-242, 1996.
33. Cardoso CG Jr, Sakai D, Pinto LG, Labes E, de Gusmao JL, Abrahao SB, Tinucci T, Mion D Jr, da Fonseca AM, Forjaz CL. Neurovascular and hemodynamic responses to hyperinsulinemia in healthy postmenopausal women. Maturitas 58: 50-58, 2007.
34. Chai W, Liu J, Jahn LA, Fowler DE, Barrett EJ, Liu Z. Salsalate attenuates free fatty acid-induced microvascular and metabolic insulin resistance in humans. Diabetes Care 34: 1634-1638, 2011.
35. Chen YL, Messina EJ. Dilation of isolated skeletal muscle arterioles by insulin is endothelium dependent and nitric oxide mediated. Am J Physiol 270: H2120-H2124, 1996.
36. Chisaki K, Okuda Y, Suzuki S, Miyauchi T, Soma M, Ohkoshi N, Sone H, Yamada N, Nakajima T. Eicosapentaenoic acid suppresses basal and insulin-stimulated endothelin-1 production in human endothelial cells. Hypertens Res 26: 655-661, 2003.
37. Chiu JD, Richey JM, Harrison LN, Zuniga E, Kolka CM, Kirkman E, Ellmerer M, Bergman RN. Direct administration of insulin into skeletal muscle reveals that the transport of insulin across the capillary endothelium limits the time course of insulin to activate glucose disposal. Diabetes 57: 828-835, 2008.
38. Clark DE, Laeseke PF. Systeme International in the ICU in the United States. Chest 137: 932-937, 2010.
39. Cleland SJ, Petrie JR, Ueda S, Elliott HL, Connell JM. Insulin as a vascular hormone: implications for the pathophysiology of cardiovascular disease. Clin Exp Pharmacol Physiol 25: 175-184, 1998.
40. Clerk LH, Vincent MA, Jahn LA, Liu Z, Lindner JR, Barrett EJ. Obesity blunts insulin-mediated microvascular recruitment in human forearm muscle. Diabetes 55: 1436-1442, 2006.
41. Clerk LH, Vincent MA, Lindner JR, Clark MG, Rattigan S, Barrett EJ. The vasodilatory actions of insulin on resistance and terminal arterioles and their impact on muscle glucose uptake. Diabetes Metab Res Rev 20: 3-12, 2004.
42. Clozel M, Breu V, Burri K, Cassal JM, Fischli W, Gray GA, Hirth G, Loffler BM, Muller M, Neidhart W, Ramuz H. Pathophysiological role of endothelin revealed by the first orally active endothelin receptor antagonist. Nature 365: 759-761, 1993.
43. Coggins M, Lindner J, Rattigan S, Jahn L, Fasy E, Kaul S, Barrett E. Physiologic hyperinsulinemia enhances human skeletal muscle perfusion by capillary recruitment. Diabetes 50: 2682-2690, 2001.
44. Davenport AP. International Union of Pharmacology. XXIX. Update on endothelin receptor nomenclature. Pharmacol Rev 54: 219-226, 2002.
45. Davies MG, Hagen PO. Alterations in venous endothelial cell and smooth muscle cell relaxation induced by high glucose concentrations can be prevented by aminoguanidine. J Surg Res 63: 474-479, 1996.
46. de JR, Clark AD, IJzerman RG, Serne EH, de Vries G, Stehouwer CD. Physiological hyperinsulinaemia increases intramuscular microvascular reactive hyperaemia and vasomotion in healthy volunteers. Diabetologia 47: 978-986, 2004.
47. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14: 173-194, 1991.
48. DeFronzo RA, Ferrannini E, Hendler R, Felig P, Wahren J. Regulation of splanchnic and peripheral glucose uptake by insulin and hyperglycemia in man. Diabetes 32: 35-45, 1983.
49. DeFronzo RA, Gunnarsson R, Bjorkman O, Olsson M, Wahren J. Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus. J Clin Investig 76: 149-155, 1985.
50. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237: E214-E223, 1979.
51. Ding Y, Vaziri ND, Coulson R, Kamanna VS, Roh DD. Effects of simulated hyperglycemia, insulin, and glucagon on endothelial nitric oxide synthase expression. Am J Physiol Endocrinol Metab 279: E11-E17, 2000.
52. Disalvo RJ, Bloom WL, Brust AA, Ferguson RW, Ferris EB. A comparison of the metabolic and circulatory effects of epinephrine, nor-epinephrine and insulin hypoglycemia with observations on the influence of autonomic blocking agents. J Clin Investig 35: 568-577, 1956.
53. Du Bois D, Du Bois E. A formula to estimate the approximate surface area if height and weight be known. Nutrition 5: 303-311, 1916/1989; discussion 312-313.
54. d'Uscio LV, Barton M, Shaw S, Luscher TF. Chronic ET(A) receptor blockade prevents endothelial dysfunction of small arteries in apolipoprotein E-deficient mice. Cardiovasc Res 53: 487-495, 2002.
55. Dye AS, Huang H, Bauer JA, Hoffman RP. Hyperglycemia increases muscle blood flow and alters endothelial function in adolescents with type 1 diabetes. Exp Diabetes Res 2012: 170380, 2012.
56. Ebeling P, Koistinen HA, Koivisto VA. Insulin-independent glucose transport regulates insulin sensitivity. FEBS Lett 436: 301-303, 1998.
