Objectif Currently, there is an urgent need to understand the pathogenesis underpinning insulin resistance (IR) and type 2 diabetes (T2DM), due to their dramatically increasing prevalence. Glucocorticoids (GCs) are potent modulators of skeletal (Sk) muscle insulin sensitivity, as exemplified in patients with GC excess, Cushing’s syndrome, who develop IR and T2DM. Importantly, increased GC generation locally in muscle may contribute to the phenotype in T2DM patients. Although the precise molecular mechanisms driving IR in both T2DM and Cushing’s syndrome are unclear, dysregulated lipid metabolism is a common feature of insulin resistant muscle. This proposal aims to identify how GCs regulate intramyocellular lipid metabolism, and how this impacts on muscle insulin sensitivity. In addition, we will test a novel therapeutic target involved in mediating the metabolic actions of GCs, recently described by Dr Carolyn Cummins, the supervisor of the outgoing phase of this proposal. The complementary expertise in integrative molecular physiology of Dr Cummins, and of the Experienced Researcher, Dr Stuart Morgan, dovetail nicely within an established multi-disciplinary collaborative network of pharmacologists, molecular biologists and analytical chemists at the University of Toronto that have a unifying goal to uncover novel mechanisms regulating IR. Specifically, this proposal employs a systems approach by integrating both in vivo and in vitro pharmacological and genetic manipulation, with lipidomic/proteomic profiling and in-depth molecular characterisations. This novel strategy will significantly advance our understanding of key processes regulating insulin sensitivity in Sk muscle, a process essential for normal glucose homeostasis. Champ scientifique medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2014-GF - Marie Skłodowska-Curie Individual Fellowships (IF-GF) Appel à propositions H2020-MSCA-IF-2014 Voir d’autres projets de cet appel Régime de financement MSCA-IF-GF - Global Fellowships Coordinateur THE UNIVERSITY OF BIRMINGHAM Contribution nette de l'UE € 255 349,80 Adresse Edgbaston B15 2TT Birmingham Royaume-Uni Voir sur la carte Région West Midlands (England) West Midlands Birmingham Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 255 349,80 Partenaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire Partenaire Les organisations partenaires contribuent à la mise en œuvre de l’action, mais ne signent pas la convention de subvention. THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO Canada Contribution nette de l'UE € 0,00 Adresse KINGS COLLEGE CIRCLE 27 M5S 1A1 Toronto Voir sur la carte Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 157 622,40
