Replicating human diabetes: insights from a novel animal model.

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.