57. Egan BM, Stepniakowski K. Compensatory hyperinsulinemia and the forearm vasodilator response during an oral glucose-tolerance test in obese hypertensives. J Hypertens 12: 1061-1067, 1994.
58. Eggleston EM, Jahn LA, Barrett EJ. Hyperinsulinemia rapidly increases human muscle microvascular perfusion but fails to increase muscle insulin clearance: evidence that a saturable process mediates muscle insulin uptake. Diabetes 56: 2958-2963, 2007.
59. Eid HM, Reims H, Arnesen H, Kjeldsen SE, Lyberg T, Seljeflot I. Decreased levels of asymmetric dimethylarginine during acute hyperinsulinemia. Metabolism 56: 464-469, 2007.
60. Elshourbagy NA, Korman DR, Wu HL, Sylvester DR, Lee JA, Nuthalaganti P, Bergsma DJ, Kumar CS, Nambi P. Molecular characterization and regulation of the human endothelin receptors. J Biol Chem 268: 3873-3879, 1993.
61. Eringa EC, Stehouwer CD, van NAG, Ouwehand L, Westerhof N, Sipkema P. Vasoconstrictor effects of insulin in skeletal muscle arterioles are mediated by ERK1/2 activation in endothelium. Am J Physiol Heart Circ Physiol 287: H2043-H2048, 2004.
62. Eskens BJ, Mooij HL, Cleutjens JP, Roos JM, Cobelens JE, Vink H, Vanteeffelen JW. Rapid insulin-mediated increase in microvascular glycocalyx accessibility in skeletal muscle may contribute to insulin-mediated glucose disposal in rats. PLoS ONE 8: e55399, 2013.
63. Ferri C, Bellini C, Desideri G, Baldoncini R, Properzi G, Santucci A, De Mattia G. Circulating endothelin-1 levels in obese patients with the metabolic syndrome. Exp Clin Endocrinol Diabetes 105(Suppl. 2): 38-40, 1997.
64. 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 44: 431-436, 1995.
65. Ferri C, Pittoni V, Piccoli A, Laurenti O, Cassone MR, Bellini C, Properzi G, Valesini G, De Mattia G, Santucci A. Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo. J Clin Endocrinol Metab 80: 829-835, 1995.
66. Ferro CJ, Haynes WG, Hand MF, Webb DJ. Forearm vasoconstriction to endothelin-1 is impaired, but constriction to sarafotoxin 6c and vasodilatation to BQ-123 unaltered, in patients with essential hypertension. Clin Sci 103(Suppl. 48): 53S-58S, 2002.
67. Finsnes F, Lyberg T, Christensen G, Skjonsberg OH. Effect of endothelin antagonism on the production of cytokines in eosinophilic airway inflammation. Am J Physiol Lung Cell Mol Physiol 280: L659-L665, 2001.
68. Forstermann U. Nitric oxide and oxidative stress in vascular disease. Pflugers Archiv 459: 923-939, 2010.
69. Fujita S, Rasmussen BB, Cadenas JG, Grady JJ, Volpi E. Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability. Am J Physiol Endocrinol Metab 291: E745-E754, 2006.
70. Fukami K. Structure, regulation, and function of phospholipase C isozymes. J Biochem 131: 293-299, 2002.
71. Giugliano D, Marfella R, Coppola L, Verrazzo G, Acampora R, Giunta R, Nappo F, Lucarelli C, D'Onofrio F. Vascular effects of acute hyperglycemia in humans are reversed by l-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia. Circulation 95: 1783-1790, 1997.
72. Goodwill AG, Frisbee JC. Oxidant stress and skeletal muscle microvasculopathy in the metabolic syndrome. Vascul Pharmacol 57: 150-159, 2012.
73. Groen BB, Hamer HM, Snijders T, van Kranenburg J, Frijns D, Vink H, van Loon LJ. Skeletal muscle capillary density and microvascular function are compromised with aging and type 2 diabetes. J Appl Physiol 116: 998-1005, 2014.
74. Gudbjornsdottir S, Sjostrand M, Strindberg L, Lonnroth P. Decreased muscle capillary permeability surface area in type 2 diabetic subjects. J Clin Endocrinol Metab 90: 1078-1082, 2005.
75. Hamilton-Wessler M, Ader M, Dea MK, Moore D, Loftager M, Markussen J, Bergman RN. Mode of transcapillary transport of insulin and insulin analog NN304 in dog hindlimb: evidence for passive diffusion. Diabetes 51: 574-582, 2002.
76. Hanley AJ, Williams K, Stern MP, Haffner SM. Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study. Diabetes Care 25: 1177-1184, 2002.
77. Haynes WG, Ferro CJ, O'Kane KP, Somerville D, Lomax CC, Webb DJ. Systemic endothelin receptor blockade decreases peripheral vascular resistance and blood pressure in humans. Circulation 93: 1860-1870, 1996.
78. Haynes WG, Webb DJ. Contribution of endogenous generation of endothelin-1 to basal vascular tone. Lancet 344: 852-854, 1994.
79. Heberlein KR, Straub AC, Isakson BE. The myoendothelial junction: breaking through the matrix? Microcirculation 16: 307-322, 2009.
80. Hedman A, Andersson PE, Reneland R, Lithell HO. Insulin-mediated changes in leg blood flow are coupled to capillary density in skeletal muscle in healthy 70-year-old men. Metabolism 50: 1078-1082, 2001.
