Submitted on November 20, 2003
Accepted on May 30, 2004
Selective Activation of Central NPY Y1 vs. Y5 Receptor Elicits Hyperinsulinemia via Distinct Mechanisms
Jun Gao1, Lorraine Ghibaudi1, and Joyce J. Hwa1*
1 Department of Cardiovascular/Metabolic Diseases, Schering-Plough Research Institute, Kenilworth, NJ, USA
* To whom correspondence should be addressed. E-mail: joyce.hwa{at}spcorp.com.
Central administration of neuropeptide Y (NPY) stimulates hyperphagia and
hyperinsulinemia. Recent evidence has suggested that the Y1 and Y5 receptor subtypes may
both mediate NPY-stimulated feeding. The present study attempts to further characterize the
role of central NPY receptor subtypes involved in hyperinsulinemia. NPY and peptide analogs
of NPY that selectively activated the NPY Y1 or Y5 receptor subtype induced feeding and
hyperinsulinemia in satiated LE rats, while NPY analogs that selectively activated the NPY Y2
or Y4 receptor subtype did not. To determine if NPY-induced hyperinsulinemia is secondary to
its hyperphagic effect, we compared the plasma insulin levels in the presence and absence of
food after a one-minute central infusion of NPY and its analogs at 15, 60 and 120 min post
infusion. Our data suggest that selective activation of central NPY Y1 receptor subtype induced
hyperinsulinemia independent of food ingestion, whereas the NPY Y5 receptor-induced
hyperinsulinemia was dependent on food ingestion. Central administration of the selective Y1
receptor agonist, D-Arg25 NPY, eventually decreased plasma glucose levels 2h post infusion in
LE rats.
