Neuroendocrine regulatory peptide-2 stimulates glucose-induced insulin secretion in vivo and in vitro

Abu Saleh Md Moin, Hideki Yamaguchi, Marie Rhee, Ji Wom Kim, Koji Toshinai, T. M.Zaved Waise, Farhana Naznin, Takashi Matsuo, Kazuki Sasaki, Naoto Minamino, Kun Ho Yoon, Masamitsu Nakazato

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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 10-7M, 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.

Original languageEnglish
Pages (from-to)512-517
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume428
Issue number4
DOIs
StatePublished - 30 Nov 2012

Bibliographical note

Funding Information:
We thank R. Matsuura for expert technical assistance. This work was supported in part by JSPS KAKENHI (No. 23591358 ) to H.Y.; and MEXT KAKENHI (No. 22126009 ), JSPS KAKENHI (No. 22390190 ), grants from Takeda Science Foundation , and Strategic International Research Cooperative Program, Japan Science and Technology Agency (JST) to M.N.

Keywords

  • Ca
  • DAB
  • GSIS
  • Insulin secretion
  • NERP
  • NERP-2
  • VGF

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