81. Herkner H, Klein N, Joukhadar C, Lackner E, Langenberger H, Frossard M, Bieglmayer C, Wagner O, Roden M, Muller M. Transcapillary insulin transfer in human skeletal muscle. Eur J Clin Invest 33: 141-146, 2003.
82. Hoffman RP, Sinkey CA, Dopp JM, Phillips BG. Lack of effect of alpha- and beta-adrenergic inhibition on forearm glucose uptake despite differences in forearm blood flow in healthy humans. Metabolism 51: 1506-1513, 2002.
83. Honig CR, Odoroff CL, Frierson JL. Capillary recruitment in exercise: rate, extent, uniformity, and relation to blood flow. Am J Physiol 238: H31-H42, 1980.
84. Irving RJ, Noon JP, Watt GC, Webb DJ, Walker BR. Activation of the endothelin system in insulin resistance. QJM 94: 321-326, 2001.
85. Ishibashi KI, Imamura T, Sharma PM, Huang J, Ugi S, Olefsky JM. Chronic endothelin-1 treatment leads to heterologous desensitization of insulin signaling in 3T3-L1 adipocytes. J Clin Investig 107: 1193-1202, 2001.
86. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24: 683-689, 2001.
87. Kang BY, Kleinhenz JM, Murphy TC, Hart CM. The PPARgamma ligand rosiglitazone attenuates hypoxia-induced endothelin signaling in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol 301: L881-L891, 2011.
88. Kashiwagi A, Shinozaki K, Nishio Y, Maegawa H, Maeno Y, Kanazawa A, Kojima H, Haneda M, Hidaka H, Yasuda H, Kikkawa R. Endothelium-specific activation of NAD(P)H oxidase in aortas of exogenously hyperinsulinemic rats. Am J Physiol 277: E976-E983, 1999.
89. Kashyap SR, Roman LJ, Lamont J, Masters BS, Bajaj M, Suraamornkul S, Belfort R, Berria R, Kellogg DL Jr, Liu Y, DeFronzo RA. Insulin resistance is associated with impaired nitric oxide synthase activity in skeletal muscle of type 2 diabetic subjects. J Clin Endocrinol Metab 90: 1100-1105, 2005.
90. Kashyap SR, Roman LJ, Mandarino L, DeFronzo R, Bajaj M. Hypoadiponectinemia is closely associated with impaired nitric oxide synthase activity in skeletal muscle of type 2 diabetic subjects. Metab Syndr Relat Disord 8: 459-463, 2010.
91. Kedzierski RM, Yanagisawa M. Endothelin system: the double-edged sword in health and disease. Annu Rev Pharmacol Toxicol 41: 851-876, 2001.
92. Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 113: 1888-1904, 2006.
93. King GL, Johnson SM. Receptor-mediated transport of insulin across endothelial cells. Science 227: 1583-1586, 1985.
94. Krssak M, Brehm A, Bernroider E, Anderwald C, Nowotny P, Dalla Man C, Cobelli C, Cline GW, Shulman GI, Waldhausl W, Roden M. Alterations in postprandial hepatic glycogen metabolism in type 2 diabetes. Diabetes 53: 3048-3056, 2004.
95. Kubota T, Kubota N, Kumagai H, Yamaguchi S, Kozono H, Takahashi T, Inoue M, Itoh S, Takamoto I, Sasako T, Kumagai K, Kawai T, Hashimoto S, Kobayashi T, Sato M, Tokuyama K, Nishimura S, Tsunoda M, Ide T, Murakami K, Yamazaki T, Ezaki O, Kawamura K, Masuda H, Moroi M, Sugi K, Oike Y, Shimokawa H, Yanagihara N, Tsutsui M, Terauchi Y, Tobe K, Nagai R, Kamata K, Inoue K, Kodama T, Ueki K, Kadowaki T. Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle. Cell Metab 13: 294-307, 2011.
96. Laakso M, Edelman SV, Brechtel G, Baron AD. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. J Clin Investig 85: 1844-1852, 1990.
97. Laakso M, Edelman SV, Brechtel G, Baron AD. Impaired insulin-mediated skeletal muscle blood flow in patients with NIDDM. Diabetes 41: 1076-1083, 1992.
98. Laine H, Yki-Jarvinen H, Kirvela O, Tolvanen T, Raitakari M, Solin O, Haaparanta M, Knuuti J, Nuutila P. Insulin resistance of glucose uptake in skeletal muscle cannot be ameliorated by enhancing endothelium-dependent blood flow in obesity. J Clin Investig 101: 1156-1162, 1998.
99. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288: 2709-2716, 2002.
100. Lee JH, Ragolia L. AKT phosphorylation is essential for insulin-induced relaxation of rat vascular smooth muscle cells. Am J Physiol Cell Physiol 291: C1355-C1365, 2006.
101. 2+ by cAMP in vascular smooth muscle cells. Am J Physiol 258: C399-C407, 1990.
102. Liu J, Jahn LA, Fowler DE, Barrett EJ, Cao W, Liu Z. Free fatty acids induce insulin resistance in both cardiac and skeletal muscle microvasculature in humans. J Clin Endocrinol Metab 96: 438-446, 2011.
103. Loffler BM, Breu V, Clozel M. Effect of different endothelin receptor antagonists and of the novel non-peptide antagonist Ro 46-2005 on endothelin levels in rat plasma. FEBS Lett 333: 108-110, 1993.
