Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation
Open accessAbstract
We have recently shown that insulin-resistant obese subjects exhibit impaired endothelial function. Here, we test the hypothesis that elevation of circulating FFA to levels seen in insulin-resistant subjects can impair endothelial function. We studied leg blood flow responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (Mch) or the endothelium-independent vasodilator sodium nitroprusside during the infusion of saline and after raising systemic circulating FFA levels exogenously via a low- or high-dose infusion of Intralipid plus heparin or endogenously by an infusion of somatostatin (SRIF) to produce insulinopenia in groups of lean healthy humans. After 2 h of infusion of Intralipid plus heparin, FFA levels increased from 562+/-95 to 1,303+/-188 micromol, and from 350+/-35 to 3,850+/-371 micromol (P < 0.001) vs. saline for both low- and high-dose groups, respectively. Mch-induced vasodilation relative to baseline was reduced by approximately 20% in response to the raised FFA levels in both groups (P < 0.05, saline vs. FFA, ANOVA). In contrast, similar FFA elevation did not change leg blood flow responses to sodium nitroprusside. During the 2-h SRIF infusion, insulin levels fell, and FFA levels rose from 474+/-22 to 1,042+/-116 micromol (P < 0.01); Mch-induced vasodilation was reduced by approximately 20% (P < 0.02, saline vs. SRIF, ANOVA). Replacement of basal insulin levels during SRIF resulted in a fall of FFA levels from 545+/-47 to 228+/-61 micromol, and prevented the impairment of Mch-induced vasodilation seen with SRIF alone. In conclusion, (a) elevated circulating FFA levels cause endothelial dysfunction, and (b) impaired endothelial function in insulin-resistant humans may be secondary to the elevated FFA concentrations observed in these patients.
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
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?
Experimental induction of insulin resistance in rats and in humans resulted in reductions in blood flow responses.
“The experimental induction of IR in rats (31) and in humans (7) resulted in reductions in blood flow responses.”
From Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus (2001) · cites this paper as [7]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Steinberg, H. O., Chaker, H., Leaming, R., Johnson, A., Brechtel, G., & Baron, A. D. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118709 · Cited by 1,687 · cited 10× · see citing works
“We found, however, that serum cholesterol and blood pressure elevations could account for only a small proportion of the endothelial dysfunction displayed in these subjects (4).”
BackgroundResultInfluentialSelf-citationSteinberg, H. O., Brechtel, G., Johnson, A., Fineberg, N. S., & Baron, A. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117433 · Cited by 1,216 · see citing works
Self-citationLaakso, M., Edelman, S. V., Brechtel, G., & Baron, A. D. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114644 · Cited by 930 · see citing works
Self-citationRates 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 · see citing works
Self-citationColorimetric 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 · see citing works
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 · cited 1× · see citing works
“Interestingly, this insulin effect is either blunted or absent in obese insulin-resistant subjects with or without non-insulin-dependent diabetes mellitus (NIDDM) 1 (1, 3).”
BackgroundSelf-citationTHE VASCULAR BIOLOGY OF NITRIC OXIDE AND ITS ROLE IN ATHEROGENESIS
Lloyd‐Jones, D. M., & Bloch, K. D. (1996) · Annual Review of Medicine · doi:10.1146/annurev.med.47.1.365 · Cited by 243 · see citing works
Reaven, G. M. (1994) · PubMed · Cited by 241 · see citing works
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 · see citing works
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 · see citing works
Fatty 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 · see citing works
Pressor Effects of Portal Venous Oleate Infusion
Grekin, R. J., Vollmer, A. P., & Sider, R. S. (1995) · Hypertension · doi:10.1161/01.hyp.26.1.193 · Cited by 116 · see citing works
Rates of noninsulin-mediated glucose uptake are elevated in type II diabetic subjects.
