Endocrine Abstracts

Discovery of novel peptides leads to the elucidation of unknown regulatory systems in the body and to the clinical development of diagnosis and therapeutics for diseases. We have used peptidomics approach to profile a complete set of secretory peptides from cultured human endocrine cells and identified two novel carboxy-terminally amidated peptides, 25-amino acid neuroendocrine regulatory peptide (NERP)-1 and 38-amino acid NERP-2, derived from a neurosecretory protein VGF (JBC 2007). NERPs modulate vasopressin release in both ex vivo and in vivo experiments. Vgf unll mice exhibited dwarfism and hypermetabolic rates, suggesting that VGF or VGF-derived peptides play important roles in energy metabolism. NERP-2 was abundant in the lateral hypothalamus, one of orexigenic centers, and colocalizes with orexigenic neuropeptides, orexins. NERP-2 stimulated orexin release from isolated hypothalamic explants. Central administration of NERP-2 activated orexin neurons to enhance feeding, body temperature, oxygen consumption and locomotor activity (AJP 2010). NERP-2’s activities did not appear in orexin-deficient mice. C-terminal amidation of NERP-2 was essential for its biological activities. NERP-2 was also abundant in the pancreatic islets of humans and rodents and colocalizes extensively with insulin in double immunohistochemistry. NERP-2 enhanced glucose (16.7 mM)-stimulated insulin secretion from MIN6 β cells and isolated islets in a dose-dependent manner. Peripheral administration of NERP-2 significantly elevated plasma insulin in both normal rats and mice and melanocortin 4 receptor knockout mice, an obese diabetic mouse model. Fura-2 calcium imaging showed that NERP-2 elevated cytosolic calcium level in MIN6 β cells. NERP-2 is a novel regulator of food intake and glucose metabolism.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.