104. Lott ME, Hogeman C, Herr M, Gabbay R, Sinoway LI. Effects of an oral glucose tolerance test on the myogenic response in healthy individuals. Am J Physiol Heart Circ Physiol 292: H304-H310, 2007.
105. Lteif A, Vaishnava P, Baron AD, Mather KJ. Endothelin limits insulin action in obese/insulin-resistant humans. Diabetes 56: 728-734, 2007.
106. Luscher TF, Barton M. Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation 102: 2434-2440, 2000.
107. Lusis AJ. Atherosclerosis. Nature 407: 233-241, 2000.
108. Mah E, Noh SK, Ballard KD, Matos ME, Volek JS, Bruno RS. Postprandial hyperglycemia impairs vascular endothelial function in healthy men by inducing lipid peroxidation and increasing asymmetric dimethylarginine:arginine. J Nutr 141: 1961-1968, 2011.
109. Mather K, Anderson TJ, Verma S. Insulin action in the vasculature: physiology and pathophysiology. J Vasc Res 38: 415-422, 2001.
110. Mather KJ, Lteif A, Steinberg HO, Baron AD. Interactions between endothelin and nitric oxide in the regulation of vascular tone in obesity and diabetes. Diabetes 53: 2060-2066, 2004.
111. Mather KJ, Mirzamohammadi B, Lteif A, Steinberg HO, Baron AD. Endothelin contributes to basal vascular tone and endothelial dysfunction in human obesity and type 2 diabetes. Diabetes 51: 3517-3523, 2002.
112. Mazzuca MQ, Khalil RA. Vascular endothelin receptor type B: structure, function and dysregulation in vascular disease. Biochem Pharmacol 84: 147-162, 2012.
113. 2+ antagonist-insensitive coronary smooth muscle contraction via activation of epsilon-protein kinase C. Hypertension 43: 897-904, 2004.
114. Meijer RI, De Boer MP, Groen MR, Eringa EC, Rattigan S, Barrett EJ, Smulders YM, Serne EH. Insulin-induced microvascular recruitment in skin and muscle are related and both are associated with whole-body glucose uptake. Microcirculation 19: 494-500, 2012.
115. Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol 61: 391-415, 1999.
116. Molero L, Farre J, Garcia-Mendez A, Jimenez Mateos-Caceres P, Carrasco Martin C, Millas I, Navarro F, Cordoba M, Casado S, Lopez-Farre A. Endothelin-1 induced proinflammatory markers in the myocardium and leukocytes of guinea-pigs: role of glycoprotein IIB/IIIA receptors. Cardiovas Res 57: 109-118, 2003.
117. 2+ but requires phosphorylation by Akt at Ser(1179). J Biol Chem 276: 30392-30398, 2001.
118. Montagnani M, Golovchenko I, Kim I, Koh GY, Goalstone ML, Mundhekar AN, Johansen M, Kucik DF, Quon MJ, Draznin B. Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells. J Biol Chem 277: 1794-1799, 2002.
119. Montagnani M, Ravichandran LV, Chen H, Esposito DL, Quon MJ. 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, 2002.
120. Morgantini C, Stea F, Boldrini B, Duranti E, Ghiadoni L, Natali A. Effect of mild hyperisulinemia on conduit vessel endothelial function: role of noradrenergic activation. J Hypertens 30: 720-724, 2012.
121. Mulder AH, van Dijk AP, Smits P, Tack CJ. Real-time contrast imaging: a new method to monitor capillary recruitment in human forearm skeletal muscle. Microcirculation 15: 203-213, 2008.
122. Muniyappa R, Karne RJ, Hall G, Crandon SK, Bronstein JA, Ver MR, Hortin GL, Quon MJ. Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects. Diabetes 55: 3142-3150, 2006.
123. Muniyappa R, Montagnani M, Koh KK, Quon MJ. Cardiovascular actions of insulin. Endocr Rev 28: 463-491, 2007.
124. Murphy RA, Walker JS. Inhibitory mechanisms for cross-bridge cycling: the nitric oxide-cGMP signal transduction pathway in smooth muscle relaxation. Acta Physiol Scand 164: 373-380, 1998.
125. Myung SC, Keum EM, Park SY, Lee MY, Kim SC. Vasomotor action of insulin on the rabbit normal cavernous smooth muscle. Eur J Pharmacol 536: 142-147, 2006.
126. Natali A, Quinones Galvan A, Pecori N, Sanna G, Toschi E, Ferrannini E. Vasodilation with sodium nitroprusside does not improve insulin action in essential hypertension. Hypertension 31: 632-636, 1998.
127. Nava P, Collados MT, Masso F, Guarner V. Endothelin mediation of insulin and glucose-induced changes in vascular contractility. Hypertension 30: 825-829, 1997.
128. Newman JM, Ross RM, Richards SM, Clark MG, Rattigan S. Insulin and contraction increase nutritive blood flow in rat muscle in vivo determined by microdialysis of L-[14C]glucose. J Physiol 585: 217-229, 2007.
129. Nieuwdorp M, Meuwese MC, Vink H, Hoekstra JB, Kastelein JJ, Stroes ES. The endothelial glycocalyx: a potential barrier between health and vascular disease. Curr Opin Lipidol 16: 507-511, 2005.
