Sage Journals: Discover world-class research

Abstract

Endothelial expression of cell adhesion molecules (CAMs) plays an important role in atherosclerosis. Atherosclerosis is increased in hyperinsulinemic states, but whether insulin per se is proatherogenic remains unclear. To investigate the effects of hyperinsulinemia on CAM expression, plasma levels of ICAM-1, VCAM-1 and E-selectin were measured before and after forearm infusion of insulin in healthy subjects. Insulin administration for 2 h resulted in signifi-cant hyperinsulinemia, whereas no significant change was observed in soluble CAMs (all p > 0.05). Because insulin stimulates endothelial release of both endothelin-1 (ET-1) and nitric oxide (NO), which may modulate the expression of CAMs, we also investigated the response of CAMs to ET-1 receptor blockade, alone and in combination with NO synthesis inhibition. ET-1 receptor blockade during hyperinsulinemia resulted in a vasodilator response, but did not affect soluble CAMs (all p > 0.05). Superimposition of NO inhibition by l-NMMA reversed the vasodilator effect of ET-1 blockade, without affecting soluble CAMs (all p > 0.05). In conclusion, acute hyperinsulinemia, alone or during ET-1 and NO pathway blockade, does not affect soluble CAMs. These results do not support a direct effect of insulin on endothelial cells to affect leukocyte adhesiveness to the vascular wall.

Keywords

cell adhesion molecules endothelin endothelium insulin nitric oxide

References

Price DT , Loscalzo J. Cellular adhesion molecules and atherogenesis. Am J Med 1999; 107: 85-97.

Kriegelstein CF , Granger DN. Adhesion molecules and their role in vascular disease. Am J Hypertens 2001; 14(2): 44S-54S.

Reusch JE. Current concepts in insulin resistance, type 2 diabetes mellitus and the metabolic syndrome. Am J Cardiol 2002; 90: 19G-26G.

Haffner S , Taegtmeyer H. Epidemic of obesity and metabolic syndrome. Circulation 2003; 108: 1541-1545.

Straczkowski M , Lewczuk P , Dzienis-Straczkowska S , Kowalska I , Stepien A , Kinalska I. Elevated soluble intercellular adhesion molecule-1 levels in obesity: relationship to insulin resistance and tumor necrosis factor-alpha system activity. Metabolism 2002; 51: 75-78.

Preston RA , Leodford M , Materson BJ , Memon A , Alonso A. Effects of severe, uncontrolled hypertension on endothelial activation: soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, and von Willebrand factor. JHypertens 2002; 20: 871-877.

Lupattelli G , Marchesi S , Lombardini R et al. Mechanisms of high-density lipoprotein cholesterol effects on endothelial function in hyper-lipidemia. Metabolism 2003; 52: 1191-1195.

Leinonen E , Hurt-Camejo E , Wiklund O , Hulten LM , Hiukka A , Taskinen MR. Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesion molecules in type 2 diabetes. Atherosclerosis 2003; 166: 387-394.

Cardillo C , Nambi SS , Kilcoyne CM et al. Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation 1999; 100: 820-825.

10.

Vicent D , Ilany J , Kondo T et al. The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance. J Clin Invest 2003; 111: 1373-1380.

11.

Ishizuka T , Takamizawa-Matsumoto M , Suzuki K , Kurita A. Endothelin-1 enhances vascular cell adhesion molecule-1 expression in tumor necrosis factor alpha-stimulated vascular endothelial cells. Eur J Pharmacol 1999; 369: 237-245.

12.

Zouki C , Baron C , Fournier A , Filep JG. Endothelin-1 enhances neutrophil adhesion to human coronary artery endothelial cells: role of ET(A) receptors and platelet activating factor. Br J Pharmacol 1999; 127: 969-979.

13.

Laroux FS , Lefer DJ , Kawachi S , et al. Role of nitric oxide in the regulation of acute and chronic inflammation. Antioxid Redox Signal 2000; 2: 391-396.

14.

Ihara M , Noguchi K , Saeki T et al. Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor. Life Sci 1992; 50: 247-255.

15.

Ishikawa K , Ihara M , Noguchi K et al. Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788. Proc Natl Acad Sci USA 1994; 91: 4892-4896.

16.

Rees DD , Palmer RM , Hodson HF , Moncada S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol 1989; 96: 418-424.

17.

Fasching P , Veitl M , Rohac M et al. Elevated concentrations of soluble adhesion molecules and their association with microvascular complications in insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1996; 81: 4313-4317.

18.

Ridker PM , Hennekens CH , Roitman-Johnson B , Stampfer MJ , Allen J. Plasma concentration of soluble intercellular adhesion molecule 1 and risk of future myocardial infarction in apparently healthy men. Lancet 1998; 351: 88-92.

19.

De Mattia G , Bravi MC , Costanzo A et al. Effects of insulin on in vitro vascular cell adhesion molecule-1 expression and in vivo soluble VCAM-1 release. Diabetologia 1999; 42: 1235-1239.

20.

Nagai Y , Takamura T , Nohara E , Yamashita H , Kobayashi K. Serum soluble adhesion molecule concentrations are not regulated by acute hyperinsulinemia in healthy men. Diabet Med 1999; 16: 618-619.

21.

Ferri C , Desideri G , Baldoncini R et al. Early activation of vascular endothelium in nonobese, nondiabetic essential hypertensive patients with multiple metabolic abnormalities. Diabetes 1998; 47: 660-667.

22.

Matsumoto K , Miyake S , Yano M , Ueki Y , Tominaga Y. High serum concentrations of soluble E-selectin in patients with impaired glucose tolerance with hyperinsulinemia. Atherosclerosis 2000; 152: 415-420.

23.

Jilma B , Dallinger S , Hergovich N , Eichler HG , Richter V , Wagner OF. Effects of hyperinsulinemia on plasma levels of circulating adhesion molecules. J Clin Endocrinol Metab 2000; 85: 1748-1751.

24.

Jilma B , Blann A , Pernerstorfer T et al. Regulation of adhesion molecules during human endotoxemia. No acute effects of aspirin. Am J Respir Crit Care Med 1999; 159: 857-863.

25.

Tsutamoto T , Hisanaga T , Wada A et al. Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J Am Coll Cardiol 1998; 31: 391-398.

26.

Aljada A , Saadeh R , Assian E , Ghanim H , Dandona P. Insulin inhibits the expression of intercellular adhesion molecule-1 by human aortic endothelial cells through stimulation of nitric oxide. J Clin Endocrinol Metab 2001; 85: 2572-2575.

27.

Jilma B , Szalay T , Dirnberger E et al. Effects of endothelin-1 on circulating adhesion molecules in man. Eur J Clin Invest 1997; 27: 850-856.

Plasma levels of cell adhesion molecules during hyperinsulinemia and modulation of vasoactive mediators

Abstract

Keywords

References