The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972) · Clinical Chemistry · doi:10.1093/clinchem/18.6.499 · Cited by 32,423
Role of Insulin Resistance in Human Disease
Reaven, G. M. (1988) · Diabetes · doi:10.2337/diab.37.12.1595 · Cited by 12,154
Antihyperlipidemic and Biochemical Activities of Mcy Protein in Streptozotocin Induced Diabetic Rats
Marella, S., Maddirela, D. R., Badri, K. R., Kumar, M. V. J., & Chippada, A. R. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373954 · Cited by 5,938
Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance.
National Diabetes Data Group (1979) · Diabetes · doi:10.2337/diab.28.12.1039 · Cited by 4,909
Abnormal Endothelium-Dependent Vascular Relaxation in Patients with Essential Hypertension
Panza, J. A., Quyyumi, A. A., Brush, J. E., & Epstein, S. E. (1990) · New England Journal of Medicine · doi:10.1056/nejm199007053230105 · Cited by 2,366
Insulin Resistance in Essential Hypertension
Ferrannini, E., Buzzigoli, G., Bonadonna, R., Giorico, M. A., Oleggini, M., Graziadei, L., Pedrinelli, R., Brandi, L., & Bevilacqua, S. (1987) · New England Journal of Medicine · doi:10.1056/nejm198708063170605 · Cited by 2,344
Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man
Vallance, P., Collier, J., & Moncada, S. (1989) · The Lancet · doi:10.1016/s0140-6736(89)91013-1 · Cited by 1,590
Steinberg, H. O., Brechtel, G., Johnson, A., Fineberg, N. S., & Baron, A. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117433 · Cited by 1,216
Radomski, M. W., Palmer, R. M. J., & Moncada, S. (1987) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1987.tb11367.x · Cited by 1,158
Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus.
Johnstone, M. T., Creager, S. J., Scales, K. M., Cusco, J. A., Lee, B. K., & Creager, M. A. (1993) · Circulation · doi:10.1161/01.cir.88.6.2510 · Cited by 1,117
Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans.
Anderson, E. A., Hoffman, R. P., Balon, T. W., Sinkey, C. A., & Mark, A. L. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115260 · Cited by 1,075
Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans.
Creager, M. A., Cooke, J. P., Mendelsohn, M. E., Gallagher, S. J., Coleman, S. M., Loscalzo, J., & Dzau, V. J. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114688 · Cited by 1,017
Laakso, M., Edelman, S. V., Brechtel, G., & Baron, A. D. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114644 · Cited by 930
Self-citationMcVeigh, G. E., Brennan, G. M., Johnston, G. D., McDermott, B. J., McGrath, L. T., Henry, W. R., Andrews, J. W., & Hayes, J. R. (1992) · Diabetologia · doi:10.1007/bf00429099 · Cited by 916
Role of Insulin Resistance in Human Disease (Syndrome X): An Expanded Definition
Reaven, G. M. (1993) · Annual Review of Medicine · doi:10.1146/annurev.me.44.020193.001005 · Cited by 908
Role of Insulin Resistance in Human Disease
Reaven, G. M. (1992) · Medical science symposia series · doi:10.1007/978-94-011-2700-4_10 · Cited by 895
L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans.
Creager, M. A., Gallagher, S. J., Girerd, X. J., Coleman, S. M., Dzau, V. J., & Cooke, J. P. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115987 · Cited by 809
Nitric oxide release accounts for insulin's vascular effects in humans.
Scherrer, U., Randin, D., Vollenweider, P., Vollenweider, L., & NICOD, P. H. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117621 · Cited by 752
Aging and Endothelial Function in Normotensive Subjects and Patients With Essential Hypertension
Taddei, S., Virdis, A., Mattei, P., Ghiadoni, L., Gennari, A., Fasolo, C. B., Sudano, I., & Salvetti, A. (1995) · Circulation · doi:10.1161/01.cir.91.7.1981 · Cited by 718
Panza, J. A., Casino, P. R., Kilcoyne, C. M., & Quyyumi, A. A. (1993) · Circulation · doi:10.1161/01.cir.87.5.1468 · Cited by 707
Dose-response characteristics for effects of insulin on production and utilization of glucose in man
Rizza, R. A., Mandarino, L. J., & Gerich, J. E. (1981) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1981.240.6.e630 · Cited by 705
Reaven, G. M., Chen, Y. I., Jeppesen, J., Maheux, P., & Krauss, R. M. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116541 · Cited by 687
Mechanisms of insulin resistance in human obesity: evidence for receptor and postreceptor defects.
