Neuropeptide Y promotes β-cell replication via extracellular signal-regulated kinase activation

• Published in: Biochemical and biophysical research communications Vol. 314; no. 3; pp. 773 - 780
• Main Authors: Cho, Y.R, Kim, C.W
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.02.2004
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; Arginine - analogs & derivatives; Arginine - pharmacology; BIBP3226; BIM-1; Bromodeoxyuridine - immunology; Bromodeoxyuridine - metabolism; Cell Division - drug effects; Cell Division - physiology; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; Extracellular signal-regulated kinase; Fluorescent Antibody Technique - methods; In Situ Nick-End Labeling - methods; Insulin; Insulin - metabolism; Insulin Antagonists - pharmacology; Insulin Secretion; Islet; Islets of Langerhans - cytology; Islets of Langerhans - drug effects; Islets of Langerhans - enzymology; Male; Mice; Mice, Inbred ICR; Microscopy, Confocal; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Neuropeptide Y; Neuropeptide Y - pharmacology; PD98059; Phosphoinositide 3-kinase; Protein kinase C; Receptors, Neuropeptide Y - antagonists & inhibitors; Receptors, Neuropeptide Y - genetics; Receptors, Neuropeptide Y - metabolism; Time Factors; Wortmannin; Neuropeptide Y; Phosphoinositide 3-kinase; Protein kinase C; Wortmannin; Extracellular signal-regulated kinase; PD98059; BIBP3226; Islet; Insulin; BIM-1
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2003.12.170

Aims/hypothesis. 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. β-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. Conclusion/interpretation. Our data suggest that NPY promotes β-cell replication via extracellular signal-regulated kinase activation and inhibits glucose-stimulated insulin secretion.