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2020-08-15 - Article/Dans un journal avec peer-review - Anglais - 22 page(s)

Crombez Deborah, Delcambre Sébastien, Nonclercq Denis , Vander Elst Luce , Laurent Sophie , Cnop Miriam, Muller Robert , Burtea Carmen , "Modulation of Adiponectin Receptors AdipoR1 and AdipoR2 by Phage Display-Derived Peptides in in vitro and in vivo Models" in Journal of Drug Targeting, 28, 7-8, 831-851

  • Edition : Taylor & Francis (United Kingdom)
  • Codes CREF : Histologie (DI3212), Sciences biomédicales (DI3200), Endocrinologie (DI3322), Biochimie pharmaceutique (DI3491), Biologie moléculaire (DI3111), Diabétologie (DI3373), Chimie organique (DI1313), Biologie cellulaire (DI311D)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108), Histologie (M118)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
  • Centres UMONS : Centre de Recherche en Microscopie et Imagerie Médicale (CMMI)
Texte intégral :

Abstract(s) :

(Anglais) Type 2 diabetes (T2D) is often linked to metabolic syndrome, which assembles various risk factors related to obesity. Plasma levels of adiponectin are decreased in T2D and obese subjects. Aiming to develop a peptide able to bind adiponectin receptors and modulate their signalling pathways, a 12-amino acid sequence homologous in AdipoR1/R2 has been targeted by phage display with a linear 12-mer peptide library. The selected peptide P17 recognizes AdipoR1/R2 expressed by skeletal muscle, liver and pancreatic islets. In HepaRG and C2C12 cells, P17 induced the activation of AMPK (AMPKα-pT172) and the expression of succinate dehydrogenase and glucokinase; no cytotoxic effects were observed on HepaRG cells. In db/db mice, P17 promoted body weight and glycemia stabilization, decreased plasma triglycerides to the range of healthy mice and increased adiponectin (in high fat-fed mice) and insulin (in chow-fed mice) levels. It restored to the range of healthy mice the tissue levels and subcellular distribution of AdipoR1/R2, AMPKα-pT172 and PPARα-pS12. In liver, P17 reduced steatosis and apoptosis. The docking of P17 to AdipoR is reminiscent of the binding mechanism of adiponectin. To conclude, we have developed an AdipoR1/AdipoR2-targeted peptide that modulates adiponectin signalling pathways and has therapeutic relevance for T2D and obesity associated pathologies.

Identifiants :
  • DOI : 10.1080/1061186X.2019.1710840

Mots-clés :
  • (Anglais) phage display
  • (Anglais) type 2 diabetes
  • (Anglais) peptide
  • (Anglais) adiponectin
  • (Anglais) obesity
  • (Anglais) adiponectin receptors
  • (Anglais) metabolic syndrome