Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance
Open accessAbstract
To test the hypothesis that obesity/insulin resistance impairs both endothelium-dependent vasodilation and insulin-mediated augmentation of endothelium-dependent vasodilation, we studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of methacholine chloride (MCh) or sodium nitroprusside (SNP) during saline infusion and euglycemic hyperinsulinemia in lean insulin-sensitive controls (C), in obese insulin-resistant subjects (OB), and in subjects with non-insulin-dependent diabetes mellitus (NIDDM). MCh induced increments in LBF were approximately 40% and 55% lower in OB and NIDDM, respectively, as compared with C (P < 0.05). Euglycemic hyperinsulinemia augmented the LBF response to MCh by - 50% in C (P < 0.05 vs saline) but not in OB and NIDDM. SNP caused comparable increments in LBF in all groups. Regression analysis revealed a significant inverse correlation between the maximal LBF change in response to MCh and body fat content. Thus, obesity/insulin resistance is associated with (a) blunted endothelium-dependent, but normal endothelium-independent vasodilation and (b) failure of euglycemic hyperinsulinemia to augment endothelium-dependent vasodilation. Therefore, obese/insulin-resistant subjects are characterized by endothelial dysfunction and endothelial resistance to insulin's effect on enhancement of endothelium-dependent vasodilation. This endothelial dysfunction could contribute to the increased risk of atherosclerosis in obese insulin-resistant subjects.
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Insulin resistance per se has a direct impact on endothelial function, distinct from effects related to unfavorable changes in lipid composition or blood pressure.
“Furthermore, IR per se has a direct impact on endothelial function, distinct from effects related to unfavorable changes in lipid composition or blood pressure (9).”
From Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus (2001) · cites this paper as [9]
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Chagnac, A., Weinstein, T., Herman, M., Hirsh, J., Gafter, U., & Ori, Y. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000068462.38661.89 · Cited by 537 · see citing works
Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases
Cersósimo, E., & DeFronzo, R. A. (2006) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.634 · Cited by 525 · see citing works
Obesity and Obesity-Initiated Metabolic Syndrome
Wahba, I. M., & MAK, R. H. K. (2007) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.04071206 · Cited by 518 · see citing works
Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus
Mather, K. J., Verma, S., & Anderson, T. J. (2001) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(01)01129-9 · Cited by 513 · see citing works
A Review of the Microcirculation of Adipose Tissue: Anatomic, Metabolic, and Angiogenic Perspectives
Crandall, D. L., Hausman, G. J., & Kral, J. G. (1997) · Microcirculation · doi:10.3109/10739689709146786 · Cited by 508 · see citing works
Insulin Resistance and Cardiovascular Disease1
McFarlane, S. I., Banerji, M., & Sowers, J. R. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.2.7202 · Cited by 506 · see citing works
“Second, insulin stimulation of blood flow is blunted in these individuals (59, 60, 62).”
BackgroundMechanisms of Disease: endothelial dysfunction in insulin resistance and diabetes
Rask‐Madsen, C., & King, G. L. (2006) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0366 · Cited by 483 · see citing works
“diabetes as well as in obese, insulin resistant people”
BackgroundInsulin resistance and hypertension
Sowers, J. R. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00026.2004 · Cited by 475 · see citing works
“This normal response is lost in Ins-resistant/obese persons, suggesting resistance to the action of Ins to induce vascular NO production (69).”
