Replicating human diabetes: insights from a novel animal model.

IF 3.1 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Silvia Teixidó-Trujillo, Esteban Porrini, Luis Manuel Menéndez-Quintanal, Armando Torres-Ramírez, Cecilia Fumero, Ana E Rodríguez-Rodríguez
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Abstract

Type 2 diabetes is considered the pandemic of the 21st century. The pathogenesis of diabetes is complex and multifactorial, and its understanding is crucial for its prevention and treatment. Nevertheless, the pathogenesis of beta cell dysfunction remains unclear. This gap in knowledge could be related to a lack of appropriate pre-clinical models of type 2 diabetes. Current animal models, mostly genotypic and monogenic, do not fully reflect the pathophysiology of type 2 diabetes or associated organ damage. Therefore, a new pre-clinical model is needed. In this study we present a non-genotypic animal model of diabetes that combines obesity and the treatment with the diabetogenic immunosuppressor Tacrolimus (TAC). Sprague Dawley male rats were fed with a high-fat diet to establish obesity and metabolic syndrome. Then, TAC was administered for 6-9 months to induce chronic hyperglycaemia. These animals showed a decrease in Langerhans islets area and number, and development of islet fibrosis. There were also changes in pancreatic insulin and glucagon content, imbalance in the alpha/beta cell ratio and decrease in the expression of essential transcription factors MafA, FOXO1A, PDX-1 and NeuroD1. Altogether, this could be a more appropriate animal model to study the pathophysiology of diabetes and, eventually, related organ damage.

复制人类糖尿病:来自一种新型动物模型的见解。
2型糖尿病被认为是21世纪的大流行病。糖尿病的发病机制是复杂的、多因素的,了解糖尿病的发病机制对预防和治疗至关重要。然而,β细胞功能障碍的发病机制尚不清楚。这种知识上的差距可能与缺乏适当的2型糖尿病临床前模型有关。目前的动物模型,大多是基因型和单基因的,不能完全反映2型糖尿病或相关器官损伤的病理生理。因此,需要一种新的临床前模型。在这项研究中,我们提出了一种非基因型糖尿病动物模型,该模型结合了肥胖和糖尿病免疫抑制剂他克莫司(TAC)的治疗。斯普拉格·道利雄性大鼠被喂食高脂肪食物,以建立肥胖和代谢综合征。然后给药6-9个月,诱导慢性高血糖。这些动物的朗格汉斯胰岛面积和数量减少,胰岛纤维化发展。胰腺胰岛素和胰高血糖素含量发生变化,α / β细胞比例失衡,必需转录因子MafA、FOXO1A、PDX-1和NeuroD1表达减少。总之,这可能是一个更合适的动物模型来研究糖尿病的病理生理,并最终研究相关的器官损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
9.80
自引率
0.00%
发文量
98
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Endocrinology and Metabolism publishes original, mechanistic studies on the physiology of endocrine and metabolic systems. Physiological, cellular, and molecular studies in whole animals or humans will be considered. Specific themes include, but are not limited to, mechanisms of hormone and growth factor action; hormonal and nutritional regulation of metabolism, inflammation, microbiome and energy balance; integrative organ cross talk; paracrine and autocrine control of endocrine cells; function and activation of hormone receptors; endocrine or metabolic control of channels, transporters, and membrane function; temporal analysis of hormone secretion and metabolism; and mathematical/kinetic modeling of metabolism. Novel molecular, immunological, or biophysical studies of hormone action are also welcome.
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