title: Neuroendocrine regulatory peptide-2 stimulates glucose-induced insulin secretion in vivo and in vitro.
abstract: Neuroendocrine regulatory peptide (NERP)-2, recently identified as a bioactive peptide involved in vasopressin secretion and feeding regulation in the central nervous system, is abundantly expressed in endocrine cells in peripheral tissues. To explore the physiological roles of NERP-2 in the pancreas, we examined its effects on insulin secretion. NERP-2 increased glucose-stimulated insulin secretion (GSIS) in a dose-dependent manner, with a lowest effective dose of 10(-7) M, from the pancreatic β-cell line MIN6 and isolated mouse pancreatic islets. NERP-2 did not affect insulin secretion under the low-glucose conditions. Neither NERP-1 nor NERP-2-Gly (nonamidated NERP-2) stimulated insulin secretion. NERP-2 significantly augmented GSIS after intravenous administration to anesthetized rats or intraperitoneal injection to conscious mice. We detected NERP-2 in pancreatic islets, where it co-localized extensively with insulin. Calcium-imaging analysis demonstrated that NERP-2 increased the calcium influx in MIN6 cells. These findings reveal that NERP-2 regulates GSIS by elevating intracellular calcium concentrations.
authors.affiliation: Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Abu Saleh Md
authors.initials: AS
authors.lastname: Moin
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Marie
authors.initials: M
authors.lastname: Rhee
authors.forename: Ji-Wom
authors.initials: JW
authors.lastname: Kim
authors.forename: Koji
authors.initials: K
authors.lastname: Toshinai
authors.forename: T M Zaved
authors.initials: TM
authors.lastname: Waise
authors.forename: Farhana
authors.initials: F
authors.lastname: Naznin
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuo
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sasaki
authors.forename: Naoto
authors.initials: N
authors.lastname: Minamino
authors.forename: Kun-Ho
authors.initials: KH
authors.lastname: Yoon
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C512697:Vgf protein, mouse; C579141:neuroendocrine regulatory peptide-2, mouse; D005947:Glucose