Aims

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 (Fig. 1). The specific aims are:

• Identification of the regulatory molecular pathways that control physiological beta cell mass through regeneration, differentiation and apoptosis.
• Use of functional genomics to identify key pathophysiological 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.
• 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.

Figure 1 – General strategy proposed by the project SAVEBETA to identify targets for intervention to preserve beta cell mass in diabetes.