Feasibility of large experimental animal models in testing novel therapeutic strategies for diabetes

Abstract

Diabetes is among the top 10 causes of death in adults and caused approximately four million deaths worldwide in 2017. The incidence and prevalence of diabetes is predicted to increase. To alleviate this potentially severe situation, safer and more effective therapeutics are urgently required. Mice have long been the mainstay as preclinical models for basic research on diabetes, although they are not ideally suited for translating basic knowledge into clinical applications. To validate and optimize novel therapeutics for safe application in humans, an appropriate large animal model is needed. Large animals, especially pigs, are well suited for biomedical research and share many similarities with humans, including body size, anatomical features, physiology, and pathophysiology. Moreover, pigs already play an important role in translational studies, including clinical trials for xenotransplantation. Progress in genetic engineering over the past few decades has facilitated the development of transgenic animals, including porcine models of diabetes. This article discusses features that attest to the attractiveness of genetically modified porcine models of diabetes for testing novel treatment strategies using recent technical advances.

Keywords: Pancreatic islet, Diabetes mellitus, Pig, Transgenic, Genetic engineering, Transplantation, Xenotransplantation

Core Tip: Safer and more effective therapeutics are urgently required for managing the diabetes epidemic. Mice have been used predominantly as preclinical models for basic research on diabetes, although murine models are not ideally suited for translating basic knowledge into clinical applications. This article discusses features that attest to the attractiveness of genetically modified porcine models of diabetes for testing novel treatment strategies using recent technical advances.