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Updated: Jun 5, 2026
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High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
Published on: January 23, 2018
Unique cellular and mitochondrial defects mediate FK506-induced islet β-cell dysfunction.
Nassir Rostambeigi1, Ian R Lanza, Petras P Dzeja
1Division of Endocrinology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Transplantation
|January 5, 2011
Summary
Tacrolimus (FK506) impairs pancreatic beta-cell function by reducing insulin secretion and mitochondrial density. These effects on mitochondrial function may explain FK506-induced posttransplantation diabetes mellitus.
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- Posttransplantation diabetes mellitus (PTDM) is a common complication after organ transplantation.
- Tacrolimus (FK506) is a widely used immunosuppressant associated with PTDM development.
Purpose of the Study:
- To elucidate the biological mechanisms underlying tacrolimus-induced PTDM.
- To investigate the impact of FK506 on pancreatic beta-cell function and viability.
Main Methods:
- INS-1 cells and isolated rat islets were treated with FK506.
- Assessed cell viability, apoptosis, proliferation, insulin secretion, and mitochondrial function (respiration, content, bioenergetics).
- Utilized microarray analysis and quantitative PCR for gene expression profiling.
Main Results:
- FK506 significantly decreased cell replication, viability, insulin secretion, and mitochondrial content and function.
- Comparable effects were observed between FK506 and cyclosporine A.
- FK506 altered pathways involved in ATP metabolism and cytoskeleton remodeling, down-regulating PGC1-α mRNA.
Conclusions:
- FK506 reduces insulin secretion and mitochondrial density/function in pancreatic beta-cells at pharmacologically relevant concentrations.
- These mitochondrial effects, without altering apoptosis, suggest a primary role in FK506-induced PTDM.
- Nuclear factor of activated T-cells identified as a potential mediator of FK506's gene expression effects.
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