Polycystic Ovary Syndrome Is Associated With Endothelial Dysfunction
Paradisi, G., Steinberg, H. O., Hempfling, A., Cronin, J., Brechtel, G., Shepard, M. K., & Baron, A. (2001) · Circulation · doi:10.1161/01.cir.103.10.1410 · Cited by 476 · see citing works
“Discussion The results of this study reveal the following new findings: (1) compared with age- and weight-matched control subjects, women with PCOS exhibit an'50% reduction in endothelium-dependent vasodilation; (2) the physiological ability of insulin to cause endothelium-dependent vasodilation is markedly impaired i…”
BackgroundResultErectile Dysfunction in Diabetes Mellitus
Malavige, L. S., & Lévy, J. (2009) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2008.01168.x · Cited by 444 · see citing works
Diabetes mellitus as a prothrombotic condition
Grant, P. J. (2007) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01824.x · Cited by 443 · see citing works
Balletshofer, B. M., Rittig, K., Enderle, M. D., Volk, A., Maerker, E., Jacob, S., Matthaei, S., Kristian, R. E. T. T., & Häring, H. U. (2000) · Circulation · doi:10.1161/01.cir.101.15.1780 · Cited by 437 · see citing works
Surdacki, A., Nowicki, M. P., Sandmann, J., Tsikas, D., Boeger, R. H., Bode-Boeger, S. M., Kruszelnicka-Kwiatkowska, O., Kokot, F., Dubiel, J. S., & Froelich, J. C. (1999) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199904000-00020 · Cited by 422 · see citing works
Juonala, M., Viikari, J. S. A., Laitinen, T. P., Marniemi, J., Helenius, H. Y. M., Rönnemaa, T., & Raitakari, O. T. (2004) · Circulation · doi:10.1161/01.cir.0000147540.88559.00 · Cited by 425 · see citing works
Metabolic Syndrome in Type 1 Diabetes
Thorn, L. M., Forsblom, C. M., Fagerudd, J. A., Thomas, M. C., Pettersson-Fernholm, K., Saraheimo, M., Wadén, J., Rönnback, M., Rosengård‐Bärlund, M., af Björkesten, C.-G., et al. (2005) · Diabetes Care · doi:10.2337/diacare.28.8.2019 · Cited by 424 · see citing works
Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy.
Booth, F., Chakravarthy, M., Gordon, S., & Spangenburg, E. (2002) · Journal of applied physiology · doi:10.1152/japplphysiol.00073.2002 · Cited by 467 · see citing works
“and insulin resistance are associated with blunted endothelium-dependent but not endothelium-independent vasodilation (9); furthermore, hyperinsulinemia fails to augment endothelium-dependent vasodilation (228); 2) patients with Type 1 or 2 diabetes have significant abnormalities in endothelial function (1); and 3) lo…”
BackgroundEndothelial Dysfunction in Obesity and Insulin Resistance: A Road to Diabetes and Heart Disease
Caballero, A. E. (2003) · Obesity Research · doi:10.1038/oby.2003.174 · Cited by 416 · see citing works
Obesity-Related Hypertension: Epidemiology, Pathophysiology, and Clinical Management
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Nonhypoglycemic Effects of Thiazolidinediones
Parulkar, A., Pendergrass, M., Granda-Ayala, R., Lee, T. R., & Fonseca, V. A. (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-134-1-200101020-00014 · Cited by 410 · see citing works
“Although the clinical significance of this observation is unclear, defects in nitric oxide synthesis are thought to be important in the pathogenesis of cardiovascular disease in persons with type 2 diabetes (11, 69, 70).”
BackgroundAbdominal obesity is associated with increased risk of acute coronary events in men
Lakka, H. (2002) · European Heart Journal · doi:10.1053/euhj.2001.2889 · Cited by 391 · see citing works
(Pre)diabetes, brain aging, and cognition
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The cardio-renal-metabolic connection: a review of the evidence
Marassi, M., & Fadini, G. P. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01937-x · Cited by 386 · see citing works
“Insulin resistance per se leads to peripheral microvascular dysfunction [58] and skeletal muscle dysfunction [59], both of which are linked to an increased risk of HF [60, 61].”
BackgroundHamburg, N. M., McMackin, C. J., Huang, A. L., Shenouda, S. M., Widlansky, M. E., Schulz, E., Gokce, N., Ruderman, N. B., Keaney, J. F., & Vita, J. A. (2007) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.153288 · Cited by 474 · see citing works
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Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production.
