title: Pancreatic Beta Cell Survival and Signaling Pathways: Effects of Type 1 Diabetes-Associated Genetic Variants.
abstract: Type 1 diabetes (T1D) is a complex autoimmune disease in which pancreatic beta cells are specifically destroyed by the immune system. The disease has an important genetic component and more than 50 loci across the genome have been associated with risk of developing T1D. The molecular mechanisms by which these putative T1D candidate genes modulate disease risk, however, remain poorly characterized and little is known about their effects in pancreatic beta cells. Functional studies in in vitro models of pancreatic beta cells, based on techniques to inhibit or overexpress T1D candidate genes, allow the functional characterization of several T1D candidate genes. This requires a multistage procedure comprising two major steps, namely accurate selection of genes of potential interest and then in vitro and/or in vivo mechanistic approaches to characterize their role in pancreatic beta cell dysfunction and death in T1D. This chapter details the methods and settings used by our groups to characterize the role of T1D candidate genes on pancreatic beta cell survival and signaling pathways, with particular focus on potentially relevant pathways in the pathogenesis of T1D, i.e., inflammation and innate immune responses, apoptosis, beta cell metabolism and function.
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium. izortze.santingomez@osakidetza.eus.|Endocrinology and Diabetes Research Group, BioCruces Health Research Institute, CIBERDEM, Spain. izortze.santingomez@osakidetza.eus.
authors.forename: Izortze
authors.initials: I
authors.lastname: Santin
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Reinaldo S
authors.initials: RS
authors.lastname: Dos Santos
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Decio L
authors.initials: DL
authors.lastname: Eizirik
mesh_terms: D002470:Cell Survival / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods*; D056726:Genetic Association Studies / Q000379:methods*; D005819:Genetic Markers; D014644:Genetic Variation; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D005819:Genetic Markers
keywords: Apoptosis; Cytokines; Diabetes candidate genes; Inflammation; Overexpression vector; Pancreatic beta cells; Pancreatic islets; Small interfering RNA (siRNA); Type 1 diabetes