130. Nishikibe M, Tsuchida S, Okada M, Fukuroda T, Shimamoto K, Yano M, Ishikawa K, Ikemoto F. Antihypertensive effect of a newly synthesized endothelin antagonist, BQ-123, in a genetic hypertensive model. Life Sci 52: 717-724, 1993.
131. Nitenberg A, Cosson E, Pham I. Postprandial endothelial dysfunction: role of glucose, lipids and insulin. Diabetes Metab 32: 2S28-2S33, 2006.
132. Nuutila P, Raitakari M, Laine H, Kirvela O, Takala T, Utriainen T, Makimattila S, Pitkanen OP, Ruotsalainen U, Iida H, Knuuti J, Yki-Jarvinen H. Role of blood flow in regulating insulin-stimulated glucose uptake in humans. Studies using bradykinin, [15O]water, and [18F]fluoro-deoxy-glucose and positron emission tomography. J Clin Investig 97: 1741-1747, 1996.
133. Nystrom T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahren B, Sjoholm A. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab 287: E1209-E1215, 2004.
134. Okubo K, Kushiro T, Takahashi A, Kanmatsuse K. Role of endothelium-derived hyperpolarizing factor in insulin-induced vasodilation in rat mesenteric artery. Nihon Jinzo Gakkai Shi 41: 685-691, 1999.
135. Olsen DB, Sacchetti M, Dela F, Ploug T, Saltin B. Glucose clearance is higher in arm than leg muscle in type 2 diabetes. J Physiol 565: 555-562, 2005.
136. Pashkow FJ. Oxidative stress and inflammation in heart disease: do antioxidants have a role in treatment and/or prevention? Int J Inflamm 2011: 514623, 2011.
137. Pate M, Damarla V, Chi DS, Negi S, Krishnaswamy G. Endothelial cell biology: role in the inflammatory response. Adv Clin Chem 52: 109-130, 2010.
138. Petersen KF, Dufour S, Savage DB, Bilz S, Solomon G, Yonemitsu S, Cline GW, Befroy D, Zemany L, Kahn BB, Papademetris X, Rothman DL, Shulman GI. The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proc Natl Acad Sci USA 104: 12587-12594, 2007.
139. Pierce KL, Premont RT, Lefkowitz RJ. Seven-transmembrane receptors. Nat Rev Mol Cell Biol 3: 639-650, 2002.
140. Potenza MA, Marasciulo FL, Chieppa DM, Brigiani GS, Formoso G, Quon MJ, Montagnani M. 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, 2005.
141. Potenza MA, Marasciulo FL, Tarquinio M, Quon MJ, Montagnani M. Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance. Diabetes 55: 3594-3603, 2006.
142. Qvisth V, Hagstrom-Toft E, Moberg E, Sjoberg S, Bolinder J. Lactate release from adipose tissue and skeletal muscle in vivo: defective insulin regulation in insulin-resistant obese women. Am J Physiol Endocrinol Metab 292: E709-E714, 2007.
143. Raitakari M, Knuuti MJ, Ruotsalainen U, Laine H, Makea P, Teras M, Sipila H, Niskanen T, Raitakari OT, Iida H, Härkönen R, Wegelius U, Yki-Järvinen H, Nuutila P. Insulin increases blood volume in human skeletal muscle: studies using [15O]CO and positron emission tomography. Am J Physiol 269: E1000-E1005, 1995.
144. 2O, [15O]CO, and positron emission tomography. Diabetes 46: 2017-2021, 1997.
145. Rask-Madsen C, King GL. Endothelium-dependent delivery of insulin to muscle interstitium. Cell Metab 13: 236-238, 2011.
146. Rask-Madsen C, Li Q, Freund B, Feather D, Abramov R, Wu IH, Chen K, Yamamoto-Hiraoka J, Goldenbogen J, Sotiropoulos KB, Clermont A, Geraldes P, Dall'Osso C, Wagers AJ, Huang PL, Rekhter M, Scalia R, Kahn CR, King GL. Loss of insulin signaling in vascular endothelial cells accelerates atherosclerosis in apolipoprotein E null mice. Cell Metab 11: 379-389, 2010.
147. Rattigan S, Clark MG, Barrett EJ. Hemodynamic actions of insulin in rat skeletal muscle: evidence for capillary recruitment. Diabetes 46: 1381-1388, 1997.
148. Rennings AJ, Smits P, Stewart MW, Tack CJ. Fluid retention and vascular effects of rosiglitazone in obese, insulin-resistant, nondiabetic subjects. Diabetes Care 29: 581-587, 2006.
149. Roden M. Clinical Diabetes Research: Methods and Techniques, 1st edn. Chichester, UK: John Wiley and Sons, 2007.
150. Rongen GA, Smits P, Ver Donck K, Willemsen JJ, De Abreu RA, Van Belle H, Thien T. Hemodynamic and neurohumoral effects of various grades of selective adenosine transport inhibition in humans. Implications for its future role in cardioprotection. J Clin Invest 95: 658-668, 1995.
151. Rosdahl H, Lind L, Millgard J, Lithell H, Ungerstedt U, Henriksson J. Effect of physiological hyperinsulinemia on blood flow and interstitial glucose concentration in human skeletal muscle and adipose tissue studied by microdialysis. Diabetes 47: 1296-1301, 1998.
