Objetivo Type 2 diabetes (T2D) affects worldwide at present about 250 million patients and an estimated 380 million in 2025. This epidemic has been ascribed to a collision between genes and an affluent society. Genetics of T2D has during recent years identified > 30 variants increasing susceptibility to T2D. Yet, these variants explain only 15% of the heritability of T2D. One reason could be that whole genome association studies can only detect common variants whereas identification of rare variants with stronger effects would require sequencing. A large part of this application is devoted to sequencing of affected family members from unique large pedigrees traced back to common ancestors around 1600. The advantage of using families is that identified variants can be tested for segregation with the trait. Genetic variants can influence expression of a gene in an allele specific manner. This will be explored by combining exome sequencing with sequencing of RNA from human islets.Impaired effects of the incretin hormones GLP-1 and GIP on the pancreatic islets represent central defects in T2D. Variants in the TCF7L2 and GIPR genes contribute to these defects. I will here explore the molecular mechanisms by which TCF7L2, the strongest T2D gene, causes T2D. GIP has unprecedented effects not only on islet function but also on body composition, blood flow and vascular complications in T2D. This application explores these effects and will test whether manipulation of GIP can mimic the normalization of glucose tolerance seen after gastric bypass surgery.Taken together, these general and targeted approaches are expected not only to provide new insights into the causes of T2D but also contribute with vital information for development of new treatments for T2D. Ámbito científico medical and health sciencesclinical medicinesurgerymedical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesgeneticsgenomes Programa(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) Tema(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Convocatoria de propuestas ERC-2010-AdG_20100317 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida MAX IV Laboratory, Lund University Aportación de la UE € 2 499 479,60 Dirección Paradisgatan 5c 22100 LUND Suecia Ver en el mapa Región Södra Sverige Sydsverige Skåne län Tipo de actividad Higher or Secondary Education Establishments Investigador principal Leif Christer Groop (Prof.) Contacto administrativo Jacqueline Postma (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo MAX IV Laboratory, Lund University Suecia Aportación de la UE € 2 499 479,60 Dirección Paradisgatan 5c 22100 LUND Ver en el mapa Región Södra Sverige Sydsverige Skåne län Tipo de actividad Higher or Secondary Education Establishments Investigador principal Leif Christer Groop (Prof.) Contacto administrativo Jacqueline Postma (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos