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Updated: Feb 18, 2026
Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Impaired mitochondrial calcium uptake caused by tacrolimus underlies beta-cell failure
Angela Lombardi1, Bruno Trimarco2, Guido Iaccarino3
1Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA.
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.
Insights
Tacrolimus impairs insulin secretion by affecting beta-cell mitochondria. This drug disrupts calcium uptake and ATP production, leading to new-onset diabetes mellitus.
Area of Science:
- Biochemistry
- Cell Biology
- Endocrinology
Background:
- Tacrolimus (FK506) is an immunosuppressant linked to increased risk of new-onset diabetes mellitus.
- The precise molecular mechanisms driving this side effect remain unclear.
Purpose of the Study:
- To investigate the impact of therapeutic tacrolimus doses on mitochondrial function in pancreatic beta-cells.
Main Methods:
- Studied the effects of tacrolimus on beta-cell mitochondrial fitness.
- Assessed mitochondrial calcium (Ca2+) uptake, respiration, and ATP production.
Main Results:
- Tacrolimus significantly impairs glucose-stimulated insulin secretion (GSIS) in beta-cells.
- Observed reduced mitochondrial Ca2+ uptake, altered respiration, and decreased ATP production.
- These mitochondrial dysfunctions are linked to impaired GSIS.
Conclusions:
- Identified a novel mechanism where tacrolimus disrupts beta-cell function.
- Tacrolimus alters mitochondrial calcium fluxes, compromising the coupling of metabolism and insulin secretion.
- This provides a fundamental explanation for tacrolimus-induced diabetes.
