Nesfatin-1 Acts As An Inhibitory Factor In Human Gastrointestinal Smooth Muscle Cells In Diabetes Mellitus-Induced Delayed Gastric Emptying

Diabetes mellitus (DM) brings about multiple gastrointestinal complications. Nesfatin-1 is an ingestion regulating peptide which possesses a considerable effect in delaying gastric emptying. We aimed to investigate effects and mechanism of nesfatin-1 application on human gastrointestinal smooth muscle cells (HGSMC). HGSMC were treated with different concentrations of nesfatin-1, and expression of endothelial nitric oxide synthases (eNOS) was confirmed. Besides, HGSMCs were administrated nesfatin-1 along or combination of nesfatin-1 and eNOS inhibitor NG-Nitro L-arginine Methyl Ester (L-NAME). Thereafter, the cell viability, apoptosis, and adhesion were assessed. Western blot analysis was performed to analyze expression of key proteins extracellular regulated protein kinas (ERK) 1/2, p38 mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) on the signaling pathway. The eNOS was significantly upregulated by nesfatin-1 at the optimal concentration of 100 nM (P < 0.05). Nesfatin-1 remarkably suppressed the HGSMC viability and adhesion (P < 0.05) and expedited apoptosis (P < 0.01). Additionally, nesfatin-1 significantly reduced expressions of ERK1/2, p38MAPK and mTOR in HGSMC compared with those in the control group (P < 0.05). However, administration of eNOS inhibitor L-NAME could relieve these effects on HGSMC. Nesfatin-1 inhibited cell viability and adhesion of HGSMC, and promoted cell apoptosis. These effects might be by regulating eNOS-mediated downstream ERK/MAPK/mTOR signaling pathway. It reveals that eNOS inhibitor is praised to be a novel therapeutic strategy and target for DM induced gastrointestinal complications.