Intraperitoneal administration of nesfatin­1 stimulates glucagon­like peptide­1 secretion in fasted mice.

Increasing endogenous secretion of glucagon­like peptide (GLP)­1 is considered a promising therapeutic approach for type 2 diabetes because decreased GLP­1 plasma concentrations have been observed in patients with this condition. Nesfatin­1, which is a central and peripheral anorexigenic peptide, has been reported to release GLP­1 from enteroendocrine STC­1 cells, although whether nesfatin­1 stimulates GLP­1 secretion in vivo remains to be elucidated. Previous studies have indicated that nesfatin­1 has glucose­lowering and insulinotropic effects in mice and rats; however, the in vivo mechanism remains unclear. The present study aimed to investigate whether peripheral administration of nesfatin­1 increased blood concentrations of GLP­1 and insulin in food­deprived mice. Nesfatin­1 was administered intraperitoneally to 18­h fasted mice. Plasma GLP­1 and insulin concentrations in the mice administered 2.5 µmol/kg nesfatin­1 were higher than those in saline­treated mice. Blood glucose concentrations in mice treated with 1.25 and 2.5 µmol/kg nesfatin­1 were lower than those in saline­treated mice. The mRNA expression of preproglucagon in mouse ilea after treatment with 1.25 µmol/kg nesfatin­1 was higher than that in saline­treated mice. The administration of 1.25 µmol/kg nesfatin­1 raised GLP­1 concentrations at 30 and 60 min and insulin concentrations at 30 and 60 min after injection. Furthermore, the higher level of nesfatin­1­induced insulin was diminished by pre­administration of anti­GLP­1 antiserum. Intraperitoneally administered nesfatin­1 increased insulin concentrations by accelerating GLP­1 secretion. The results are the first in vivo demonstration of promotion of GLP­1 secretion by nesfatin­1 in the mouse, suggesting the developmental potential of nesfatin­1 for GLP­1 release.