Abstract
Objectives:
Neuropeptide Y (NPY) plays a central in energy homeostasis and potentially in the development of obesity-related comorbidities, like type II diabetes. As the PreproNPY Leu7Pro polymorphism probably changes the intracellular processing of the synthesized preproNPY peptide, we assessed the hypothesis that PreproNPY Leu7Pro polymorphism is a risk factor for type II diabetes, impaired glucose tolerance and hypertension.
Design:
Blood pressure recordings and oral glucose tolerance test were performed in the hypertensive (n=515) and control cohorts (n=525) of our well-defined Oulu Project Elucidating Risk of Atherosclerosis (OPERA) study. The prevalence of type II diabetes was 9% (n=93). The genotypes, insulin and glucose metabolism indexes and plasma ghrelin of the subjects were determined.
Results:
Pro7 allele frequencies were 5.9, 5.3 and 11.3% in the total cohort, in subjects without and with type II diabetes, respectively. The PreproNPY Pro7 carrier status was a significant risk factor for type II diabetes, and the effect remained significant after adjustment for age, sex, waist circumference and study group (odds ratio=3.02, confidence interval: 1.67–5.44 and P<0.001). Pro7 carriers were more insulin resistant and showed lower ghrelin levels compared to non-carriers.
Conclusions:
The PreproNPY Pro7 allele is associated with an increased risk for type II diabetes. The risk seems to be associated with a higher insulin resistance among Pro7 carriers whereas low ghrelin concentrations in Pro7 carriers are possibly a consequence of high insulin levels.
Sponsorship:
None.
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References
Egan BM (2003). Insulin resistance and the sympathetic nervous system. Curr Hypertens Rep 5, 247–254.
Jaakkola U, Kuusela T, Jartti T, Pesonen U, Koulu M, Vahlberg T et al. (2005). The Leu7Pro polymorphism of preproNPY is associated with decreased insulin secretion, delayed ghrelin suppression, and increased cardiovascular responsiveness to norepinephrine during oral glucose tolerance test. J Clin Endocrinol Metab 90, 3646–3652.
Kallio J, Pesonen U, Jaakkola U, Karvonen MK, Helenius H, Koulu M (2003). Changes in diurnal sympathoadrenal balance and pituitary hormone secretion in subjects with Leu7Pro polymorphism in the prepro-neuropeptide Y. J Clin Endocrinol Metab 88, 3278–3283.
Kallio J, Pesonen U, Kaipio K, Karvonen MK, Jaakkola U, Heinonen OJ et al. (2001). Altered intracellular processing and release of neuropeptide Y due to leucine 7 to proline 7 polymorphism in the signal peptide of preproneuropeptide Y in humans. FASEB J 15, 1242–1244.
Koulu M, Movafagh S, Tuohimaa J, Jaakkola U, Kallio J, Pesonen U et al. (2004). Neuropeptide Y and Y2-receptor are involved in development of diabetic retinopathy and retinal neovascularization. Ann Med 36, 232–240.
Mattevi VS, Zembrzuski VM, Hutz MH (2002). Association analysis of genes involved in the leptin-signaling pathway with obesity in Brazil. Int J Obes Relat Metab Disord 26, 1179–1185.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985). Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412–419.
Niskanen L, Karvonen MK, Valve R, Koulu M, Pesonen U, Mercuri M et al. (2000a). Leucine 7 to proline 7 polymorphism in the neuropeptide Y gene is associated with enhanced carotid atherosclerosis in elderly patients with type 2 diabetes and control subjects. J Clin Endocrinol Metab 85, 2266–2269.
Niskanen L, Voutilainen-Kaunisto R, Terasvirta M, Karvonen MK, Valve R, Pesonen U et al. (2000b). Leucine 7 to proline 7 polymorphism in the neuropeptide Y gene is associated with retinopathy in type 2 diabetes. Exp Clin Endocrinol Diabetes 108, 235–236.
Nordman S, Ding B, Ostenson CG, Karvestedt L, Brismar K, Efendic S et al. (2005). Leu7Pro polymorphism in the neuropeptide Y (NPY) gene is associated with impaired glucose tolerance and type 2 diabetes in Swedish men. Exp Clin Endocrinol Diabetes 113, 282–287.
Pihlajamäki J, Karhapää P, Vauhkonen I, Kekalainen P, Kareinen A, Viitanen L et al. (2003). The Leu7Pro polymorphism of the neuropeptide Y gene regulates free fatty acid metabolism. Metabolism 52, 643–646.
Pöykkö SM, Kellokoski E, Horkko S, Kauma H, Kesaniemi YA, Ukkola O (2003). Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes 52, 2546–2553.
Rantala AO, Kauma H, Lilja M, Savolainen MJ, Reunanen A, Kesäniemi YA (1999). Prevalence of the metabolic syndrome in drug-treated hypertensive patients and control subjects. J Intern Med 245, 163–174.
Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K et al. (2001). Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 50, 227–232.
Williams G, Bing C, Cai XJ, Harrold JA, King PJ, Liu XH (2001). The hypothalamus and the control of energy homeostasis: different circuits, different purposes. Physiol Behav 74, 683–701.
Acknowledgements
This study was supported by the Medical Council of the Academy of Finland and the Finnish Foundation for Cardiovascular Research. We acknowledge the excellent technical assistance of Ms Heidi Häikiö and Ms Saija Kortetjärvi.
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Guarantor: O Ukkola.
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Ukkola, O., Kesäniemi, Y. Leu7Pro polymorphism of PreproNPY associated with an increased risk for type II diabetes in middle-aged subjects. Eur J Clin Nutr 61, 1102–1105 (2007). https://doi.org/10.1038/sj.ejcn.1602621
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DOI: https://doi.org/10.1038/sj.ejcn.1602621
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