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Zawartość zarchiwizowana w dniu 2024-05-29

Molecular pathways underlying decreased beta cell mass in diabetes mellitus


The two main forms of diabetes are type 1 and type 2 diabetes (T1D & T2D). They affect 30 million individuals in Europe, decreasing their life quality and expectancy. A reduction in pancreatic beta cell mass, caused by increased apoptosis and defective regeneration, is a key component of both T1D and T2D. The molecular mechanisms underlying decreased beta cell mass remain to be clarified. Molecular signalling 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 the apoptosis program and prevent regeneration. The aim of this proposal is to utilize functional genomics to identify pathways responsible for the reduction of beta cell mass in diabetes, and use this knowledge to define targets for intervention to preserve beta cell mass.
This will be reached through the following steps:
(1) Identification of the regulatory molecular pathways that control physiological beta cell mass through regeneration, differentiation and apoptosis.
(2) Use of functional genomics to identify key patho-physiological events in the above pathways that are responsible for reduction of beta cell mass in diabetes, with focus on the mechanisms regulating cytokine- and glucolipotoxicity-induced beta cell apoptosis.
(3) Intervention in the defective signal transduction pathways identified above using genetically modified mice, long-acting viral vectors and small interfering RNAs.
This step should identify and validate targets to preserve beta cell mass in diabetes. To achieve this goal, a consortium of leading European experts in the fields of beta cell diabetes research, functional genomics and bioinformatics has been established. The results to be obtained will foster the development of cutting-edge functional genomics technology and contribute to the development of novel therapies to prevent diabetes.

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