Baron, A., Kolterman, O., Bell, J., Mandarino, L. J., & Olefsky, J. M. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112169 · Cited by 113 · see citing works
Self-citationSwislocki, A., Chen, Y. I., Golay, A., Chang, M. O., & Reaven, M. S. (1987) · Diabetologia · doi:10.1007/bf00277318 · Cited by 103 · see citing works
Time dependence of the interaction between lipid and glucose in humans
Bonadonna, R. C., Zych, K., Boni, C. D., Ferrannini, E., & DeFronzo, R. A. (1989) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1989.257.1.e49 · Cited by 101 · see citing works
Bruce, R., Godsland, I., Walton, C., Crook, D., & Wynn, V. (1994) · Metabolism · doi:10.1016/0026-0495(94)90222-4 · Cited by 32 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms, Pathophysiology, and Therapy of Arterial Stiffness
Zieman, S. J., Melenovsky, V., & Kass, D. A. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000160548.78317.29 · Cited by 1,854 · see citing works
Capes, S. E., Hunt, D., Malmberg, K., Pathak, P., & Gerstein, H. C. (2001) · Stroke · doi:10.1161/hs1001.096194 · Cited by 1,824 · see citing works
Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?
Yudkin, J. S., Kumari, M., Humphries, S. E., & Mohamed-Ali, V. (2000) · Atherosclerosis · doi:10.1016/s0021-9150(99)00463-3 · Cited by 1,775 · see citing works
Dyslipidemia in obesity: Mechanisms and potential targets
Klop, B., Elte, J., & Cabezas, M. (2013) · Nutrients · doi:10.3390/nu5041218 · Cited by 1,665 · see citing works
“This phenomenon may take place by elevated levels of FFA [72], which are generated by the action of LPL mediated lipolysis.”
BackgroundCreager, M. A., Lüscher, T. F., of, P. W. T. A., Cosentino, F., & Beckman, J. A. (2003) · Circulation · doi:10.1161/01.cir.0000091257.27563.32 · Cited by 1,654 · see citing works
Inoguchi, T., Li, P., Umeda, F., Yu, H. Y., Kakimoto, M., Imamura, M., Aoki, T., Etoh, T., Hashimoto, T., Naruse, M., et al. (2000) · Diabetes · doi:10.2337/diabetes.49.11.1939 · Cited by 1,577 · see citing works
Insulin resistance and cardiovascular disease
Ginsberg, H. N. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10762 · Cited by 1,358 · see citing works
Adipokines: molecular links between obesity and atheroslcerosis
Lau, D., Dhillon, B., Yan, H., Szmitko, P. E., & Verma, S. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01058.2004 · Cited by 930 · see citing works
DeFronzo, R. A. (2010) · Diabetologia · doi:10.1007/s00125-010-1684-1 · Cited by 889 · see citing works
Boden, G. H. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.06.007 · Cited by 852 · see citing works
Obesity, insulin resistance and free fatty acids
Boden, G. (2011) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0b013e3283444b09 · Cited by 848 · see citing works
Endothelial dysfunction — A major mediator of diabetic vascular disease
Sena, C. M., Pereira, A. M., & Seiça, R. M. F. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.08.006 · Cited by 796 · see citing works
Kaur, R., Kaur, M., & Singh, J. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0763-3 · Cited by 766 · see citing works
Stehouwer, C. D. A., Gall, M.-A., Twisk, J. W. R., Knudsen, E., Emeis, J. J., & Parving, H.-H. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1157 · Cited by 652 · see citing works
Diabetes and Endothelial Dysfunction: A Clinical Perspective
Calles-Escandón, J., & Cipolla, M. J. (2001) · Endocrine Reviews · doi:10.1210/edrv.22.1.0417 · Cited by 657 · see citing works
Tripathy, D., Mohanty, P., Dhindsa, S., Syed, T., Ghanim, H., Aljada, A., & Dandona, P. (2003) · Diabetes · doi:10.2337/diabetes.52.12.2882 · Cited by 658 · see citing works
Sandesara, P. B., Virani, S. S., Fazio, S., & Shapiro, M. D. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00184 · Cited by 626 · see citing works
Free Fatty Acids and Pathogenesis of Type 2 Diabetes Mellitus
Bergman, R. N., & Ader, M. (2000) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(00)00323-4 · Cited by 622 · see citing works
Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women
Modena, M. G., Bonetti, L., Coppi, F., Bursi, F., & Rossi, R. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)01976-9 · Cited by 573 · see citing works
Endothelial dysfunction in diabetes mellitus.
