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.
BACKGROUND
Neuropeptide Y (NPY) plays a role in angiogenesis, cardiovascular regulation, and hormone secretion. The leucine7 to proline7 (Leu7Pro) polymorphism of preproNPY is associated with vascular diseases and has an impact on hormone levels in healthy subjects.


OBJECTIVE
The current study investigated the role of the Leu7Pro polymorphism in metabolic and cardiovascular autonomic regulation.


METHODS
A 5-h oral glucose tolerance test was performed on 27 healthy volunteers representing two preproNPY genotypes (Leu7/Pro7 and Leu7/Leu7) matched for age, sex, body mass index and physical activity.


METHODS
Simultaneously we performed cardiovascular autonomic function tests and plasma measurements of sympathetic transmitters, glucose, insulin, and ghrelin.


RESULTS
The subjects with Leu7/Pro7 genotype had decreased plasma NPY, norepinephrine (NE), and insulin concentrations and insulin to glucose ratios. The suppression of ghrelin concentrations after glucose ingestion was delayed in these subjects. They also had increased heart rate variability indices and baroreflex sensitivity. However, they displayed significant negative association of NE concentration with variability of low-frequency R-R-intervals and with baroreflex sensitivity.


CONCLUSIONS
The Leu7Pro polymorphism of preproNPY is related to decreased level of basal sympathetic activity, decreased insulin secretion, and delayed ghrelin suppression during oral glucose tolerance test. The increased responsiveness of autonomic functions to NE associated with the polymorphism may be connected to increased cardiovascular vulnerability.
Jaakkola
Ulriikka
U
Department of Pharmacology and Clinical Pharmacology, University of Turku, Itäinen Pitkäkatu 4, FI-20520 Turku, Finland. jaana.kallio@utu.fi
Kuusela
Tom
T
Jartti
Tuomas
T
Pesonen
Ullamari
U
Koulu
Markku
M
Vahlberg
Tero
T
Kallio
Jaana
J
D000328:Adult; D019943:Amino Acid Substitution; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure; D005260:Female; D005838:Genotype; D054439:Ghrelin; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007930:Leucine; D008297:Male; D020125:Mutation, Missense; D009478:Neuropeptide Y / Q000235:genetics*; D008771:Nordefrin / Q000494:pharmacology*; D036361:Peptide Hormones / Q000097:blood*; D011392:Proline; D011498:Protein Precursors / Q000235:genetics*
D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D009478:Neuropeptide Y; D036361:Peptide Hormones; D011498:Protein Precursors; C042084:preproneuropeptide Y; D011392:Proline; D007930:Leucine; D008771:Nordefrin