Inhibition of neuraminidase-1 sialidase activity by interfering peptides impairs insulin receptor activity in vitro and glucose homeostasis in vivo

In this study, we investigated the effects of these peptides on IR activation in vitro and in vivo. Using cellular overexpression and endogenous expression models of NEU-1 and IR (COS-7 and HepG2 cells respectively), we have shown that interfering peptides inhibit NEU-1 dimerization and sialidase activity which results in a reduction of IR phosphorylation. These results demonstrated that NEU-1 positively regulates IR phosphorylation and activation in our conditions. In vivo, biodistribution study showed that interfering peptides are well distributed in mice. Treatment of C57Bl/6 mice during eight weeks with interfering peptides induces a hyperglycemic effect in our experimental conditions. Altogether, we report here that inhibition of NEU-1 sialidase activity by interfering peptides decreases IR activity in vitro and glucose homeostasis in vivo.PMID:38663826 | DOI:10.1016/j.jbc.2024.107316

Source: Atherosclerosis - April 25, 2024 Category: Cardiology Authors: Kevin Toussaint Aline Appert-Collin Laetitia Vanalderwiert Camille Bour Christine Terryn Caroline Spenl é Micha ël Van Der Heyden Mathilde Roumieux Pascal Maurice B éatrice Romier-Crouzet Herv é Sartelet Laurent Duca S ébastien Blaise Amar Bennasroun Source Type: research