Hadi, H. A. R., & Suwaidi, J. M. S. A. (2007) · Europe PMC (PubMed Central) · Cited by 568 · see citing works
Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents
Di Pino, A., & DeFronzo, R. A. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00141 · Cited by 535 · see citing works
Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies
Mazzone, T., Chait, A., & Plutzky, J. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60768-0 · Cited by 545 · see citing works
Effect of Metformin and Rosiglitazone Combination Therapy in Patients With Type 2 Diabetes Mellitus
Fonseca, V. A., Rosenstock, J., Patwardhan, R., & Salzman, A. (2000) · JAMA · doi:10.1001/jama.283.13.1695 · Cited by 538 · 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
Early Life Origins of Insulin Resistance and Type 2 Diabetes in India and Other Asian Countries
Yajnik, C. S. (2004) · Journal of Nutrition · doi:10.1093/jn/134.1.205 · Cited by 491 · see citing works
Mechanisms 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
Palombo, C., & Kozàkovà, M. (2015) · Vascular Pharmacology · doi:10.1016/j.vph.2015.11.083 · Cited by 477 · see citing works
Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats
Rivera, L., Morón, R., Sánchez, M., Zarzuelo, A., & Galisteo, M. (2008) · Obesity · doi:10.1038/oby.2008.315 · Cited by 473 · 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
Assessment and treatment of endothelial dysfunction in humans
Anderson, T. J. (1999) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(99)00259-4 · Cited by 443 · see citing works
Peripheral artery disease in patients with diabetes: Epidemiology, mechanisms, and outcomes
Thiruvoipati, T. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i7.961 · Cited by 443 · see citing works
Inoguchi, T., Sonta, T., Tsubouchi, H., Etoh, T., Kakimoto, M., Sonoda, N., Sato, N., Sekiguchi, N., Kobayashi, K., Sumimoto, H., et al. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000077407.90309.65 · Cited by 435 · see citing works
Role of free fatty acids in endothelial dysfunction
Ghosh, A., Gao, L., Thakur, A., Siu, P. M., & Lai, C. W. K. (2017) · Journal of Biomedical Science · doi:10.1186/s12929-017-0357-5 · Cited by 418 · see citing works
de Jongh, R. T., Serné, E. H., IJzerman, R. G., de Vries, G., & Stehouwer, C. D. A. (2004) · Circulation · doi:10.1161/01.cir.0000129772.26647.6f · Cited by 407 · see citing works
Pancreatic Fat Content and β-Cell Function in Men With and Without Type 2 Diabetes
Tushuizen, M. E., Bunck, M. C. M., Pouwels, P. J. W., Bontemps, S., van Waesberghe, J. H. T., Schindhelm, R. K., Mari, A., Heine, R. J., & Diamant, M. (2007) · Diabetes Care · doi:10.2337/dc07-0326 · Cited by 402 · see citing works
Rivera, L., Morón, R., Zarzuelo, A., & Galisteo, M. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.11.027 · Cited by 391 · see citing works
Arterial stiffness: a brief review
Shirwany, N. A., & Zou, M. (2010) · Acta Pharmacologica Sinica · doi:10.1038/aps.2010.123 · Cited by 387 · see citing works
Adipose Tissue and Atherosclerosis
Fantuzzi, G., & Mazzone, T. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.106.131755 · Cited by 380 · see citing works
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
Self-citationOmega-3 fatty acids and metabolic syndrome: Effects and emerging mechanisms of action
Poudyal, H., Panchal, S. K., Diwan, V., & Brown, L. (2011) · Progress in Lipid Research · doi:10.1016/j.plipres.2011.06.003 · Cited by 373 · see citing works
Obesity hypertension: role of leptin and sympathetic nervous system
Hall, J. E. (2001) · American Journal of Hypertension · doi:10.1016/s0895-7061(01)02077-5 · Cited by 361 · 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
Du, X., Edelstein, D., Obici, S., Higham, N., Zou, M., & Brownlee, M. (2006) · Journal of Clinical Investigation · doi:10.1172/jci23354 · Cited by 344 · see citing works
Vascular function, insulin resistance and fatty acids
