Background: One of the most common side effects of the immunosuppressive drug tacrolimus (FK506) is the increased risk of new-onset diabetes mellitus. However, the molecular mechanisms underlying this association have not been fully clarified. Methods: We studied the effects of the therapeutic dose of tacrolimus on mitochondrial fitness in beta-cells. Results: We demonstrate that tacrolimus impairs glucose-stimulated insulin secretion (GSIS) in beta-cells through a previously unidentified mechanism. Indeed, tacrolimus causes a decrease in mitochondrial Ca2+ uptake, accompanied by altered mitochondrial respiration and reduced ATP production, eventually leading to impaired GSIS. Conclusion: Our observations individuate a new fundamental mechanism responsible for the augmented incidence of diabetes following tacrolimus treatment. Indeed, this drug alters Ca2+ fluxes in mitochondria, thereby compromising metabolism-secretion coupling in beta-cells.
CITATION STYLE
Lombardi, A., Trimarco, B., Iaccarino, G., & Santulli, G. (2017). Impaired mitochondrial calcium uptake caused by tacrolimus underlies beta-cell failure. Cell Communication and Signaling, 15(1). https://doi.org/10.1186/s12964-017-0203-0
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