152. Ross RM, Kolka CM, Rattigan S, Clark MG. Acute blockade by endothelin-1 of haemodynamic insulin action in rats. Diabetologia 50: 443-451, 2007.
153. Rowe JW, Young JB, Minaker KL, Stevens AL, Pallotta J, Landsberg L. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes 30: 219-225, 1981.
154. Roy D, Perreault M, Marette A. Insulin stimulation of glucose uptake in skeletal muscles and adipose tissues in vivo is NO dependent. Am J Physiol 274: E692-E699, 1998.
155. Sanchez-Margalet V, Goldfine ID, Vlahos CJ, Sung CK. Role of phosphatidylinositol-3-kinase in insulin receptor signaling: studies with inhibitor, LY294002. Biochem Biophys Res Commun 204: 446-452, 1994.
156. Sauder MA, Liu J, Jahn LA, Fowler DE, Chai W, Liu Z. Candesartan acutely recruits skeletal and cardiac muscle microvasculature in healthy humans. J Clin Endocrinol Metab 97: E1208-E1212, 2012.
157. Sausbier M, Schubert R, Voigt V, Hirneiss C, Pfeifer A, Korth M, Kleppisch T, Ruth P, Hofmann F. Mechanisms of NO/cGMP-dependent vasorelaxation. Circ Res 87: 825-830, 2000.
158. Scheede-Bergdahl C, Olsen DB, Reving D, Boushel R, Dela F. Insulin and non-insulin mediated vasodilation and glucose uptake in patients with type 2 diabetes. Diabetes Res Clin Pract 85: 243-251, 2009.
159. Scherrer U, Randin D, Vollenweider P, Vollenweider L, Nicod P. Nitric oxide release accounts for insulin's vascular effects in humans. J Clin Investig 94: 2511-2515, 1994.
160. Scherrer U, Sartori C. Insulin as a vascular and sympathoexcitatory hormone: implications for blood pressure regulation, insulin sensitivity, and cardiovascular morbidity. Circulation 96: 4104-4113, 1997.
161. Scherrer U, Vollenweider P, Randin D, Jequier E, Nicod P, Tappy L. Suppression of insulin-induced sympathetic activation and vasodilation by dexamethasone in humans. Circulation 88: 388-394, 1993.
162. Serne EH, de JR, Eringa EC, RG IJ, Stehouwer CD. Microvascular dysfunction: a potential pathophysiological role in the metabolic syndrome. Hypertension 50: 204-211, 2007.
163. Shaw SG, Boden PJ. Insulin resistance, obesity and the metabolic syndrome. Is there a therapeutic role for endothelin-1 antagonists? Curr Vasc Pharmacol 3: 359-363, 2005.
164. Shemyakin A, Bohm F, Wagner H, Efendic S, Bavenholm P, Pernow J. Enhanced endothelium-dependent vasodilatation by dual endothelin receptor blockade in individuals with insulin resistance. J Cardiovasc Pharmacol 47: 385-390, 2006.
165. Shemyakin A, Salehzadeh F, Bohm F, Al-Khalili L, Gonon A, Wagner H, Efendic S, Krook A, Pernow J. Regulation of glucose uptake by endothelin-1 in human skeletal muscle in vivo and in vitro. J Clin Endocrinol Metab 95: 2359-2366, 2010.
166. Shoemaker JK, Bonen A. Vascular actions of insulin in health and disease. Can J Appl Physiol 20: 127-154, 1995.
167. Singhal P, Caumo A, Carey PE, Cobelli C, Taylor R. Regulation of endogenous glucose production after a mixed meal in type 2 diabetes. Am J Physiol Endocrinol Metab 283: E275-E283, 2002.
168. Sjoberg KA, Rattigan S, Hiscock N, Richter EA, Kiens B. A new method to study changes in microvascular blood volume in muscle and adipose tissue: real-time imaging in humans and rat. Am J Physiol Heart Circ Physiol 301: H450-H458, 2011.
169. Sjostrand M, Gudbjornsdottir S, Holmang A, Lonn L, Strindberg L, Lonnroth P. Delayed transcapillary transport of insulin to muscle interstitial fluid in obese subjects. Diabetes 51: 2742-2748, 2002.
170. Solomon TP, Haus JM, Li Y, Kirwan JP. Progressive hyperglycemia across the glucose tolerance continuum in older obese adults is related to skeletal muscle capillarization and nitric oxide bioavailability. J Clin Endocrinol Metab 96: 1377-1384, 2011.
171. Sonne MP, Alibegovic AC, Hojbjerre L, Vaag A, Stallknecht B, Dela F. Effect of 10 days of bedrest on metabolic and vascular insulin action: a study in individuals at risk for type 2 diabetes. J Appl Physiol 108: 830-837, 2010.
172. Stankova J, D'Orleans-Juste P, Rola-Pleszczynski M. ET-1 induces IL-6 gene expression in human umbilical vein endothelial cells: synergistic effect of IL-1. Am J Physiol 271: C1073-C1078, 1996.
173. Steil GM, Ader M, Moore DM, Rebrin K, Bergman RN. Transendothelial insulin transport is not saturable in vivo. No evidence for a receptor-mediated process. J Clin Investig 97: 1497-1503, 1996.
174. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Investig 94: 1172-1179, 1994.
175. Steinberg HO, Paradisi G, Hook G, Crowder K, Cronin J, Baron AD. Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production. Diabetes 49: 1231-1238, 2000.