Steinberg, H. O., & Baron, A. (2002) · Diabetologia · doi:10.1007/s00125-002-0800-2 · Cited by 339 · see citing works
Self-citationHemostasis, endothelial stress, inflammation, and the metabolic syndrome
Grandl, G., & Wolfrum, C. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-017-0666-5 · Cited by 344 · see citing works
Wang, L., Gill, R., Pedersen, T. L., Higgins, L. J., Newman, J. W., & Rutledge, J. C. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m700505-jlr200 · Cited by 303 · see citing works
Free Fatty Acid Impairment of Nitric Oxide Production in Endothelial Cells Is Mediated by IKKβ
Kim, F., Tysseling, K. A., Rice, J., Pham, M., Haji, L., Gallis, B. M., Baas, A. S., Paramsothy, P., Giachelli, C. M., Corson, M. A., et al. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000160549.60980.a8 · Cited by 307 · 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
Cardiovascular Disease in Type 2 Diabetes From Population to Man to Mechanisms
Laakso, M. (2010) · Diabetes Care · doi:10.2337/dc09-0749 · Cited by 299 · see citing works
Emerging Roles of Vascular Endothelium in Metabolic Homeostasis
Pi, X., Xie, L., & Patterson, C. (2018) · Circulation Research · doi:10.1161/circresaha.118.313237 · Cited by 299 · see citing works
Jonk, 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
Black, P. H. (2006) · Medical Hypotheses · doi:10.1016/j.mehy.2006.04.008 · Cited by 276 · 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
Mechanistic Links Between Obesity, Diabetes, and Blood Pressure: Role of Perivascular Adipose Tissue
Saxton, S. N., Clark, B., Withers, S., Eringa, E. C., & Heagerty, A. M. (2019) · Physiological Reviews · doi:10.1152/physrev.00034.2018 · Cited by 277 · see citing works
The role of virgin olive oil components in the modulation of endothelial function
Perona, J. S., Cabello-Moruno, R., & Ruíz-Gutiérrez, V. (2005) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2005.11.007 · Cited by 278 · see citing works
Regulation 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
“[180], isolated arteries [181], animal models [182], and humans [183,184] and this is probably due to decreased PI3K–Akt-”
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
Self-citationSchernthaner, G., Matthews, D. R., Charbonnel, B. H., Markolf Hanefeld, E., & Brunetti, P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030861 · Cited by 268 · see citing works
Microvascular Function Relates to Insulin Sensitivity and Blood Pressure in Normal Subjects
Serné, E. H., Stehouwer, C. D. A., ter Maaten, J. C., ter Wee, P. M., Rauwerda, H., Donker, A. J. M., & Gans, R. O. B. (1999) · Circulation · doi:10.1161/01.cir.99.7.896 · Cited by 261 · see citing works
Endothelial dysfunction in obesity
Engin, A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_15 · Cited by 255 · see citing works
Lindsberg, P. J., & Roine, R. O. (2004) · Stroke · doi:10.1161/01.str.0000115297.92132.84 · Cited by 246 · see citing works
Brook, R. D., Bard, R. L., Rubenfire, M., Ridker, P. M., & Rajagopalan, S. (2001) · The American Journal of Cardiology · doi:10.1016/s0002-9149(01)02088-4 · Cited by 244 · see citing works
Williams, I. L., Wheatcroft, S. B., Shah, A. M., & Kearney, M. T. (2002) · International Journal of Obesity · doi:10.1038/sj.ijo.0801995 · Cited by 261 · see citing works
Insulin resistance and the endothelium
Hsueh, W. A., Lyon, C. J., & Quiñones, M. J. (2004) · The American Journal of Medicine · doi:10.1016/j.amjmed.2004.02.042 · Cited by 234 · see citing works
Donati, G., Stagni, B., Piscaglia, F., Venturoli, N., Morselli‐Labate, A. M., Rasciti, L., & Bolondi, L. (2004) · Gut · doi:10.1136/gut.2003.027086 · Cited by 231 · see citing works
Wang, X. L., Zhang, L., Youker, K. A., Zhang, M., Wang, J., LeMaire, S. A., Coselli, J. S., & Shen, Y. H. (2006) · Diabetes · doi:10.2337/db05-1574 · Cited by 230 · see citing works
Pistrosch, F., Passauer, J., Fischer, S., Fuecker, K., Hanefeld, M., & Gross, P. A. (2004) · Diabetes Care · doi:10.2337/diacare.27.2.484 · Cited by 225 · see citing works
