Cyclosporine and Its Effects on Diabetes After Transplantation
Author Information
Author(s): Borlak Jürgen, Niehof Monika
Primary Institution: Fraunhofer Institute of Toxicology and Experimental Medicine, Medical School of Hannover, Hannover, Germany
Hypothesis
The study investigates the molecular mechanisms by which cyclosporine induces posttransplantation diabetes mellitus (PTDM) through the dysfunction of hepatic nuclear factors HNF4alpha and HNF1alpha.
Conclusion
Cyclopsorine treatment represses the expression and activity of HNF4alpha and HNF1alpha, leading to impaired glucose metabolism and increased risk of diabetes in transplant patients.
Supporting Evidence
- Cyclopsorine treatment significantly reduced HNF4alpha protein and gene expression in cell lines.
- In Zucker diabetic fatty rats, HNF4alpha and insulin gene expressions were significantly repressed.
- The study identified a novel NFAT binding site in the HNF4alpha promoter that is affected by cyclosporine.
Takeaway
This study shows that cyclosporine, a drug used after organ transplants, can make it harder for the body to manage sugar, which might lead to diabetes.
Methodology
The study involved experiments on rat insulinoma cell lines, human epithelial cell lines, and Zucker diabetic fatty rats to assess the effects of cyclosporine on gene expression and protein activity.
Limitations
The study primarily uses animal models and cell lines, which may not fully replicate human responses to cyclosporine.
Participant Demographics
The study included 14 patients with varying conditions, including colorectal liver metastasis and hepatocellular carcinoma.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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