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 language | English |
---|---|
Pages (from-to) | 512-517 |
Number of pages | 6 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 428 |
Issue number | 4 |
DOIs | |
State | Published - 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