Aproximacions a l'Estudi de les Causes de la Diabetis Mellitus i Desenvolupament de Noves Teràpies

Study objective: To determine the role of hyperinsulinemina and insulin resistance in the onset of non-insulin-dependent-diabetes-mellitus (NIDDM). To study the mechanisms responsible for the developement of microvascular complications of diabetes. To establish a new therapeutical approach for insulin-dependent diabetes mellitus (IDDM) involving endocrine pancreas regeneration by IGF-I. Design: Use of different transgenic animals models obtained in our laboratory ro study the causes of NIDDM, the secondary complications and evaluate new therapies. Setting: Transgenic mice expressing the following chimeric genes: RIP-I/IGF-I, RIIP-I/IGF-II, PEPCK/insulin, MLC/insulin, opsin/insulin, albumin/pp63, MLC/PC-I. Double transgenic mice expressing the following chimeric genes: MLC/glucokasine and RIP-I/IGF-II; MLC/glucokasine and PEPCK; PEPCK/c-\i myc\i0 and RIP-I/IGF-II. Non-obese diabetic mice (NOD). Patients: Control, NOD and transgenic mice: studies in pancreas and in isolated islets, eyes, kidney and liver. Interventions: Microinjection of chimeric genes into fertilized oocytes. Obtention and analysis of samples from different tissues. Glucose tolerance test. Histopathological and immunohistochemical studies. Measurements: The expression of different chimeric histopathological and immunohistochemical studies. Measurements: The expression of different chimeric genes and their effect on carbohydrate metabolism in the different tissues will be studied. Serum parameters will also be analyzed. Morphometric analysis of pancreas. Studies of the neovascularization of retina. IGF-I effect on endocrine pancreas regeneration in IDDM.