ArticleTranslational research : the journal of laboratory and clinical medicine2014
Tacrolimus and sirolimus have distinct effects on insulin signaling in male and female rats.
Article in Translational research : the journal of laboratory and clinical medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- The Effect of Liver Transplantation on Anti-Glycaemic Agents in Patients With Pre-Existing Diabetes Mellitus: A Population-Based Cohort Study.Journal of diabetes · 2025Observational
- Rescuing vascular dysfunction in dorsal pancreatic arteries prevents tacrolimus-induced glucose metabolism disorder in mice.Molecular medicine (Cambridge, Mass.) · 2025Article
- Tacrolimus induces insulin receptor substrate 1 hyperphosphorylation and inhibits mTORc1/S6K1 cascade in HL7702 cells.World journal of diabetes · 2025Article
- Autoimmune hepatitis: Towards a personalized treatment.World journal of hepatology · 2024Review
- Review
- Human Menstrual Blood-Derived Stem Cells Protect against Tacrolimus-Induced Islet Dysfunction via Cystathionine β-Synthase Mediated IL-6/STAT3 Inactivation.Biomolecules · 2024Article
- New-Onset Diabetes Mellitus after Kidney Transplantation.Journal of clinical medicine · 2024Review
- Novel Drugs for the Management of Diabetes Kidney Transplant Patients: A Literature Review.Life (Basel, Switzerland) · 2023Review
- Diabetic Kidney Disease in Post-Transplant Diabetes Mellitus: Causes, Treatment and Outcomes.Biomedicines · 2023Review
- Diabetes and Cardiovascular Risk in Renal Transplant Patients.International journal of molecular sciences · 2021Review
- Post-Transplantation Diabetes Mellitus.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2020Review
- FXR activation alleviates tacrolimus-induced post-transplant diabetes mellitus by regulating renal gluconeogenesis and glucose uptake.Journal of translational medicine · 2019Article
- The effects of addition of coenzyme Q10 to metformin on sirolimus-induced diabetes mellitus.The Korean journal of internal medicine · 2019Article
- Post-transplant diabetes mellitus in patients with solid organ transplants.Nature reviews. Endocrinology · 2019Review
- Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2018Review
- Article
- Effects of metformin on hyperglycemia in an experimental model of tacrolimus- and sirolimus-induced diabetic rats.The Korean journal of internal medicine · 2017Article
- Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes.Endocrine reviews · 2016Review
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Although the contribution of the immunosuppressants tacrolimus (TAC) and sirolimus (SIR) to the development of posttransplant diabetes mellitus (PTDM) are being increasingly recognized, the mechanisms of immunosuppressant-induced hyperglycemia are unclear. SIR induces insulin resistance predominantly, but is associated with β-cell dysfunction in rodents. TAC affects islet function but is associated with worsening insulin sensitivity in a few, and improvement in some, clinical studies. We sought to clarify the contributions of TAC and SIR to insulin resistance and islet function. Four groups of male and female Sprague-Dawley rats received TAC, SIR, TAC and SIR, or control for 2 weeks. All rats were administered an oral glucose challenge at the end of treatment. Half the groups were sacrificed 10 minutes after administration of regular insulin whereas the other half did not receive insulin before sacrifice. Liver, pancreas, fat, and muscle were harvested subsequently. Quantification of Western blots revealed that SIR and TAC plus SIR suppressed the phospho-Akt (pAkt)-to-Akt ratios in liver, muscle, and fat compared with control, regardless of sex. TAC alone did not impair the pAkt-to-Akt ratios in any of the tissues in male and female rats. β-Cell mass was reduced significantly after TAC treatment in male rats. SIR did not affect β-cell mass, regardless of sex. Our study demonstrated very clearly that SIR impairs insulin signaling, without any effect on β-cell mass, and TAC does not impair insulin signaling but reduces β-cell mass. Our efforts are key to understanding the mechanisms of immunosuppressant-induced hyperglycemia and to tailoring treatments for PTDM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.