Kolterman, O. G., Insel, J., Saekow, M., & Olefsky, J. M. (1980) · Journal of Clinical Investigation · doi:10.1172/jci109790 · Cited by 664
Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans
Baron, A., Brechtel, G., Wallace, P., & Edelman, S. V. (1988) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1988.255.6.e769 · Cited by 645
Colorimetric ultramicro method for the determination of free fatty acids
Novák, M. (1965) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39315-9 · Cited by 639
Chait, A., Brazg, R., Tribble, D. L., & Krauss, R. M. (1993) · The American Journal of Medicine · doi:10.1016/0002-9343(93)90144-e · Cited by 554
Oxidized Low-density Lipoprotein Decreases the Expression of Endothelial Nitric Oxide Synthase
Liao, J. K., Shin, W. S., Lee, W. Y., & Clark, S. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.1.319 · Cited by 543
Calver, A., Collier, J., & Vallance, P. J. (1992) · Journal of Clinical Investigation · doi:10.1172/jci116149 · Cited by 522
Nitric oxide. A novel signal transduction mechanism for transcellular communication.
Ignarro, L. J. (1990) · Hypertension · doi:10.1161/01.hyp.16.5.477 · Cited by 498
The discovery of nitric oxide as the endogenous nitrovasodilator.
Moncada, S., Palmer, R. M. J., & Higgs, E. A. (1988) · Hypertension · doi:10.1161/01.hyp.12.4.365 · Cited by 496
Impaired Insulin-Mediated Skeletal Muscle Blood Flow in Patients With NIDDM
Laakso, M., Edelman, S. V., Brechtel, G., & Baron, A. D. (1992) · Diabetes · doi:10.2337/diab.41.9.1076 · Cited by 470
Inactivation of endothelial derived relaxing factor by oxidized lipoproteins.
Chin, J. H., Azhar, S., & Hoffman, B. B. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115549 · Cited by 447
Panza, J. A., García, C. E., Kilcoyne, C. M., Quyyumi, A. A., & Cannon, R. O. (1995) · Circulation · doi:10.1161/01.cir.91.6.1732 · Cited by 428
Inhibition of low‐density lipoprotein oxidation by nitric oxide Potential role in atherogenesis
Hogg, N., Kalyanaraman, B., Joseph, J., Struck, A. T., & Parthasarathy, S. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)81706-6 · Cited by 400
Skeletal muscle blood flow. A possible link between insulin resistance and blood pressure.
Baron, A., Brechtel, G., Johnson, A., & Hardin, D. S. (1993) · Hypertension · doi:10.1161/01.hyp.21.2.129 · Cited by 362
Calver, A., Collier, J., Moncada, S., & Vallance, P. J. (1992) · PubMed · Cited by 332
Panza, J. A., Casino, P. R., Badar, D. M., & Quyyumi, A. A. (1993) · Circulation · doi:10.1161/01.cir.87.5.1475 · Cited by 285
Oleic Acid Inhibits Endothelial Nitric Oxide Synthase by a Protein Kinase C–Independent Mechanism
Davda, R. K., Stepniakowski, K. T., Lü, G., Ullian, M. E., Goodfriend, T. L., & Egan, B. M. (1995) · Hypertension · doi:10.1161/01.hyp.26.5.764 · Cited by 216
Ferri, C., Pittoni, V., Piccoli, A., Laurenti, O., Cassone, M., Bellini, C., Properzi, G., Valesini, G., MATTIA, G. D., & Santucci, A. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.3.7883838 · Cited by 205
Skeletal muscle blood flow independently modulates insulin-mediated glucose uptake
Baron, A., Steinberg, H. O., Brechtel, G., & Johnson, A. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.2.e248 · Cited by 200
Insulin differentially regulates systemic and skeletal muscle vascular resistance
Baron, A., & Brechtel, G. (1993) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1993.265.1.e61 · Cited by 179
Impaired insulin-mediated skeletal muscle blood flow in patients with NIDDM
Laakso, M., Edelman, S. V., Brechtel, G., et al. (1992) · Diabetes · doi:10.2337/diabetes.41.9.1076 · Cited by 145
Self-citationFatty Acids Enhance Vascular α-Adrenergic Sensitivity
Stepniakowski, K. T., Goodfriend, T. L., & Egan, B. M. (1995) · Hypertension · doi:10.1161/01.hyp.25.4.774 · Cited by 130
Groop, L., Bonadonna, R. C., Simonson, D. C., Petrides, A. S., shank, M. L., & DeFronzo, R. A. (1992) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1992.263.1.e79 · Cited by 128
Stimulation of vascular Na(+)-K(+)-ATPase activity by nitric oxide: a cGMP-independent effect
Gupta, S., McArthur, C., Grady, C., & Ruderman, N. B. (1994) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1994.266.5.h2146 · Cited by 118
Inhibition of low-density lipoprotein oxidation by nitric oxide
Hogg, N., Parthasarthy, S., & Kalyanaraman, B. (1993) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(93)90278-3 · Cited by 115