Steinberg, H. O., Paradisi, G., Brechtel, G., Crowder, K., Cronin, J., & Baron, A. (2000) · Diabetes · doi:10.2337/diabetes.49.7.1231 · Cited by 380 · see citing works
Tissue–Specific Insulin Signaling, Metabolic Syndrome, and Cardiovascular Disease
Rask‐Madsen, C., & Kahn, C. R. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.241919 · Cited by 376 · see citing works
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Federici, M., Menghini, R., Mauriello, A., Hribal, M. L., Ferrelli, F., Lauro, D., Sbraccia, P., Spagnoli, L. G., Sesti, G., & Lauro, R. (2002) · Circulation · doi:10.1161/01.cir.0000023043.02648.51 · Cited by 372 · see citing works
Role of Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic Syndrome Revisited
da Silva, A. A., do Carmo, J. M., Li, X., Wang, Z., Mouton, A. J., & Hall, J. E. (2020) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2020.02.066 · Cited by 381 · see citing works
Faggiano, A., Pivonello, R., Spiezia, S., De Martino, M. C., Filippella, M., Di Somma, C., Lombardi, G., & Colao, A. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021558 · Cited by 358 · see citing works
“(28), impairment of glucose tolerance (29), and gestational diabetes (30).”
BackgroundInflammation as a Link between Obesity and Metabolic Syndrome
Faloia, E., Grazia, M., Robertis, M. D., Luconi, M. P., Furlani, G., & Boscaro, M. (2012) · Journal of Nutrition and Metabolism · doi:10.1155/2012/476380 · Cited by 358 · see citing works
Review of Alterations in Endothelial Nitric Oxide Production in Diabetes
Pieper, G. M. (1998) · Hypertension · doi:10.1161/01.hyp.31.5.1047 · Cited by 353 · see citing works
Prognostic value of the metabolic syndrome in essential hypertension
Schillaci, G., Pirro, M., Vaudo, G., Gemelli, F., Marchesi, S., Porcellati, C., & Mannarino, E. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.12.049 · Cited by 352 · see citing works
Hypoadiponectinemia Is Closely Linked to Endothelial Dysfunction in Man
Shimabukuro, M., Higa, N., Asahi, T., Oshiro, Y., Takasu, N., Tagawa, T., Ueda, S., Shimomura, I., Funahashi, T., & Matsuzawa, Y. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021883 · Cited by 346 · see citing works
“Adiponectin (19, 29, 23) and FFA (6, 7), which are both secreted from adipocytes, may independently and bidirectionally regulate endothelial function through modulation of insulin sensitivity in the whole body and vascular beds.”
BackgroundInfluentialObesity and Body Fat Distribution Induce Endothelial Dysfunction by Oxidative Stress
Perticone, F., Ceravolo, R., Candigliota, M., Ventura, G., Iacopino, S., Sinopoli, F., & Mattioli, P. L. (2001) · Diabetes · doi:10.2337/diabetes.50.1.159 · Cited by 336 · see citing works
“Our data confirm and extend previous findings (19) that human obesity and its correlates of abdominal fat distribution and indexes of IR are inversely related to FBF in response to ACh.”
BackgroundResultInfluentialHamdy, O., Ledbury, S., Mullooly, C., Jarema, C., Porter, S., Ovalle, K., Moussa, A., Caselli, A., Caballero, A. E., Economides, P. A., et al. (2003) · Diabetes Care · doi:10.2337/diacare.26.7.2119 · Cited by 335 · see citing works
“Endothelial dysfunction, an early step in the development of atherosclerosis (5), has been reported in patients with type 2 diabetes (6) and in obese nondiabetic individuals (7).”
Vecchione, C., Maffei, A., Colella, S., Aretini, A., Poulet, R., Frati, G., Gentile, M. T., Fratta, L., Trimarco, V., Trimarco, B., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.1.168 · Cited by 331 · see citing works
“This pathological condition is associated with a high incidence of hypertension and cardiovascular complications (2,3), which have in turn been linked to both the activation of the sympathetic nervous system (4) and the impairment of endothelial function (5), two pivotal phenotypical traits of obese subjects.”
