Department of Human Anatomy and Physiology, University of Johannesburg, Doornfontein 2028, South Africa.
Int J Mol Sci. 2023 Dec 23;25(1):240. doi: 10.3390/ijms25010240.
The unrelenting increase in the incidence of type 2 diabetes (T2D) necessitates the urgent need for effective animal models to mimic its pathophysiology. Zebrafish possess human-like metabolic traits and share significant genetic similarities, making them valuable candidates for studying metabolic disorders, including T2D. This review emphasizes the critical role of animal models in diabetes research, especially focusing on zebrafish as an alternative model organism. Different approaches to a non-genetic model of T2D in zebrafish, such as the glucose solution, diet-induced, chemical-induced, and combined diet-induced and glucose solution methods, with an emphasis on model validation using indicators of T2D, were highlighted. However, a significant drawback lies in the validation of these models. Some of these models have not extensively demonstrated persistent hyperglycemia or response to insulin resistance and glucose tolerance tests, depicted the morphology of the pancreatic β-cell, or showed their response to antidiabetic drugs. These tools are crucial in T2D pathology. Future research on non-genetic models of T2D in zebrafish must extensively focus on validating the metabolic deficits existing in the model with the same metabolic defects in humans and improve on the existing models for a better understanding of the molecular mechanisms underlying T2D and exploring potential therapeutic interventions.
2 型糖尿病（T2D）发病率的持续增加，迫切需要有效的动物模型来模拟其病理生理学。斑马鱼具有类似人类的代谢特征，并且具有显著的遗传相似性，使其成为研究代谢紊乱（包括 T2D）的有价值的候选对象。本综述强调了动物模型在糖尿病研究中的关键作用，特别关注斑马鱼作为替代模式生物。本文重点介绍了不同的非遗传 T2D 斑马鱼模型方法，如葡萄糖溶液法、饮食诱导法、化学诱导法和联合饮食诱导和葡萄糖溶液法，并强调了使用 T2D 指标对模型进行验证。然而，这些模型存在一个显著的缺点，即验证不足。其中一些模型没有广泛证明持续的高血糖或对胰岛素抵抗和葡萄糖耐量试验的反应，也没有描绘胰腺β细胞的形态，或者没有显示它们对抗糖尿病药物的反应。这些工具对于 T2D 病理学至关重要。未来关于斑马鱼非遗传 T2D 模型的研究必须广泛关注用与人类相同的代谢缺陷来验证模型中的代谢缺陷，并改进现有的模型，以更好地理解 T2D 的分子机制并探索潜在的治疗干预措施。
