Nes-1

This study investigates the role of nesfatin-1, a peptide derived from nucleobindin 2, in glucose homeostasis and insulin sensitivity through central signaling mechanisms. By infusing nesfatin-1 into the third cerebral ventricle of high-fat diet (HFD)-fed rats, the researchers assessed its impact on glucose metabolism using euglycemic-hyperinsulinemic clamping. The infusion of nesfatin-1 significantly reduced hepatic glucose production (HGP) and promoted muscle glucose uptake. These effects were accompanied by a decrease in the expression and activity of the gluconeogenic enzyme PEPCK in both standard and HFD-fed rats. Additionally, nesfatin-1 infusion activated the insulin receptor (InsR)/insulin receptor substrate-1 (IRS-1)/AMP-activated protein kinase (AMPK)/Akt kinase (Akt)/target of rapamycin complex (TORC) 2 signaling pathway and increased Fos immunoreactivity in hypothalamic nuclei involved in glucose regulation. These findings reveal a novel mechanism through which hypothalamic nesfatin-1 modulates glucose homeostasis by enhancing insulin sensitivity and reducing gluconeogenesis, suggesting its potential as a therapeutic target for metabolic disorders.