Montagnani, M., Golovchenko, I., Kim, I., Koh, G. Y., Goalstone, M. L., Mundhekar, A. N., Johansen, M. L., Kucik, D. F., Quon, M. J., & Draznin, B. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m103728200 · Cited by 328 · see citing works
Orio, F., Palomba, S., Cascella, T., Simone, B. D., Biase, S. D., Russo, T., Labella, D., Zullo, F., Lombardi, G., & Colao, A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031867 · Cited by 330 · see citing works
Shinozaki, K., Kashiwagi, A., Nishio, Y., Okamura, T., Yoshida, Y., Masada, M., Toda, N., & Kikkawa, R. (1999) · Diabetes · doi:10.2337/diabetes.48.12.2437 · Cited by 329 · see citing works
Rheumatoid Arthritis: A Disease Associated with Accelerated Atherogenesis
González-Gay, M. Á., González‐Juanatey, C., & Martin, J. J. (2005) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2005.03.004 · Cited by 329 · see citing works
Adiponectin actions in the cardiovascular system
Hopkins, T. A., Ouchi, N., Shibata, R., & Walsh, K. X. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.10.009 · Cited by 326 · see citing works
Lozano, I. I., der Werf, R. V., Bietiger, W., Seyfritz, E., Péronet, C., Pinget, M., Jeandidier, N., Maillard, É., Marchioni, E., Sigrist, S., et al. (2016) · Nutrition & Metabolism · doi:10.1186/s12986-016-0074-1 · Cited by 328 · see citing works
“In addition, a number of disorders may induce endothelial dysfunction, such as obesity, visceral fat distribution [57], impaired fasting glucose, hyperglycaemia [58], insulin resistance [59], oxidative stress [60], and inflammation [61] all of which were observed in our models, and reported in other studies [62].”
ResultInsulin Causes Endothelial Dysfunction in Humans: Sites and Mechanisms
Arcaro, G., Cretti, A., Balzano, S., Lechi, A., Muggeo, M., Bonora, E., & Bonadonna, R. C. (2002) · Circulation · doi:10.1161/hc0502.103333 · Cited by 407 · see citing works
Roberts, C. K., Barnard, R. J., Sindhu, R. K., Jurczak, M., Ehdaie, A., & Vaziri, N. D. (2006) · Metabolism · doi:10.1016/j.metabol.2006.02.022 · Cited by 322 · see citing works
“Metabolic syndrome, otherwise known as syndrome X or insulin resistance syndrome, is defined by the presence of insulin resistance, hyperinsulinemia, and some combination of obesity, dyslipidemia, inflammation, endothelial dysfunction, and hypertension [1-9].”
BackgroundInsulin Resistance and Atherosclerosis
Nigro, J., Osman, N., Dart, A. M., & Little, P. J. (2006) · Endocrine Reviews · doi:10.1210/er.2005-0007 · Cited by 316 · see citing works
“In insulin resistance, VSMCs have an impaired responsiveness to NO, resulting in increased contraction that can result in an imbalance in vascular tone and may impact on insulin-mediated delivery of glucose to muscle in the insulin-resistant state (96).”
BackgroundPotenza, M. A., Marasciulo, F. L., Chieppa, D. M., Brigiani, G. S., Formoso, G., Quon, M. J., & Montagnani, M. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00092.2005 · Cited by 314 · see citing works
“greater nutritive blood flow to skeletal muscle (53).”
