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"Discovery of the molecular pathways regulating pancreatic beta cell dysfunction and apoptosis in diabetes using functional genomics and bioinformatics" [''Discovery of the molecular pathways regulating pancreatic beta cell dysfunction and apoptosis in diabetes using functional genomics and bioinformatics'']

The two main forms of diabetes mellitus are type 1 and type 2 diabetes (T1D and T2D). They affect 30 million individuals in Europe, decreasing their life quality and expectancy. Of particular concern is that the prevalence of both forms of diabetes is increasing; it is expected to double in the next two decades. A reduction in functional pancreatic beta cell mass, caused by progressive loss of beta cell function and increased apoptosis, is a key component of both T1D and T2D. The molecular mechanisms underlying this decreased functional beta cell mass remain to be clarified. Molecular signaling in the beta cells is decisive for their survival or death in diabetes. We hypothesize that crosstalk between key gene networks and insufficient protective responses, due to inherent features of beta cells, trigger dysfunction and the apoptosis program. This crosstalk is modulated by the genetic background of the individuals at risk, but it is presently unknown how candidate genes for diabetes affect beta cell function and survival, and how they interact with environmental agents that may trigger disease, e.g. glucolipotoxicity in T2D and viral infections in T1D. Against this background, the aim of the present proposal is to utilize functional genomics and advanced molecular biology and bioinformatics tools to identify molecular signatures and pathways responsible for beta cell dysfunction and apoptosis in diabetes, and to use this knowledge to define novel targets for intervention to preserve beta cell mass. [The two main forms of diabetes mellitus are type 1 and type 2 diabetes (T1D and T2D). They affect 30 million individuals in Europe, decreasing their life quality and expectancy. Of particular concern is that the prevalence of both forms of diabetes is increasing; it is expected to double in the next two decades. A reduction in functional pancreatic beta cell mass, caused by progressive loss of beta cell function and increased apoptosis, is a key component of both T1D and T2D. The molecular mechanisms underlying this decreased functional beta cell mass remain to be clarified. Molecular signaling in the beta cells is decisive for their survival or death in diabetes. We hypothesize that crosstalk between key gene networks and insufficient protective responses, due to inherent features of beta cells, trigger dysfunction and the apoptosis program. This crosstalk is modulated by the genetic background of the individuals at risk, but it is presently unknown how candidate genes for diabetes affect beta cell function and survival, and how they interact with environmental agents that may trigger disease, e.g. glucolipotoxicity in T2D and viral infections in T1D. Against this background, the aim of the present proposal is to utilize functional genomics and advanced molecular biology and bioinformatics tools to identify molecular signatures and pathways responsible for beta cell dysfunction and apoptosis in diabetes, and to use this knowledge to define novel targets for intervention to preserve beta cell mass.]



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pancreatic beta cell dysfunction