We are striving towards the identification of disease-modifying mechanisms that protect endogenous insulin release and diabetes development. Ion channels play overarching roles as sensors of cellular activity and control long-term adaptation of the endocrine pancreatic islet to the environmental demands. Our goals concern signals involved in cellular responses to beta-cell overload: 1)Role of voltage-gated Ca2+ channel subunits and Ca2+ signals for beta-cell gene expression, differentiation status, secretory capacity and diabetes 2)Role of non-voltage-gated ion channels and ligands and mechanical signals for beta-cell gene expression, differentiation status, secretory capacity and diabetes. Novel therapeutic approaches: Superparamagnetic nanoparticles as tools for targeted receptor activation and triggering of mechanosensing