Objetivo The aim of this project is to combine biophysical, biochemical and morphological approaches to investigate the mechanisms which couple stimuli to insulin release in both normal pancreatic islets and in islets from animals with biabetes-like syndromes. Glucose-induced insulin release is modulated by several hormones and neurotransmitters. It has been hypothesized that these agents regulate insulin secretion, at least in part, by interacting with plasma membrane K- or Ca-channels. 1) This possibility will be investigated by simultaneous measurement intracellular Ca 2+ concentration (!Ca2+!i) and either membrane potential or ion channel activity. 2) The role of second messenger systems (G-proteins, protein kinase C and adenylate cyclase) will be evaluated using biophysical and biochemical methods. The perforated patch-clamp configuration will be used to study whole-cell current modulation. The role of G-proteins in all these processes will be investigated using activators (GTP analogues, AlF-4) and inhibitors (pertussis toxin) of G-proteins, purified G-protein subunits and specific antibodies against these subunits. 3) Despite the functional heterogeneity the islet behaves as a "syncithium". Intercellular coupling through gap junctions may also bring about signal synchronization so that less responsive cells may be induced to secrete by active neighbouring cells. In this regard: a) the relationship between the electrical properties of the B-cell and the functional heterogeneity of B-cells in terms of insulin secretion and biosynthesis will also be determined, and b) it will be also studied the regulation of the gap junctions (which are likely to form the structural basis for the islet to perform a synchronized response to nutrients and secretagogues). Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteins Programa(s) FP2-SCIENCE - Programme plan (EEC) to stimulate the international cooperation and interchange needed by European research scientists (SCIENCE), 1988-1992 Tema(s) Data not available Convocatoria de propuestas Data not available Régimen de financiación CSC - Cost-sharing contracts Coordinador Universidad de Alicante Aportación de la UE Sin datos Dirección S/N,Crta. de Valencia 03071 San Juan de Alicante España Ver en el mapa Coste total Sin datos Participantes (3) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo Centre Médical Universitaire Suiza Aportación de la UE Sin datos Dirección 1,Rue Michel Servet 1211 Genève Ver en el mapa Coste total Sin datos THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Reino Unido Aportación de la UE Sin datos Dirección Parks Road OX1 3PT Oxford Ver en el mapa Coste total Sin datos Universidade de Coimbra Portugal Aportación de la UE Sin datos Dirección 3049 Coimbra Ver en el mapa Coste total Sin datos