This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aljada, A. Articles by Dandona, P. Search for Related Content PubMed PubMed Citation Articles by Aljada, A. Articles by Dandona, P.

Insulin Inhibits the Expression of Intercellular Adhesion Molecule-1 by Human Aortic Endothelial Cells through Stimulation of Nitric Oxide¹

Division of Endocrinology, Diabetes, and Metabolism, State University of New York, Buffalo, New York 14209; and Kaleida Health, Buffalo, New York 14209

Address all correspondence and requests for reprints to: Paresh Dandona, M.D., Ph.D., Diabetes-Endocrinology Center of Western New York, State University of New York, 3 Gates Circle, Buffalo, New York 14209. E-mail: pdandona{at}mfhs.edu

Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelial and other cell types and participates in inflammation and atherosclerosis. It serves as a ligand for leukocyte function-associated antigen-1 on leukocytes and is partially responsible for the adhesion of lymphocytes, granulocytes, and monocytes to cytokine-stimulated endothelial cells and the subsequent transendothelial migration. Its expression on endothelial cells is increased in inflammation and atherosclerosis. As it has been suggested that insulin and hyperinsulinemia may have a role in atherogenesis, we have now investigated whether insulin has an effect on the expression of ICAM-1 on human aortic endothelial cells (HAEC). HAEC were prepared from human aortas by collagenase digestion and were grown in culture. Insulin (100 and 1000 µU/mL) caused a decrease in the expression of ICAM-1 (messenger ribonucleic acid and protein) by these cells in a dose-dependent manner after incubation for 2 days. This decrease was associated with a concomitant increase in endothelial nitric oxide synthase (NOS) expression also induced by insulin. To examine whether the insulin-induced inhibition of ICAM-1 was mediated by nitric oxide (NO) from increased endothelial NOS, HAEC were treated with N-nitro-L-arginine, a NOS inhibitor. N-Nitro-L-arginine inhibited the insulin-induced decrease in ICAM-1 expression in HAEC at the messenger ribonucleic acid and protein levels. Thus, the inhibitory effect of insulin on ICAM-1 expression is mediated by NO. We conclude that insulin reduces the expression of the proinflammatory adhesion molecule ICAM-1 through an increase in the expression of NOS and NO generation and that insulin may have a potential antiinflammatory and antiatherosclerotic effect rather than a proatherosclerotic effect.

This article has been cited by other articles:

				M. T. McCormick, K. W. Muir, C. S. Gray, and M. R. Walters Management of Hyperglycemia in Acute Stroke: How, When, and for Whom? Stroke, July 1, 2008; 39(7): 2177 - 2185. [Full Text] [PDF]

				S. Dickinson, D. P Hancock, P. Petocz, A. Ceriello, and J. Brand-Miller High-glycemic index carbohydrate increases nuclear factor-{kappa}B activation in mononuclear cells of young, lean healthy subjects Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1188 - 1193. [Abstract] [Full Text] [PDF]

				S. Walrand, C. Guillet, Y. Boirie, and M.-P. Vasson Insulin Differentially Regulates Monocyte and Polymorphonuclear Neutrophil Functions in Healthy Young and Elderly Humans J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2738 - 2748. [Abstract] [Full Text] [PDF]

				R. Garg, A. Chaudhuri, F. Munschauer, and P. Dandona Hyperglycemia, Insulin, and Acute Ischemic Stroke: A Mechanistic Justification for a Trial of Insulin Infusion Therapy Stroke, January 1, 2006; 37(1): 267 - 273. [Abstract] [Full Text] [PDF]

				M. Wehling-Henricks, M. C. Jordan, K. P. Roos, B. Deng, and J. G. Tidball Cardiomyopathy in dystrophin-deficient hearts is prevented by expression of a neuronal nitric oxide synthase transgene in the myocardium Hum. Mol. Genet., July 15, 2005; 14(14): 1921 - 1933. [Abstract] [Full Text] [PDF]

				T. J. Stalker, Y. Gong, and R. Scalia The Calcium-Dependent Protease Calpain Causes Endothelial Dysfunction in Type 2 Diabetes Diabetes, April 1, 2005; 54(4): 1132 - 1140. [Abstract] [Full Text] [PDF]

				M. O. Goodarzi, K. D. Taylor, X. Guo, M. J. Quinones, J. Cui, X. Li, T. Hang, H. Yang, E. Holmes, W. A. Hsueh, et al. Variation in the Gene for Muscle-Specific AMP Deaminase Is Associated With Insulin Clearance, a Highly Heritable Trait Diabetes, April 1, 2005; 54(4): 1222 - 1227. [Abstract] [Full Text] [PDF]

				S. R. Kashyap, L. J. Roman, J. Lamont, B. S. S. Masters, M. Bajaj, S. Suraamornkul, R. Belfort, R. Berria, D. L. Kellogg Jr., Y. Liu, et al. Insulin Resistance Is Associated with Impaired Nitric Oxide Synthase Activity in Skeletal Muscle of Type 2 Diabetic Subjects J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1100 - 1105. [Abstract] [Full Text] [PDF]

				J. G. Tidball Inflammatory processes in muscle injury and repair Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R345 - R353. [Abstract] [Full Text] [PDF]

				K. M. Choi, K. W. Lee, S. G. Kim, N. H. Kim, C. G. Park, H. S. Seo, D. J. Oh, D. S. Choi, and S. H. Baik Inflammation, Insulin Resistance, and Glucose Intolerance in Acute Myocardial Infarction Patients without a Previous Diagnosis of Diabetes Mellitus J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 175 - 180. [Abstract] [Full Text] [PDF]

