ArticleThe Journal of clinical investigation1996
Effects of tacrolimus (FK506) on human insulin gene expression, insulin mRNA levels, and insulin secretion in HIT-T15 cells.
Article in The Journal of clinical investigation, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.
- Risk factors for new-onset diabetes mellitus after kidney transplantation: A systematic review and meta-analysis.Journal of diabetes investigation · 2021Pooled it
- Integrative analyses of 16S rDNA sequencing and serum metabolomics demonstrate significant roles for the oral microbiota and serum metabolites in post-kidney transplant diabetes mellitus.Microbiology spectrum · 2025Article
- Early retinal neurovascular findings in post-transplant diabetes mellitus patients without clinical signs of diabetic retinopathy.International journal of retina and vitreous · 2023Article
- mTOR-inhibitors and post-transplant diabetes mellitus: a link still debated in kidney transplantation.Frontiers in medicine · 2023Review
- Progress of new-onset diabetes after liver and kidney transplantation.Frontiers in endocrinology · 2023Review
- Synthetic Pharmacotherapy for Systemic Lupus Erythematosus: Potential Mechanisms of Action, Efficacy, and Safety.Medicina (Kaunas, Lithuania) · 2022Review
- Dynamic changes in β-cell [CaMolecular metabolism · 2022Article
- Posttransplant Diabetes Mellitus and Immunosuppression Selection in Older and Obese Kidney Recipients.Kidney medicine · 2022Article
- Management of post-transplant diabetes: immunosuppression, early prevention, and novel antidiabetics.Transplant international : official journal of the European Society for Organ Transplantation · 2021Review
- Differential Effects of Voclosporin and Tacrolimus on Insulin Secretion From Human Islets.Endocrinology · 2020Article
- Late Conversion From Calcineurin Inhibitors to Belatacept in Kidney-Transplant Recipients Has a Significant Beneficial Impact on Glycemic Parameters.Transplantation direct · 2020Article
- Review
- Therapeutic potential of coenzyme QScientific reports · 2019Article
- Improved Glucose Tolerance in a Kidney Transplant Recipient With Type 2 Diabetes Mellitus After Switching From Tacrolimus To Belatacept: A Case Report and Review of Potential Mechanisms.Transplantation direct · 2018Article
- Temporal Changes on the Risks and Complications of Posttransplantion Diabetes Mellitus Following Cardiac Transplantation.Journal of transplantation · 2018Article
- Impaired mitochondrial calcium uptake caused by tacrolimus underlies beta-cell failure.Cell communication and signaling : CCS · 2017Article
- Prevalence, predictors, and outcomes of steroid-induced hyperglycemia in hospitalized patients with hematologic malignancies.Endocrine · 2017Article
- Prediabetes in Pediatric Recipients of Liver Transplant: Mechanism and Risk Factors.The Journal of pediatrics · 2017Article
- Beneficial effects of mycophenolate mofetil on cardiotoxicity induced by tacrolimus in wistar rats.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Differential influence of tacrolimus and sirolimus on mitochondrial-dependent signaling for apoptosis in pancreatic cells.Molecular and cellular biochemistry · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
FK506 (tacrolimus) is an immunosuppressive drug which interrupts Ca2+-calmodulin-calcineurin signaling pathways in T lymphocytes, thereby blocking antigen activation of T cell early activation genes. Regulation of insulin gene expression in the beta cell may also involve Ca2+-signaling pathways and FK506 has been associated with insulin-requiring diabetes mellitus during clinical use. The purpose of this study was to characterize the effects of FK506 on human insulin gene transcription, insulin mRNA levels, and insulin secretion using as a model the HIT-T15 beta cell line. FK506 had no acute effect on insulin secretion in the HIT cell, but caused a reversible time- and dose-dependent (10(-9)-10(-6) M) decrease in HIT cell insulin secretion. Decreased insulin secretion in the presence of FK506 was also accompanied by a dose-dependent decrease in HIT cell insulin content, insulin mRNA levels, and expression of a human insulin promoter-chloramphenicol acetyl transferase (CAT) reporter gene. FK506 decreased HIT cell expression of the human insulin promoter-CAT reporter gene by 40% in the presence of both low (0.4 mM) at high (20 mM) glucose concentrations. Western blot analysis of HIT cell proteins gave evidence for the presence of calcineurin in the HIT cell. These findings suggest that FK506 may have direct effects to reversibly inhibit insulin gene transcription, leading to a decline in insulin mRNA levels, insulin synthesis, and ultimately insulin secretion.
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