Impaired mitochondrial calcium uptake caused by tacrolimus underlies beta-cell failure

摘要: One of the most common side effects immunosuppressive drug tacrolimus (FK506) is increased risk new-onset diabetes mellitus. However, molecular mechanisms underlying this association have not been fully clarified. We studied therapeutic dose on mitochondrial fitness in beta-cells. demonstrate that impairs glucose-stimulated insulin secretion (GSIS) beta-cells through a previously unidentified mechanism. Indeed, causes decrease Ca2+ uptake, accompanied by altered respiration and reduced ATP production, eventually leading to impaired GSIS. Our observations individuate new fundamental mechanism responsible for augmented incidence following treatment. alters fluxes mitochondria, thereby compromising metabolism-secretion coupling