PPARα deficiency reduces insulin resistance and atherosclerosis in apoE-null mice
Tordjman, K. M., Bernal‐Mizrachi, C., Zemany, L., Weng, S., Chu, F., Zhang, F., Leone, T. C., Coleman, T., Kelly, D. P., & Semenkovich, C. F. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11497 · Cited by 228 · see citing works
Dynamic of Hyperglycemia as a Predictor of Stroke Outcome in the ECASS-II Trial
Yong, M., & Kaste, M. (2008) · Stroke · doi:10.1161/strokeaha.108.514307 · Cited by 227 · see citing works
The postprandial effect of components of the mediterranean diet on endothelial function
Vogel, R. A., Corretti, M. C., & Plotnick, G. D. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)00896-2 · Cited by 223 · see citing works
Aneja, A. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.169 · Cited by 217 · see citing works
Insulin Resistance as a Link between Amyloid-Beta and Tau Pathologies in Alzheimer’s Disease
Mullins, R. J., Diehl, T. C., Chia, C. W., & Kapogiannis, D. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00118 · Cited by 217 · see citing works
Adipose tissue and the insulin resistance syndrome
Frayn, K. N. (2001) · Proceedings of The Nutrition Society · doi:10.1079/pns200195 · Cited by 215 · see citing works
Visceral and Subcutaneous Fat Quality and Cardiometabolic Risk
Rosenquist, K. J., Pedley, A., Massaro, J. M., Therkelsen, K. E., Murabito, J. M., Hoffmann, U., & Fox, C. S. (2013) · JACC. Cardiovascular imaging · doi:10.1016/j.jcmg.2012.11.021 · Cited by 216 · see citing works
Dagher, Z., Ruderman, N. B., Tornheim, K., & Ido, Y. (2001) · Circulation Research · doi:10.1161/hh1201.092998 · Cited by 209 · see citing works
Impaired endothelial function following a meal rich in used cooking fat
Williams, M. J. A., Sutherland, W. H. F., McCormick, M. P., de Jong, S. A., Walker, R. J., & WILKINS, G. T. (1999) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(98)00681-0 · Cited by 202 · see citing works
Insulin Resistance and Atherosclerosis
Razani, B., Chakravarthy, M. V., & Semenkovich, C. F. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.05.001 · Cited by 200 · see citing works
Natali, A., Toschi, E., Baldeweg, S. E., Ciociaro, D., Favilla, S., Saccà, L., & Ferrannini, E. (2006) · Diabetes · doi:10.2337/diabetes.55.04.06.db05-1076 · Cited by 198 · see citing works
Pilz, S., Scharnagl, H., Tiran, B., Seelhorst, U., Wellnitz, B., Boehm, B. O., Schaefer, J. R., & März, W. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0195 · Cited by 199 · see citing works
Inoue, I., Shino, K., Noji, S., Awata, T., & Katayama, S. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8622 · Cited by 199 · see citing works
Thematic review series: Patient-Oriented Research. Free fatty acid metabolism in human obesity
Koutsari, C., & Jensen, M. D. (2006) · Journal of Lipid Research · doi:10.1194/jlr.r600011-jlr200 · Cited by 198 · see citing works
Free Fatty Acid Levels Modulate Microvascular Function
de Jongh, R. T., Serné, E. H., IJzerman, R. G., de Vries, G., & Stehouwer, C. D. A. (2004) · Diabetes · doi:10.2337/diabetes.53.11.2873 · Cited by 195 · see citing works
Pathogenesis and pathophysiology of the cardiometabolic syndrome
Kirk, E. P., & Klein, S. (2009) · The Journal of Clinical Hypertension · doi:10.1111/j.1559-4572.2009.00054.x · Cited by 195 · see citing works
Chinen, I., Shimabukuro, M., Yamakawa, K., Higa, N., Matsuzaki, T., Noguchi, K., Ueda, S., Sakanashi, M., & Takasu, N. (2006) · Endocrinology · doi:10.1210/en.2006-1132 · Cited by 187 · see citing works
Leiter, L. A., FITCHETT, D. H., Gilbert, R. E., Gupta, M., Mancini, G. B. J., McFarlane, P. A., Ross, R., Teoh, H., Verma, S., Anand, S. S., et al. (2011) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2010.12.054 · Cited by 184 · see citing works
The Insulin Resistance Epidemic in India: Fetal Origins, Later Lifestyle, or Both?
