- To build and manage a European research network focusing on NIDDM susceptibility genes.
- To establish a European database and cell-line bank from families with well-documented NIDDM.
- To train young European researchers in the field of Molecular Biology of NIDDM.
Understanding the genetic etiology of non insulin-dependent diabetes mellitus critical for envisioning effective strategies to prevent and to treat, ultimately to cure this common disease. The main objective of the present proposal is the building and managing of a European research network which will focus on the identification of the genetic alterations in the mechanism of insulin action resulting in the susceptibility to NIDDM. The network has four measurable aims:
1. Facilitate the identification of NIDDM genes by establishing a European database and cell-line bank containing information (family history, medical history, clinical, and laboratory data) and specimens, (lymphoblastoid cell lines, skin fibroblasts and sera) on families with well-documented NIDDM. This material will be available to all qualified European researchers in the field of insulin action and NIDDM etiology upon accomplishment of this task.
2. Disseminate know-how information and specialized technologies which are presently available only in a few European laboratories working in the field of insulin action.
3. Training young European researchers in the field of molecular biology of NIDDM by favouring the mobility between the participating laboratories.
4. Coordinate the research activities in the participating laboratories as a prerequisite to the possible launching of share cost projects at a later stage.
This work will involve the systematic scanning for alterations in potential candidate genes coding for elements in the signalling cascade used by insulin (these include SHC, MAP kinase, PI-3-kinase, Glut1, rab4, Glycogen Synthase kinase, Protein Phosphatase 1, ane IGF-I Binding Proteins). In order to detect both quantitative alterations in the expression of these genes and mutations, solution hybridization/RNase protection, denaturing gradient gel electrophoresis and single stranded conformational polymorphism will be adopted as screening procedures. Bioptical specimens of muscle and fat tissue will be used as starting material.