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2016-05-04 - Colloque/Présentation - communication orale - Anglais - 1 page(s)

Crombez Déborah, Muller Robert , Burtea Carmen , "Potential therapeutic peptides targeted to adiponectin receptors, able to modulate the AMPK pathway and regulate the glucose and lipid metabolism" in Diabetes Kongress , Berlin, Allemagne, 2016

  • Codes CREF : Histologie (DI3212), Sciences biomédicales (DI3200), Endocrinologie (DI3322), Biochimie pharmaceutique (DI3491), Biologie moléculaire (DI3111), Diabétologie (DI3373), Biologie cellulaire (DI311D)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108)
  • 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)

Abstract(s) :

(Anglais) Often associated with metabolic syndrome, type 2 diabetes is increasingly linked to obesity. By binding to its receptors (AdipoR1 and AdipoR2), adiponectin activates a key enzyme in cellular homeostasis, the 5’ adenosine monophosphate-activated protein kinase (AMPK). Adiponectin and AMPK pathway play an important role in the regulation of glycaemia and of lipid metabolism, representing thus a promising tool for the treatment of diabetic and obese patients. Our goal was to develop a therapeutic agent able to specifically bind the adiponectin receptors and modulate the transduction pathways involved in glucose and metabolism regulation. Three peptides (P16, P17 and P18) targeted to a fragment of the C-terminal extracellular domain of AdipoR were identified by phage display; this fragment is identical in both receptors in humans and mice. As demonstrated by immunohistochemistry and immunofluorescence, P17 shows a preference for AdipoR2 expressed by the liver, whereas P18 seems to be specific to AdipoR1 expressed by the muscle and beta cells in the pancreas. The pharmacologic activity of peptides has been evaluated on hepatic cells by measuring the level of AMPK phosphorylation (AMPKp). P17 and P18 were able to induce AMPKp and glycolysis in hepatic cells incubated in a medium supplemented with glucose and/or fatty acids; P18 is also able to activate the Krebs cycle. The pharmacologic activities of peptides are currently evaluated on skeletal muscle cells in the same conditions. After in vitro validation, the therapeutic activity of the selected peptides will be evaluated in vivo on a mouse model becoming spontaneously obese and diabetic.


Mots-clés :
  • (Anglais) phage display
  • (Anglais) AMPK
  • (Anglais) therapy
  • (Anglais) diabetes
  • (Anglais) peptides