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Departments of Pharmacology and Clinical Pharmacology (J.K., U.P., U.J., M.K.) and Biostatistics (H.H.), University of Turku, and Hormos Medical Corporation (M.K.K.), FIN-20520 Turku, Finland
Address all correspondence and requests for reprints to: Jaana Kallio, M.D., Ph.D., Department of Pharmacology and Clinical Pharmacology, University of Turku, Itäinen Pitkäkatu 4, FIN-20520 Turku, Finland. E-mail: jaana.kallio{at}utu.fi.
Neuropeptide Y (NPY) is an important neurotransmitter in the central and peripheral nervous systems. It has a regulatory role in cardiovascular and metabolic functions and control of hormone release. The leucine 7 to proline 7 (Leu7Pro) polymorphism in the signal peptide of prepro-NPY is associated with increased blood lipid levels, accelerated atherosclerosis, and diabetic retinopathy. This study elucidated the role of this polymorphism in diurnal cardiovascular, metabolic, and hormonal functions of healthy subjects during rest. The two study groups comprised individuals with different genotype, but they were matched for age and body mass index. Subjects with the Leu7Pro polymorphism had significantly lower plasma NPY and norepinephrine concentrations, lower insulin concentrations, higher glucose concentrations, and lower insulin-glucose ratio in plasma than the controls. Heart rate was significantly higher during daytime in the subjects with Leu7Pro polymorphism. Furthermore, these subjects had significantly lower prolactin concentrations in plasma. Systolic and diastolic blood pressure, serum free fatty acid and plasma leptin, ACTH, cortisol, LH, FSH, TSH, free thyroxin, and melatonin concentrations were similar during the 24-h period, compared with controls. These results show that genetically determined changes in NPY levels lead to widespread consequences in the control of sympathoadrenal, metabolic, and hormonal balance in healthy subjects.
This work was supported by the National Technology Agency of Finland and the funds of Turku University Central Hospital.
Abbreviations: BMI, Body mass index; BP, blood pressure; cortisol, 11ß,17,21-trihydroxypregn-4-ene-3,20-dione; FFA, free fatty acid; fT4, free T4; HR, heart rate; IRMA, immunoradiometric assay; Leu7Pro, leucine 7 to proline 7; NE, norepinephrine; NPY, neuropeptide Y; PRL, prolactin.
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