Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance - PubMed (original) (raw)
Comparative Study
. 1996 Jun 1;97(11):2601-10.
doi: 10.1172/JCI118709.
Affiliations
- PMID: 8647954
- PMCID: PMC507347
- DOI: 10.1172/JCI118709
Comparative Study
Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance
H O Steinberg et al. J Clin Invest. 1996.
Abstract
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.
Comment in
- Insulin resistance in the vasculature.
Mather KJ, Steinberg HO, Baron AD. Mather KJ, et al. J Clin Invest. 2013 Mar;123(3):1003-4. doi: 10.1172/JCI67166. Epub 2013 Mar 1. J Clin Invest. 2013. PMID: 23454764 Free PMC article.
Similar articles
- Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release.
Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Steinberg HO, et al. J Clin Invest. 1994 Sep;94(3):1172-9. doi: 10.1172/JCI117433. J Clin Invest. 1994. PMID: 8083357 Free PMC article. - Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation.
Steinberg HO, Tarshoby M, Monestel R, Hook G, Cronin J, Johnson A, Bayazeed B, Baron AD. Steinberg HO, et al. J Clin Invest. 1997 Sep 1;100(5):1230-9. doi: 10.1172/JCI119636. J Clin Invest. 1997. PMID: 9276741 Free PMC article. - Endothelial dysfunction is associated with cholesterol levels in the high normal range in humans.
Steinberg HO, Bayazeed B, Hook G, Johnson A, Cronin J, Baron AD. Steinberg HO, et al. Circulation. 1997 Nov 18;96(10):3287-93. doi: 10.1161/01.cir.96.10.3287. Circulation. 1997. PMID: 9396418 - Insulin resistance and vascular function.
Baron AD. Baron AD. J Diabetes Complications. 2002 Jan-Feb;16(1):92-102. doi: 10.1016/s1056-8727(01)00209-4. J Diabetes Complications. 2002. PMID: 11872375 Review. - Vascular function, insulin resistance and fatty acids.
Steinberg HO, Baron AD. Steinberg HO, et al. Diabetologia. 2002 May;45(5):623-34. doi: 10.1007/s00125-002-0800-2. Epub 2002 Apr 4. Diabetologia. 2002. PMID: 12107742 Review.
Cited by
- Mechanisms of endothelial dysfunction in obesity-associated hypertension.
Lobato NS, Filgueira FP, Akamine EH, Tostes RC, Carvalho MH, Fortes ZB. Lobato NS, et al. Braz J Med Biol Res. 2012 May;45(5):392-400. doi: 10.1590/s0100-879x2012007500058. Epub 2012 Apr 12. Braz J Med Biol Res. 2012. PMID: 22488221 Free PMC article. - Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells.
Kim HS, Ren G, Kim T, Bhatnagar S, Yang Q, Bahk YY, Kim JA. Kim HS, et al. Sci Rep. 2020 Aug 11;10(1):13523. doi: 10.1038/s41598-020-70347-w. Sci Rep. 2020. PMID: 32782332 Free PMC article. - WNT5A-JNK regulation of vascular insulin resistance in human obesity.
Farb MG, Karki S, Park SY, Saggese SM, Carmine B, Hess DT, Apovian C, Fetterman JL, Bretón-Romero R, Hamburg NM, Fuster JJ, Zuriaga MA, Walsh K, Gokce N. Farb MG, et al. Vasc Med. 2016 Dec;21(6):489-496. doi: 10.1177/1358863X16666693. Epub 2016 Sep 28. Vasc Med. 2016. PMID: 27688298 Free PMC article. - Altered neurovascular control of the resting circulation in human metabolic syndrome.
Limberg JK, Morgan BJ, Sebranek JJ, Proctor LT, Walker BJ, Eldridge MW, Schrage WG. Limberg JK, et al. J Physiol. 2012 Dec 1;590(23):6109-19. doi: 10.1113/jphysiol.2012.239780. Epub 2012 Oct 1. J Physiol. 2012. PMID: 23027821 Free PMC article. Clinical Trial. - Relaxin treatment reverses insulin resistance in mice fed a high-fat diet.
Bonner JS, Lantier L, Hocking KM, Kang L, Owolabi M, James FD, Bracy DP, Brophy CM, Wasserman DH. Bonner JS, et al. Diabetes. 2013 Sep;62(9):3251-60. doi: 10.2337/db13-0033. Epub 2013 Jun 25. Diabetes. 2013. PMID: 23801576 Free PMC article.
References
- Clin Chem. 1972 Jun;18(6):499-502 - PubMed
- Am J Physiol. 1994 May;266(5 Pt 2):H2146-51 - PubMed
- Ann Intern Med. 1985 Dec;103(6 ( Pt 2)):1047-9 - PubMed
- N Engl J Med. 1987 Aug 6;317(6):350-7 - PubMed
- Br J Pharmacol. 1987 Nov;92(3):639-46 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous