Qian Minyan, Guan Mengmeng, Wang Liying, Hu Nan
Department of Pharmacy, The First People's Hospital of Changzhou/The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.
College of Pharmaceutical Sciences, Soochow University, Suzhou, 215127, Jiangsu, China.
Pharmacol Rep. 2025 Apr;77(2):333-354. doi: 10.1007/s43440-024-00693-3. Epub 2025 Jan 21.
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.
他克莫司（TAC）是一种广泛应用于器官移植的免疫抑制剂。其主要不良反应之一是葡萄糖代谢紊乱，这显著增加了患糖尿病的风险。研究TAC诱导糖尿病的分子机制对于制定针对这些不良反应的有效预防和治疗策略至关重要。此外，TAC可以诱导出具有成本效益的非肥胖糖尿病动物模型，其中代谢参数的变化与2型糖尿病（T2DM）、移植后糖尿病（PTDM）及其相关并发症发病和进展过程中观察到的变化非常相似。本综述基于截至2024年8月19日在PubMed上索引的文章，确定了48项关注TAC诱导糖尿病啮齿动物模型的研究和22项探索TAC对糖尿病或肥胖啮齿动物模型影响的研究。这些研究根据TAC剂量、给药途径、给药持续时间以及用于评估的葡萄糖代谢指标进行了系统总结。此外，还评估了TAC剂量减少或停药对葡萄糖代谢的影响，以及调节TAC诱导糖尿病的药物制剂，包括抗糖尿病药物、抗炎和抗氧化化合物、生物制剂和抗生素。TAC诱导糖尿病涉及的关键信号通路包括CaN/NFAT、PI3K/AKT/mTOR和TGF-β/Smad，所有这些都会损害胰岛β细胞功能，从而导致糖尿病的发展。本综述简要总结了相关小鼠模型的特征，为未来研究选择合适且经济的动物模型提供了有价值的指导。
