Apelin Serum Levels are not Associated with Early Atherosclerosis or Fat Distribution in Young Subjects with Increased Risk for Type 2 Diabetes

Abstract

Apelin is proposed to possess protective cardiovascular properties and may furthermore promote favorable effects on glucose metabolism. First data in humans seem to support this hypothesis. Therefore we aimed to assess the meaning of apelin as an early risk indicator in young subjects prone to atherosclerosis and type 2 diabetes. Furthermore we examined the association of apelin serum levels with insulin sensitivity/resistance and body fat distribution as probably dependent cardiovascular risk factors. We examined 344 individuals (f/m=216/128, mean age 46±1 years) with an increased risk for type 2 diabetes. Apelin-36 serum levels were measured via ELISA. Endothelial dysfunction and intima media thickness (IMT) were assessed using high resolution ultrasound. Visceral adipose tissue (VAT) was measured with an axial T1-weighted fast spin echo technique with a 1.5 T whole-body imager. According to the study population's age, FMD (6.4±0.2%) and IMT (0.56±0.01 mm) were within the expected ranges. Gender or age had no influence on serum apelin levels. When looked at early stages of atherosclerosis, we could not detect a significant correlation between apelin serum levels and FMD or IMT. Blood pressure as well was unaffected by serum apelin levels. Furthermore, neither parameters of insulin sensitivity like insulin sensitivity index (ISI), nor fat distribution like BMI, grade of adiposity, total adipose tissue or VAT were associated with apelin serum levels. We conclude that apelin serum levels do not add further information on the cardiovascular-, or diabetes risk pattern in a diabetes prone population.

adipokine - endothelial dysfunction - intima-media-thickness - insulin resistance - fat distribution

References

• 1 Ashley EA, Powers J, Chen M. et al . The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo.  Cardiovasc Res. 2005;  65 73-82
• 2 Berry MF, Pirolli TJ, Jayasankar V. et al . Apelin has in vivo inotropic effects on normal and failing hearts.  Circulation. 2004;  110 II187-II193
• 3 Bots ML, Hoes AW, Koudstaal PJ. et al . Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study.  Circulation. 1997;  96 1432-1437
• 4 Boucher J, Masri B, Daviaud D. et al . Apelin, a newly identified adipokine up-regulated by insulin and obesity.  Endocrinology. 2005;  146 1764-1771
• 5 Celermajer DS, Sorensen KE, Georgakopoulos D. et al . Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults.  Circulation. 1993;  88 2149-2155
• 6 Chun HJ, Ali ZA, Kojima Y. et al . Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis.  J Clin Invest. 2008;  118 3343-3354
• 7 Dray C, Debard C, Jager J. et al . Apelin and APJ regulation in adipose tissue and skeletal muscle of type 2 diabetic mice and humans.  Am J Physiol Endocrinol Metab. 2010; 
• 8 Dray C, Knauf C, Daviaud D. et al . Apelin stimulates glucose utilization in normal and obese insulin-resistant mice.  Cell Metab. 2008;  8 437-445
• 9 Hashimoto T, Kihara M, Imai N. et al . Requirement of apelin-apelin receptor system for oxidative stress-linked atherosclerosis.  Am J Pathol. 2007;  171 1705-1712
• 10 Ishida J, Hashimoto T, Hashimoto Y. et al . Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo.  J Biol Chem. 2004;  279 26274-26279
• 11 Japp AG, Cruden NL, Amer DA. et al . Vascular effects of apelin in vivo in man.  J Am Coll Cardiol. 2008;  52 908-913
• 12 Li L, Yang G, Li Q. et al . Changes and relations of circulating visfatin, apelin, and resistin levels in normal, impaired glucose tolerance, and type 2 diabetic subjects.  Exp Clin Endocrinol Diabetes. 2006;  114 544-548
• 13 Li Z, Bai Y, Hu J. Reduced apelin levels in stable angina.  Intern Med. 2008;  47 1951-1955
• 14 Machann J, Thamer C, Schnoedt B. et al . Standardized assessment of whole body adipose tissue topography by MRI.  J Magn Reson Imaging. 2005;  21 455-462
• 15 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.  Diabetes Care. 1999;  22 1462-1470
• 16 O’Leary DH, Polak JF, Kronmal RA. et al . Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group.  N Engl J Med. 1999;  340 14-22
• 17 Rittig K, Peter A, Baltz KM. et al . The CCR2 promoter polymorphism T-960A, but not the serum MCP-1 level, is associated with endothelial function in prediabetic individuals.  Atherosclerosis. 2008;  198 338-346
• 18 Schafer S, Kantartzis K, Machann J. et al . Lifestyle intervention in individuals with normal versus impaired glucose tolerance.  Eur J Clin Invest. 2007;  37 535-543
• 19 Soriguer F, Garrido-Sanchez L, Garcia-Serrano S. et al . Apelin Levels Are Increased in Morbidly Obese Subjects with Type 2 Diabetes Mellitus.  Obes Surg. 2009; 
• 20 Tatemoto K, Takayama K, Zou MX. et al . The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism.  Regul Pept. 2001;  99 87-92
• 21 Wendelhag I, Gustavsson T, Suurkula M. et al . Ultrasound measurement of wall thickness in the carotid artery: fundamental principles and description of a computerized analysing system.  Clin Physiol. 1991;  11 565-577
• 22 Yue P, Jin H, Aillaud-Manzanera M. et al . Apelin is necessary for the maintenance of insulin sensitivity.  Am J Physiol Endocrinol Metab. 2009; 
• 23 Zhong JC, Yu XY, Huang Y. et al . Apelin modulates aortic vascular tone via endothelial nitric oxide synthase phosphorylation pathway in diabetic mice.  Cardiovasc Res. 2007;  74 388-395

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