BackgroundGonzález-Gay, M. Á., Matias, J. M. D., González‐Juanatey, C., Garcı́a-Porrúa, C., Sanchez-Andrade, A., Martin, J. J., & Llorca, J. (2006) · PubMed · Cited by 313 · see citing works
Woo, K. S., Chook, P., Yu, C. C.-W., Sung, R. Y. T., Qiao, M., Leung, S. S. F., Lam, C. W. K., Metreweli, C., & Celermajer, D. S. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802539 · Cited by 311 · see citing works
Obesity, Insulin Resistance, and the Metabolic Syndrome
Lteif, A. A., Han, K., & Mather, K. J. (2005) · Circulation · doi:10.1161/circulationaha.104.520130 · Cited by 305 · see citing works
Pathophysiological implications of insulin resistance on vascular endothelial function
Wheatcroft, S. B., Williams, I. L., Shah, A. M., & Kearney, M. T. (2003) · Diabetic Medicine · doi:10.1046/j.1464-5491.2003.00869.x · Cited by 307 · see citing works
Leptin and hyperleptinemia - from friend to foe for cardiovascular function
Ren, J. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1810001 · Cited by 305 · see citing works
“…activation of the sympathetic autonomic nervous system and impairment of endothelial function are the two pivotal phenotypical traits in obesity (Steinberg et al. 1996, Julius et al. 2000, Kuo et al. 2003), the cellular mechanisms responsible for sympathetic hyperactivity and endothelial…”
BackgroundRask‐Madsen, C., Li, Q., Freund, B., Feather, D., Abramov, R., Wu, I., Chen, K., Hiraoka‐Yamamoto, J., Goldenbogen, J., Sotiropoulos, K. B., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.03.013 · Cited by 304 · see citing works
“, 1999) and blunted vascular effects of insulin (Steinberg et al., 1996).”
BackgroundResultInfluentialObesity Blunts Insulin-Mediated Microvascular Recruitment in Human Forearm Muscle
Clerk, L. H., Keske, M. A., Jahn, L. A., Liu, Z., Lindner, J. R., & Barrett, E. J. (2006) · Diabetes · doi:10.2337/db05-1373 · Cited by 300 · see citing works
“Additionally, evidence from several (but not all [5]) studies indicates that obesity is associated with impaired endothelial function, as assessed by measurements of either responsiveness of resistance arterioles to infusion of cholinergic vasodilators (6) or flow-mediated conduit vessel relaxation (7).”
BackgroundMori, T. A., Bao, D. Q., Burke, V., Puddey, I. B., Watts, G. F., & Beilin, L. J. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/70.5.817 · Cited by 296 · see citing works
Tarkun, İ., ARSLAN, B., Cantürk, Z., Türemen, E., Şahı̇n, T., & Duman, C. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0751 · Cited by 297 · see citing works
Adolescent Obesity: Diet Quality, Psychosocial Health, and Cardiometabolic Risk Factors
Ruiz, L. D., Zuelch, M. L., Dimitratos, S. M., & Scherr, R. E. (2019) · Nutrients · doi:10.3390/nu12010043 · Cited by 311 · see citing works
Prevention of Type 2 Diabetes Mellitus Through Inhibition of the Renin-Angiotensin System
Scheen, A. J. (2004) · Drugs · doi:10.2165/00003495-200464220-00004 · Cited by 293 · see citing works
Human C-reactive protein and the metabolic syndrome
Devaraj, S., Singh, U. S., & Jialal, I. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32832ac03e · Cited by 291 · see citing works
Vascular dysfunction in diabetes mellitus
Feener, E. P., & King, G. L. (1997) · The Lancet · doi:10.1016/s0140-6736(97)90022-2 · Cited by 287 · see citing works
Obesity and hypertension: two epidemics or one?
Davy, K. P., & Hall, J. E. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00707.2003 · Cited by 280 · see citing works
“There is increasing evidence that obesity in humans is associated with peripheral (146) and coronary (6) endothelial dysfunction.”
BackgroundJonk, A. M., Houben, A. J. H. M., de Jongh, R. T., Serné, E. H., Schaper, N. C., & Stehouwer, C. D. A. (2007) · Physiology · doi:10.1152/physiol.00012.2007 · Cited by 279 · see citing works
“Obese subjects showed blunted vasodilation in response to classic endothelium-dependent vasodilators in skin and resistance arteries (24, 29, 101).”
