Stephen E Flaherty, Olivier Bezy, Wei Zheng, Dong Yan, Xiangping Li, Srinath Jagarlapudi, Bina Albuquerque, Ryan M Esquejo, Matthew Peloquin, Meriem Semache, Arturo Mancini, Liya Kang, Doreen Drujan, Susanne B Breitkopf, John D Griffin, Pierre M Jean Beltran, Liang Xue, John Stansfield, Evanthia Pashos, Quazi Shakey, Christian Pehmøller, Mara Monetti, Morris J Birnbaum, Jean-Philippe Fortin, Zhidan Wu
Urocortin 2 (UCN2) acts as a ligand for the G protein-coupled receptor corticotropin-releasing hormone receptor 2 (CRHR2). UCN2 has been reported to improve or worsen insulin sensitivity and glucose tolerance in vivo. Here we show that acute dosing of UCN2 induces systemic insulin resistance in male mice and skeletal muscle. Inversely, chronic elevation of UCN2 by injection with adenovirus encoding UCN2 resolves metabolic complications, improving glucose tolerance. CRHR2 recruits Gs in response to low concentrations of UCN2, as well as Gi and β-Arrestin at high concentrations of UCN2...
July 4, 2023: Nature Communications