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Updated: Jun 1, 2025
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Tacrolimus and diabetic rodent models
Minyan Qian1,2, Mengmeng Guan1,2, Liying Wang1
1Department of Pharmacy, The First People's Hospital of Changzhou/The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.
Abstract:
Tacrolimus (TAC) is an immunosuppressant widely utilized in organ transplantation. One of its primary adverse effects is glucose metabolism disorder, which significantly increases the risk of diabetes. Investigating the molecular mechanisms underlying TAC-induced diabetes is essential for developing effective prevention and treatment strategies for these adverse effects. In addition, TAC can induce cost-effective, non-obese animal models of diabetes, where the metabolic parameter changes closely resemble those observed during the onset and progression of type 2 diabetes (T2DM), post-transplantation diabetes mellitus (PTDM), and associated complications. This review, based on articles indexed in PubMed up to August 19, 2024, identified 48 studies focusing on TAC-induced diabetic rodent models and 22 studies exploring the effects of TAC on diabetic or obese rodent models. These studies were systematically summarized based on TAC dosage, route of administration, duration of administration, and glucose metabolism indices used for evaluation. Additionally, the impact of TAC dose reduction or discontinuation on glucose metabolism was assessed, along with pharmacological agents that modulate TAC-induced diabetes, including anti-diabetic medications, anti-inflammatory and antioxidant compounds, biologics, and antibiotics. Key signaling pathways implicated in TAC-induced diabetes include CaN/NFAT, PI3K/AKT/mTOR, and TGF-β/Smad, all of which impair islet β-cell function, thereby contributing to diabetes development. This review provides a concise summary of the characteristics of relevant murine models, offering valuable guidance for selecting appropriate and economical animal models for future research.
Insights
Tacrolimus (TAC), an immunosuppressant, can cause diabetes by impairing islet beta-cell function. This review summarizes TAC-induced diabetes models and potential therapeutic strategies to mitigate this adverse effect.
Area of Science:
- Immunology
- Endocrinology
- Pharmacology
Background:
- Tacrolimus (TAC) is a vital immunosuppressant in organ transplantation.
- A significant adverse effect of TAC is glucose metabolism disorder, increasing diabetes risk.
- Understanding TAC-induced diabetes mechanisms is crucial for prevention and treatment.
Purpose of the Study:
- To systematically review rodent models of Tacrolimus-induced diabetes.
- To summarize key molecular pathways involved in TAC-induced diabetes.
- To assess interventions for managing TAC-induced glucose metabolism disorders.
Main Methods:
- Systematic literature review of PubMed-indexed articles up to August 19, 2024.
- Analysis of 48 studies on TAC-induced diabetic rodent models and 22 on TAC effects in diabetic/obese models.
- Summarization based on TAC dosage, administration, duration, and glucose metabolism indices.
Main Results:
- TAC impairs islet beta-cell function via CaN/NFAT, PI3K/AKT/mTOR, and TGF-β/Smad pathways.
- TAC induces non-obese diabetic models mimicking type 2 diabetes and post-transplantation diabetes mellitus.
- Dose reduction, discontinuation, and various pharmacological agents can modulate TAC-induced diabetes.
Conclusions:
- TAC-induced diabetes is a significant concern in transplantation.
- Rodent models provide valuable insights into diabetes pathogenesis and treatment.
- This review guides the selection of appropriate animal models for future research.
