Objectif This proposal is focused on the identification and biological validation of the metabolic pathways and key regulatory genes that control insulin sensitivity in Type 2 diabetes mellitus (T2DM). We are focusing on skeletal muscle because it is quantitatively the most important tissue involved in maintaining glucose homeostasis under insulin-stimulated conditions and it is a major site of insulin resistance in T2DM. Our central hypothesis is that alterations in insulin signal transduction to glucose transport contribute to the profound impairment in whole body glucose homeostasis and T2DM pathogenesis. Identification of the defects in T2DM can lead to the development of new therapeutic strategies to prevent and cure this disease. The proposal is divided into two main objectives: We will apply: 1) target identification platforms including microarray, proteomics and bioinformatics to identify dysregulated genes in normal glucose tolerant versus T2DM subjects or genetically modified model systems and 2) functional genomics to assign a physiological role of the identified targets in Aim 1 using cellular and whole-body approaches. We will focus on the mitogen-activated protein kinase family, the energy-sensing enzyme AMP-activated protein kinase, and the lipid intermediate metabolizing enzyme diacylglycerol kinase delta. Our previous work indicates that these candidates play a role in the regulation of glucose metabolism, triglyceride storage, and energy homeostasis. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicinephysiologyhomeostasisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Mots‑clés Diabetes insulin resistance metabolism skeletal muscle Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Appel à propositions ERC-2008-AdG Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil KAROLINSKA INSTITUTET Contribution de l’UE € 2 500 000,00 Adresse Nobels Vag 5 17177 Stockholm Suède Voir sur la carte Région Östra Sverige Stockholm Stockholms län Type d’activité Higher or Secondary Education Establishments Chercheur principal Juleen Rae Zierath (Prof.) Contact administratif Eva Gipperth (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire KAROLINSKA INSTITUTET Suède Contribution de l’UE € 2 500 000,00 Adresse Nobels Vag 5 17177 Stockholm Voir sur la carte Région Östra Sverige Stockholm Stockholms län Type d’activité Higher or Secondary Education Establishments Chercheur principal Juleen Rae Zierath (Prof.) Contact administratif Eva Gipperth (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
