Objectif "Dipeptidyl peptidase-4 (DPP-4) is an exoprotease that cleaves N-terminal dipeptides from several substrates such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GLP), impairing the function of the incretin system, which is of key importance for glucose homeostasis. Indeed, DPP4 inhibitors are currently in clinical use for type 2 diabetes. The host group has described for the first time that DPP4 is secreted by adipose and strongly correlates with adipocyte volume and parameters of the metabolic syndrome and is decreased to the lean level after weight reduction in humans. Moreover, novel data obtained in the host group suggest that DPP4 may impair insulin sensitivity in an auto- and paracrine manner. Thus, DPP4 arises as a novel adipokine potentially linking obesity to the metabolic syndrome. Since there is a growing interest in anti-diabetic therapies based on DPP4 inhibition, a deeper understanding of the role of adipose DPP4 on the onset and progression of insulin resistance is needed. This project aims to explore the impact of adipose DPP4 deletion in diet- induced obesity (ADDIO). For this purpose the host group is generating an adipose-specific DPP4 knockout mouse to prove a causal roleof this protein in the development of the metabolic syndrome. Our global aim will be pursued following a 3 step strategy: Firstly, we will assess the impact of adipose DPP4 genetic deletion by characterizing the metabolic phenotype of adipose-specific DPP4 knockout mice.We will next determine the impact of genetic deletion of adipose DPP4 on the development of diet-induced impaired glucose tolerance and insulin resistance. Finally, we will explore the mechanism responsible for the potential protective/delaying effect of adipose DPP4 genetic deletion on impaired glucose tolerance and insulin resistance in obesity." Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesbasic medicinephysiologyhomeostasismedical and health scienceshealth sciencesnutritionobesity Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2012-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Appel à propositions FP7-PEOPLE-2012-IEF Voir d’autres projets de cet appel Régime de financement MC-IEF - Intra-European Fellowships (IEF) Coordinateur DEUTSCHE DIABETES FORSCHUNGSGESELLSCHAFT EV Contribution de l’UE € 168 794,40 Adresse AUF M HENNEKAMP 65 40225 Duesseldorf Allemagne Voir sur la carte Région Nordrhein-Westfalen Düsseldorf Düsseldorf, Kreisfreie Stadt Type d’activité Research Organisations Contact administratif Jürgen Eckel (Prof.) Liens Contacter l’organisation Opens in new window Coût total Aucune donnée
