Intraperitoneal administration of nesfatin-1 stimulates glucagon-like peptide-1 secretion in fasted mice

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