176. Straub AC, Butcher JT, Billaud M, Mutchler SM, Artamonov MV, Nguyen AT, Johnson T, Best AK, Miller MP, Palmer LA, Columbus L, Somlyo AV, Le TH, Isakson BE. Hemoglobin alpha/eNOS coupling at myoendothelial junctions is required for nitric oxide scavenging during vasoconstriction. Arterioscler Thromb Vasc Biol 34: 2594-2600, 2014.
177. Straub AC, Lohman AW, Billaud M, Johnstone SR, Dwyer ST, Lee MY, Bortz PS, Best AK, Columbus L, Gaston B, Isakson BE. Endothelial cell expression of haemoglobin alpha regulates nitric oxide signalling. Nature 491: 473-477, 2012.
178. Straub AC, Zeigler AC, Isakson BE. The myoendothelial junction: connections that deliver the message. Physiology 29: 242-249, 2014.
179. Strawbridge AB, Elmendorf JS. Phosphatidylinositol 4, 5-bisphosphate reverses endothelin-1-induced insulin resistance via an actin-dependent mechanism. Diabetes 54: 1698-1705, 2005.
180. Subaran SC, Sauder MA, Chai W, Jahn LA, Fowler DE, Aylor KW, Basu A, Liu Z. GLP-1 at physiological concentrations recruits skeletal and cardiac muscle microvasculature in healthy humans. Clin Sci 127: 163-170, 2014.
181. Sun XJ, Miralpeix M, Myers MG Jr, Glasheen EM, Backer JM, Kahn CR, White MF. Expression and function of IRS-1 in insulin signal transmission. J Biol Chem 267: 22662-22672, 1992.
182. Tack CJ, Heeremans M, Thien T, Lutterman JA, Smits P. Regional hyperinsulinemia induces vasodilation but does not modulate adrenergic responsiveness in humans. J Cardiovasc Pharmacol 28: 245-251, 1996.
183. Tack CJ, Lutterman JA, Vervoort G, Thien T, Smits P. Activation of the sodium-potassium pump contributes to insulin-induced vasodilation in humans. Hypertension 28: 426-432, 1996.
184. Tack CJ, Ong MK, Lutterman JA, Smits P. Insulin-induced vasodilatation and endothelial function in obesity/insulin resistance. Effects of troglitazone. Diabetologia 41: 569-576, 1998.
185. Takahashi K, Ghatei MA, Lam HC, O'Halloran DJ, Bloom SR. Elevated plasma endothelin in patients with diabetes mellitus. Diabetologia 33: 306-310, 1990.
186. Tarbell JM, Ebong EE. The endothelial glycocalyx: a mechano-sensor and -transducer. Sci Signal 1: pt 8, 2008.
187. Tesfamariam B, Brown ML, Deykin D, Cohen RA. Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta. J Clin Investig 85: 929-932, 1990.
188. Tesfamariam B, Cohen RA. Free radicals mediate endothelial cell dysfunction caused by elevated glucose. Am J Physiol 263: H321-H326, 1992.
189. Tessari P, Cecchet D, Cosma A, Vettore M, Coracina A, Millioni R, Iori E, Puricelli L, Avogaro A, Vedovato M. Nitric oxide synthesis is reduced in subjects with type 2 diabetes and nephropathy. Diabetes 59: 2152-2159, 2010.
190. Tessari P, Coracina A, Puricelli L, Vettore M, Cosma A, Millioni R, Cecchet D, Avogaro A, Tiengo A, Kiwanuka E. Acute effect of insulin on nitric oxide synthesis in humans: a precursor-product isotopic study. Am J Physiol Endocrinol Metab 293: E776-E782, 2007.
191. Timmerman KL, Lee JL, Fujita S, Dhanani S, Dreyer HC, Fry CS, Drummond MJ, Sheffield-Moore M, Rasmussen BB, Volpi E. Pharmacological vasodilation improves insulin-stimulated muscle protein anabolism but not glucose utilization in older adults. Diabetes 59: 2764-2771, 2010.
192. Trovati M, Anfossi G. Influence of insulin and of insulin resistance on platelet and vascular smooth muscle cell function. J Diabetes Complications 16: 35-40, 2002.
193. 3-excretion. Metabolism 46: 406-409, 1997.
194. Urschel KL, Escobar J, McCutcheon LJ, Geor RJ. Effects of the rate of insulin infusion during isoglycemic, hyperinsulinemic clamp procedures on measures of insulin action in healthy, mature thoroughbred mares. Domest Anim Endocrinol 47: 83-91, 2014.
195. Utriainen T, Malmstrom R, Makimattila S, Yki-Jarvinen H. Methodological aspects, dose-response characteristics and causes of interindividual variation in insulin stimulation of limb blood flow in normal subjects. Diabetologia 38: 555-564, 1995.
196. van Gurp PJ, Rongen GA, Lenders JW, Al Nabawy AK, Timmers HJ, Tack CJ. Sustained hyperglycaemia increases muscle blood flow but does not affect sympathetic activity in resting humans. Eur J Appl Physiol 93: 648-654, 2005.
197. van Veen S, Frolich M, Chang PC. Acute hyperglycaemia in the forearm induces vasodilation that is not modified by hyperinsulinaemia. J Hum Hypertens 13: 263-268, 1999.
198. Veniant M, Clozel JP, Hess P, Clozel M. Endothelin plays a role in the maintenance of blood pressure in normotensive guinea pigs. Life Sci 55: 445-454, 1994.