Yajnik, C. S. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.2001.tb01898.x · Cited by 186 · see citing works
Vascular Effects of Improving Metabolic Control With Metformin or Rosiglitazone in Type 2 Diabetes
Natali, A., Baldeweg, S. E., Toschi, E., Capaldo, B., Barbaro, D., Gastaldelli, A., Yudkin, J. S., & Ferrannini, E. (2004) · Diabetes Care · doi:10.2337/diacare.27.6.1349 · Cited by 180 · see citing works
Yajnik, C. S. (2002) · Obesity Reviews · doi:10.1046/j.1467-789x.2002.00072.x · Cited by 180 · see citing works
Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature
Barrett, E. J., Wang, H., Upchurch, C. T., & Liu, Z. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00186.2011 · Cited by 171 · see citing works
Is Visceral Fat Involved in the Pathogenesis of the Metabolic Syndrome? Human Model
Jensen, M. D. (2006) · Obesity · doi:10.1038/oby.2006.278 · Cited by 169 · see citing works
Insulin resistance and the sympathetic nervous system
Egan, B. M. (2003) · Current Hypertension Reports · doi:10.1007/s11906-003-0028-7 · Cited by 169 · see citing works
Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function
Hall, W. L. (2009) · Nutrition Research Reviews · doi:10.1017/s095442240925846x · Cited by 168 · see citing works
Mima, A., Ohshiro, Y., Kitada, M., Matsumoto, M., Geraldes, P., Li, C., Li, Q., White, G. S., Cahill, C., Rask‐Madsen, C., et al. (2011) · Kidney International · doi:10.1038/ki.2010.526 · Cited by 162 · see citing works
Trence, D., Kelly, J. L., & Hirsch, I. B. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030347 · Cited by 162 · see citing works
Clerk, L. H., Rattigan, S., & Clark, M. G. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1138 · Cited by 159 · see citing works
Insulin resistance and vascular function
Baron, A. (2002) · Journal of Diabetes and its Complications · doi:10.1016/s1056-8727(01)00209-4 · Cited by 159 · see citing works
Self-citationArtwohl, M., Roden, M., Waldhäusl, W. K., Freudenthaler, A., & Baumgartner-Parzer, S. M. (2003) · The FASEB Journal · doi:10.1096/fj.03-0301fje · Cited by 158 · see citing works
Nitric Oxide, Atherosclerosis and the Clinical Relevance of Endothelial Dysfunction
Anderson, T. J. (2003) · Heart Failure Reviews · doi:10.1023/a:1022199021949 · Cited by 157 · see citing works
The impact of reactive oxygen species in the development of cardiometabolic disorders: a review
Akhigbe, R. E., & Ajayi, A. F. (2021) · Lipids in Health and Disease · doi:10.1186/s12944-021-01435-7 · Cited by 154 · see citing works
- Authors
- Steinberg, H. O., Tarshoby, M., Monestel, R., Hook, G., Cronin, J., Johnson, A., Bayazeed, B., & Baron, A. D.
- Affiliations
- Indiana University (US)
- Indiana University – Purdue University Indianapolis (US)
- ORCID
- Tarshoby, M
- Venue
- Journal of Clinical Investigation
- Published
- 1997-09-01
- Volume
- 100
- Issue
- 5
- Pages
- 1230-1239
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508300
- OpenAlex
- W2086785365
- Cited by
- 761
- References
- 16
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 17 · 2023: 20 · 2022: 9 · 2021: 19 · 2020: 29 · 2019: 11 · 2018: 19 · 2017: 20 · 2016: 12 · 2015: 22 · 2014: 17 · 2013: 28 · 2012: 33
- FWCI
- 10.61
- 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 (DK 20452, DK42469)
- National Center for Research Resources (MO1-RR75019)
- 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 Function and Risk Factors
- Keywords
- free fatty acids, endothelial dysfunction, endothelium-dependent vasodilation, insulin resistance, methacholine, sodium nitroprusside, leg blood flow, somatostatin, insulin deficiency, Intralipid, obesity, insulin replacement therapy
- MeSH terms
- Adult, Blood Pressure, Endothelium, Vascular, Fat Emulsions, Intravenous, Fatty Acids, Nonesterified, Female, Humans, Insulin, Leg, Male, Nitroprusside, Somatostatin, Vasodilation, 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