				A. Aljada, P. Mohanty, H. Ghanim, T. Abdo, D. Tripathy, A. Chaudhuri, and P. Dandona Increase in intranuclear nuclear factor {kappa}B and decrease in inhibitor {kappa}B in mononuclear cells after a mixed meal: evidence for a proinflammatory effect Am. J. Clinical Nutrition, April 1, 2004; 79(4): 682 - 690. [Abstract] [Full Text] [PDF]

				R. Rossi, G. Origliani, and M. G. Modena Transdermal 17-{beta}-Estradiol and Risk of Developing Type 2 Diabetes in a Population of Healthy, Nonobese Postmenopausal Women Diabetes Care, March 1, 2004; 27(3): 645 - 649. [Abstract] [Full Text] [PDF]

				S. K. Andersen, J. Gjedsted, C. Christiansen, and E. Tonnesen The roles of insulin and hyperglycemia in sepsis pathogenesis J. Leukoc. Biol., March 1, 2004; 75(3): 413 - 421. [Abstract] [Full Text] [PDF]

				S. Clement, S. S. Braithwaite, M. F. Magee, A. Ahmann, E. P. Smith, R. G. Schafer, and I. B. Hirsch Management of Diabetes and Hyperglycemia in Hospitals Diabetes Care, February 1, 2004; 27(2): 553 - 591. [Full Text] [PDF]

				P. Dandona, A. Aljada, P. Mohanty, H. Ghanim, A. Bandyopadhyay, and A. Chaudhuri Insulin Suppresses Plasma Concentration of Vascular Endothelial Growth Factor and Matrix Metalloproteinase-9 Diabetes Care, December 1, 2003; 26(12): 3310 - 3314. [Abstract] [Full Text] [PDF]

				J. S. Steingrub, P. E. Marik, and G. P. Zaloga Steroids and Drotrecogin Alfa (Activated) for Severe Sepsis Chest, November 1, 2003; 124(5): 2033 - 2034. [Full Text] [PDF]

				P. Dandona, A. Aljada, A. Chaudhuri, and A. Bandyopadhyay The Potential Influence of Inflammation and Insulin Resistance on the Pathogenesis and Treatment of Atherosclerosis-Related Complications in Type 2 Diabetes J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2422 - 2429. [Full Text] [PDF]

				P. Dandona, A. Aljada, and A. Bandyopadhyay The Potential Therapeutic Role of Insulin in Acute Myocardial Infarction in Patients Admitted to Intensive Care and in Those With Unspecified Hyperglycemia Diabetes Care, February 1, 2003; 26(2): 516 - 519. [Full Text] [PDF]

				Z. He, C. Rask-Madsen, and G.L. King Mechanisms of cardiovascular complications in diabetes and potential new pharmacological therapies Eur. Heart J. Suppl., January 1, 2003; 5(suppl_B): B51 - B57. [Abstract] [PDF]

				M. Federici, R. Menghini, A. Mauriello, M. L. Hribal, F. Ferrelli, D. Lauro, P. Sbraccia, L. G. Spagnoli, G. Sesti, and R. Lauro Insulin-Dependent Activation of Endothelial Nitric Oxide Synthase Is Impaired by O-Linked Glycosylation Modification of Signaling Proteins in Human Coronary Endothelial Cells Circulation, July 23, 2002; 106(4): 466 - 472. [Abstract] [Full Text] [PDF]

				J. E. Da Silva-Santos, M. C. Santos-Silva, F. d. Q. Cunha, and J. Assreuy The Role of ATP-Sensitive Potassium Channels in Neutrophil Migration and Plasma Exudation J. Pharmacol. Exp. Ther., March 1, 2002; 300(3): 946 - 951. [Abstract] [Full Text] [PDF]

				B. M. Matata and M. Galinanes Effect of Diabetes on Nitric Oxide Metabolism During Cardiac Surgery Diabetes, November 1, 2001; 50(11): 2603 - 2610. [Abstract] [Full Text] [PDF]

				A. Aljada, R. Garg, H. Ghanim, P. Mohanty, W. Hamouda, E. Assian, and P. Dandona Nuclear Factor-{{kappa}}B Suppressive and Inhibitor-{{kappa}}B Stimulatory Effects of Troglitazone in Obese Patients with Type 2 Diabetes: Evidence of an Antiinflammatory Action? J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3250 - 3256. [Abstract] [Full Text] [PDF]

				P. Dandona, A. Aljada, P. Mohanty, H. Ghanim, W. Hamouda, E. Assian, and S. Ahmad Insulin Inhibits Intranuclear Nuclear Factor {{kappa}}B and Stimulates I{{kappa}}B in Mononuclear Cells in Obese Subjects: Evidence for an Anti-inflammatory Effect? J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3257 - 3265. [Abstract] [Full Text] [PDF]

				M. Montagnani, I. Golovchenko, I. Kim, G. Y. Koh, M. L. Goalstone, A. N. Mundhekar, M. Johansen, D. F. Kucik, M. J. Quon, and B. Draznin Inhibition of Phosphatidylinositol 3-Kinase Enhances Mitogenic Actions of Insulin in Endothelial Cells J. Biol. Chem., January 11, 2002; 277(3): 1794 - 1799. [Abstract] [Full Text] [PDF]