Silvia Teixidó-Trujillo, Esteban Porrini, Luis Manuel Menéndez-Quintanal, Armando Torres-Ramírez, Cecilia Fumero, Ana E Rodríguez-Rodríguez
{"title":"Replicating human diabetes: insights from a novel animal model.","authors":"Silvia Teixidó-Trujillo, Esteban Porrini, Luis Manuel Menéndez-Quintanal, Armando Torres-Ramírez, Cecilia Fumero, Ana E Rodríguez-Rodríguez","doi":"10.1152/ajpendo.00226.2025","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Endocrinology and metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1152/ajpendo.00226.2025","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
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.
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.