Circulating Endothelin-1 Levels Increase During Euglycemic, Hyperinsulinemic Clamp in Lean NIDDM Men
Ferri, C., Carlomagno, A., Coassin, S., Baldoncini, R., Cassone-Faldetta, M., Laurenti, O., Properzi, G., Santucci, A., & Mattia, G. D. (1995) · Diabetes Care · doi:10.2337/diacare.18.2.226 · Cited by 92
Mollace, V., Salvemini, D., Änggård, E., & Vane, J. R. (1991) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1991.tb12481.x · Cited by 88
Role of Insulin Resistance in Human Disease (syndrome X): An Expanded Definition
Reaven, G. (1993) · Annual Review of Medicine · doi:10.1146/annurev.med.44.1.121 · Cited by 84
Insulin Resistance in Secondary Hypertension
Shamiss, A., Carroll, J., & Rosenthal, T. (1992) · American Journal of Hypertension · doi:10.1093/ajh/5.1.26 · Cited by 74
Dustan, H. P. (1985) · Annals of Internal Medicine · doi:10.7326/0003-4819-103-6-1047 · Cited by 72
Endothelium-Dependent Regulation of Resistance Arteries
Lüscher, T. F., Dohi, Y., & Tschudi, M. R. (1992) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199200195-00006 · Cited by 72
Jessup, W., & Dean, R. T. (1993) · Atherosclerosis · doi:10.1016/0021-9150(93)90111-7 · Cited by 57
Takahashi, H., Nakanishi, T., Nishimura, M., Tanaka, H., & Yoshimura, M. (1992) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199204002-00061 · Cited by 57
Haffner, S. M., Mitchell, B. D., Valaez, R. A., Hazuaa, H. P., Morales, P. A., & D, M. P. S. M. (1992) · American Journal of Hypertension · doi:10.1093/ajh/5.3.147 · Cited by 53
Age-related changes in release of endothelium-derived relaxing factor from the carotid artery.
Paternò, R., Faraci, F. M., & Heistad, D. D. (1994) · Stroke · doi:10.1161/01.str.25.12.2457 · Cited by 32
Endothelium-derived relaxing factor (nitric oxide), lipoprotein oxidation and atherosclerosis
Bruckdorfer, K. R., JACOBS, M., & Rice-Evans, C. A. (1990) · Biochemical Society Transactions · doi:10.1042/bst0181061 · Cited by 28
Björntorp, P. A. (1990) · Clinical and Experimental Hypertension · doi:10.3109/10641969009073499 · Cited by 20
Cellular modification of low-density lipoproteins
Jessup, W. (1993) · Biochemical Society Transactions · doi:10.1042/bst0210321 · Cited by 15
Functional Abnormalities of the Vascular Endothelium in Hypertension and Atherosclerosis
Lüscher, T. F. (1990) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365519009090539 · Cited by 9
Functional Abnormalities of the Vascular Endothelium in Hypertension and Atherosclerosis
Lüscher, T. F. (1990) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365519009090539 · Cited by 4
Flagged first, then by citations
Research works printed but not linked: 1
- Brozek, J., and A. Henschel. 1961. Techniques for measuring body com- position: proceedings of a conference. In Conference on Techniques for Mea- suring Body Composition. National Academy of Sciences, National Research Council. Washington DC. 78-89.
Cited by
Sorted by citations
Endothelial cells in physiology and in the pathophysiology of vascular disorders.
Cines, D. B., Pollak, E. S., Buck, C. A., Loscalzo, J., Zimmerman, G. A., McEver, R. P., Pober, J. S., Wick, T. M., Konkle, B. A., Schwartz, B. S., et al. (1998) · PubMed · doi:10.1182/blood.v91.10.3527 · Cited by 2,246
The clinical implications of endothelial dysfunction
Widlansky, M. E., Gokce, N., Keaney, J. F., & Vita, J. A. (2003) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(03)00994-x · Cited by 1,749
“Recent examples of the utility of endothelial function in regard to novel risk factors include obesity (6) and certain systemic infections (8).”
BackgroundKinaan, M., Ding, H., & Triggle, C. R. (2015) · Medical Principles and Practice · doi:10.1159/000381643 · Cited by 1,515
Metabolic Effects of Fructose and the Worldwide Increase in Obesity
Tappy, L., & Lê, K.-A. (2010) · Physiological Reviews · doi:10.1152/physrev.00019.2009 · Cited by 1,256
The Assessment of Endothelial Function
Flammer, A. J., Anderson, T. J., Celermajer, D. S., Creager, M. A., Deanfield, J. E., Ganz, P., Hamburg, N. M., Lüscher, T. F., Shechter, M., Taddei, S., et al. (2012) · Circulation · doi:10.1161/circulationaha.112.093245 · Cited by 1,157
Metadata
- 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 (medical) › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
