Neuropeptide Y promotes beta-cell replication via extracellular signal-regulated kinase activation.
OBJECTIVE
Previous studies have shown that neuropeptide Y (NPY) gene expression and release are increased in hyperphagic ob/ob mice and diabetic rats. Therefore, we hypothesized that orexigenic agent, NPY, has the effect on the obesity and diabetes. To elucidate the relationship, we have studied the regulatory role of NPY on islet cells.


METHODS
Isolated islets were incubated with NPY or NPY Y1 receptor specific antagonist, BIBP3226. Proliferation, apoptosis, and Y1 receptor expression were identified by immunohistochemistry. We studied that ERK1/2 mediates the NPY pathway with PD98059 (MAP kinase inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), and BIM-1 (protein kinase C inhibitor). After NPY-treated islets were exposed to high glucose, insulin levels were detected.


RESULTS
beta-Cell replication was enhanced in a dose-dependent manner, but without any changes on the other cells in islet. NPY Y1 receptors were expressed on islet and NPY induced phosphorylation of ERK1/2 rapidly and transiently. PD98059 (MAPK kinase inhibitor) and BIM-1 (protein kinase C inhibitor) inhibited activation of ERK1/2 by NPY, but wortmannin (phosphatidylinositol 3-kinase inhibitor) did not. Exposure of NPY-treated islets to high glucose showed the decreasing trend of insulin secretion.


CONCLUSIONS
Our data suggest that NPY promotes beta-cell replication via extracellular signal-regulated kinase activation and inhibits glucose-stimulated insulin secretion.
Cho
Y R
YR
Graduate School of Life Sciences and Biotechnology, Korea University, 136-701, Seoul, Republic of Korea.
Kim
C W
CW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007328:Insulin / Q000378:metabolism; D007329:Insulin Antagonists / Q000494:pharmacology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
C092926:BIBP 3226; D004791:Enzyme Inhibitors; D007328:Insulin; D007329:Insulin Antagonists; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D001120:Arginine; D020928:Mitogen-Activated Protein Kinases; D001973:Bromodeoxyuridine