BackgroundEndothelial inflammation in insulin resistance
Sjöholm, Å., & Nyström, T. (2005) · The Lancet · doi:10.1016/s0140-6736(05)17912-4 · Cited by 278 · see citing works
Role of endothelial dysfunction in insulin resistance
Hsueh, W. A., & Quiñones, M. J. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(03)00611-8 · Cited by 271 · see citing works
Prior, J. O., Quiñones, M. J., Hernandez‐Pampaloni, M., Facta, A. D., Schindler, T. H., Sayre, J. W., Hsueh, W. A., & Schelbert, H. R. (2005) · Circulation · doi:10.1161/01.cir.0000164232.62768.51 · Cited by 275 · see citing works
Insulin Resistance, Hyperinsulinemia, and Renal Injury: Mechanisms and Implications
Sarafidis, P., & Ruilope, L. (2006) · American Journal of Nephrology · doi:10.1159/000093632 · Cited by 296 · see citing works
“in a dose-dependent manner. In contrast, several other studies have documented that in insulin-resistant states, such as obesity [”
ResultRegulation of obesity and insulin resistance by nitric oxide
Sansbury, B. E., & Hill, B. G. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.05.016 · Cited by 274 · see citing works
“The fact that obesity in humans is associated with decreased blood flow in response to methacholine [230], bradykinin [231,232], substance P and acetylcholine [232], shear stress [233], and insulin [234,235] seems to suggest that the”
BackgroundType II Diabetes Abrogates Sex Differences in Endothelial Function in Premenopausal Women
Steinberg, H. O., Paradisi, G., Cronin, J., Crowde, K., Hempfling, A., Brechtel, G., & Baron, A. (2000) · Circulation · doi:10.1161/01.cir.101.17.2040 · Cited by 271 · see citing works
Antioxidants, diabetes and endothelial dysfunction
Laight, D. W. (2000) · Cardiovascular Research · doi:10.1016/s0008-6363(00)00054-7 · Cited by 264 · see citing works
Gilchrist, M., Winyard, P. G., Aizawa, K., Anning, C., Shore, A., & Benjamin, N. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.01.024 · Cited by 261 · see citing works
- Authors
- Steinberg, H. O., Chaker, H., Leaming, R., Johnson, A., Brechtel, G., & Baron, A. D.
- Affiliations
- Indiana University (US)
- Richard L. Roudebush VA Medical Center (US)
- Indiana University Hospital (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1996-06-01
- Volume
- 97
- Issue
- 11
- Pages
- 2601-2610
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507347
- OpenAlex
- W1982811953
- Cited by
- 1,687
- References
- 59
- Citations by year
- 2026: 11 · 2025: 23 · 2024: 17 · 2023: 30 · 2022: 19 · 2021: 32 · 2020: 30 · 2019: 36 · 2018: 36 · 2017: 46 · 2016: 50 · 2015: 51 · 2014: 69 · 2013: 69 · 2012: 61
- FWCI
- 18.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- American Heart Association
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK42469, P60DK020542, DK20542)
- National Center for Research Resources (M 01-RR750-19)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- obesity, insulin resistance, endothelial dysfunction, endothelium-dependent vasodilation, euglycemic hyperinsulinemia, leg blood flow, methacholine, sodium nitroprusside, type 2 diabetes, fat mass, atherosclerosis risk
- MeSH terms
- Adult, Blood Glucose, Blood Pressure, Cholesterol, Diabetes Mellitus, Type 2, Endothelium, Vascular, Fatty Acids, Nonesterified, Glucose, Humans, Hyperinsulinism, Infusions, Intra-Arterial, Infusions, Intravenous, Insulin, Insulin Resistance, Leg, Cholesterol, HDL, Cholesterol, LDL, Nitroprusside, Obesity, Reference Values, Regional Blood Flow, Syndrome, Time Factors, Triglycerides, Vasodilation, Glucose Clamp Technique, Body Mass Index, Methacholine Chloride
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