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

Biochem Biophys Res Commun. 2012 Nov 30;428(4):512-7. doi: 10.1016/j.bbrc.2012.10.073. Epub 2012 Oct 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / pharmacology
  • Nerve Tissue Proteins / physiology*
  • Neuropeptides / genetics
  • Neuropeptides / pharmacology
  • Neuropeptides / physiology*
  • Rats
  • Rats, Wistar


  • Insulin
  • Nerve Tissue Proteins
  • Neuropeptides
  • Vgf protein, mouse
  • neuroendocrine regulatory peptide-2, mouse
  • Glucose