199. Verhaar MC, Strachan FE, Newby DE, Cruden NL, Koomans HA, Rabelink TJ, Webb DJ. Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade. Circulation 97: 752-756, 1998.
200. Vicent D, Ilany J, Kondo T, Naruse K, Fisher SJ, Kisanuki YY, Bursell S, Yanagisawa M, King GL, Kahn CR. The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance. J Clin Investig 111: 1373-1380, 2003.
201. Vincent MA, Barrett EJ, Lindner JR, Clark MG, Rattigan S. Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin. Am J Physiol Endocrinol Metab 285: E123-E129, 2003.
202. Vincent MA, Clerk LH, Lindner JR, Klibanov AL, Clark MG, Rattigan S, Barrett EJ. Microvascular recruitment is an early insulin effect that regulates skeletal muscle glucose uptake in vivo. Diabetes 53: 1418-1423, 2004.
203. Vincent MA, Clerk LH, Rattigan S, Clark MG, Barrett EJ. Active role for the vasculature in the delivery of insulin to skeletal muscle. Clin Exp Pharmacol Physiol 32: 302-307, 2005.
204. Vincent MA, Dawson D, Clark AD, Lindner JR, Rattigan S, Clark MG, Barrett EJ. Skeletal muscle microvascular recruitment by physiological hyperinsulinemia precedes increases in total blood flow. Diabetes 51: 42-48, 2002.
205. Virdis A, Neves MF, Duranti E, Bernini G, Taddei S. Microvascular endothelial dysfunction in obesity and hypertension. Curr Pharm Des 19: 2382-2389, 2013.
206. Vollenweider P, Randin D, Tappy L, Jequier E, Nicod P, Scherrer U. Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans. J Clin Investig 93: 2365-2371, 1994.
207. Vollenweider P, Tappy L, Randin D, Schneiter P, Jequier E, Nicod P, Scherrer U. Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans. J Clin Investig 92: 147-154, 1993.
208. Wang H, Liu Z, Li G, Barrett EJ. The vascular endothelial cell mediates insulin transport into skeletal muscle. Am J Physiol Endocrinol Metab 291: E323-E332, 2006.
209. Wang H, Wang AX, Liu Z, Barrett EJ. Insulin signaling stimulates insulin transport by bovine aortic endothelial cells. Diabetes 57: 540-547, 2008.
210. Wang Y, Zeng FH, Long CL, Pan ZY, Cui WY, Wang RH, Liu GS, Wang H. The novel ATP-sensitive potassium channel opener iptakalim prevents insulin resistance associated with hypertension via restoring endothelial function. Acta Pharmacol Sin 32: 1466-1474, 2011.
211. Wedgwood S, McMullan DM, Bekker JM, Fineman JR, Black SM. Role for endothelin-1-induced superoxide and peroxynitrite production in rebound pulmonary hypertension associated with inhaled nitric oxide therapy. Circ Res 89: 357-364, 2001.
212. Weil BR, Westby CM, Greiner JJ, Stauffer BL, DeSouza CA. Elevated endothelin-1 vasoconstrictor tone in prehypertensive adults. Can J Cardiol 28: 347-353, 2012.
213. Wiberg B, Sundstrom J, Zethelius B, Lind L. Insulin sensitivity measured by the euglycaemic insulin clamp and proinsulin levels as predictors of stroke in elderly men. Diabetologia 52: 90-96, 2009.
214. Wilson SH, Simari RD, Lerman A. The effect of endothelin-1 on nuclear factor kappa B in macrophages. Biochem Biophys Res Commun 286: 968-972, 2001.
215. Wimalasundera RC, Mc GTSA, Regan L, Hughes AD. Action of the endothelin receptor (ETA) antagonist BQ-123 on forearm blood flow in young normotensive subjects. Clin Sci 102: 661-666, 2002.
216. Xu L, Badr MZ. Enhanced potential for oxidative stress in hyperinsulinemic rats: imbalance between hepatic peroxisomal hydrogen peroxide production and decomposition due to hyperinsulinemia. Horm Metab Res 31: 278-282, 1999.
217. Yang YJ, Hope ID, Ader M, Bergman RN. Insulin transport across capillaries is rate limiting for insulin action in dogs. J Clin Investig 84: 1620-1628, 1989.
218. Young CN, Deo SH, Chaudhary K, Thyfault JP, Fadel PJ. Insulin enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in humans. J Physiol 588: 3593-3603, 2010.
219. Zavaroni I, Platti PM, Monti LD, Gasparini P, Barilli LA, Massironi P, Ardigo D, Valsecchi G, Delsignore R, Reaven GM. Plasma nitric oxide concentrations are elevated in insulin-resistant healthy subjects. Metabolism 49: 959-961, 2000.
220. Zeng G, Nystrom FH, Ravichandran LV, Cong LN, Kirby M, Mostowski H, Quon MJ. Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells. Circulation 101: 1539-1545, 2000.
221. Zeng G, Quon MJ. Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. J Clin Investig 98: 894-898, 1996.
222. Zethelius B, Lithell H, Hales CN, Berne C. Insulin sensitivity, proinsulin and insulin as predictors of coronary heart disease. A population-based 10-year, follow-up study in 70-year old men using the euglycaemic insulin clamp. Diabetologia 48: 862-867, 2005.