Porcine models for studying complications and organ crosstalk in diabetes mellitus

Abstract

The worldwide prevalence of diabetes mellitus and obesity is rapidly increasing not only in adults but also in children and adolescents. Diabetes is associated with macrovascular complications increasing the risk for cardiovascular disease and stroke, as well as microvascular complications leading to diabetic nephropathy, retinopathy and neuropathy. Animal models are essential for studying disease mechanisms and for developing and testing diagnostic procedures and therapeutic strategies. Rodent models are most widely used but have limitations in translational research. Porcine models have the potential to bridge the gap between basic studies and clinical trials in human patients. This article provides an overview of concepts for the development of porcine models for diabetes and obesity research, with a focus on genetically engineered models. Diabetes-associated ocular, cardiovascular and renal alterations observed in diabetic pig models are summarized and their similarities with complications in diabetic patients are discussed. Systematic multi-organ biobanking of porcine models of diabetes and obesity and molecular profiling of representative tissue samples on different levels, e.g., on the transcriptome, proteome, or metabolome level, is proposed as a strategy for discovering tissue-specific pathomechanisms and their molecular key drivers using systems biology tools. This is exemplified by a recent study providing multi-omics insights into functional changes of the liver in a transgenic pig model for insulin-deficient diabetes mellitus. Collectively, these approaches will provide a better understanding of organ crosstalk in diabetes mellitus and eventually reveal new molecular targets for the prevention, early diagnosis and treatment of diabetes mellitus and its associated complications.

Green Synthesis of Gold Nanoparticles Capped with Procyanidins from Leucosidea sericea as Potential Antidiabetic and Antioxidant Agents

“…It occurs as a result of the inefficient processing of insulin [11]. As of 2017, the population of adults between the ages of 20 and 79 that suffered from diabetes was 425 million [12]. This is equivalent to 9.9% of the world's population [12].…”

“…As of 2017, the population of adults between the ages of 20 and 79 that suffered from diabetes was 425 million [12]. This is equivalent to 9.9% of the world's population [12]. By estimation, this disease would have drastically increased by 48% in 28 years if not properly managed [13].…”

A decade of experience with genetically tailored pig models for diabetes and metabolic research

“…Recently, refined classification systems have been introduced to cover sub-phenotypes of prediabetes and of adult onset diabetes and to facilitate more personalized diabetes treatments (reviewed in Renner et al, 2020).…”

“…Traditionally, diabetic pig models have been generated by partial or total pancreatectomy, or by chemical destruction of the pancreatic beta cells using streptozotocin or alloxan. The advantages and problems of these treatments have been extensively reviewed recently (Renner et al, 2020). Feeding pigs with high-fat/high-energy diet results in obesity and insulin resistance (Renner et al, 2018), but rarely in clinical diabetes without further interventions.…”

Innovative use of animal models to advance scientific research

“…Large animals such as pigs have become increasingly studied for their immune response, and Pabst reviews these investigational opportunities (Pabst 2020). Renner et al review how pig models can provide robust models for the study of metabolic syndrome and diabetes mellitus (Renner et al 2020), while Zuidema and Sutovsky review how some have harnessed the genetics of pigs to better understand mitochondrial inheritance (Zuidema and Sutovsky 2020). Similarly, Zigo et al review approaches to study porcine sperm and related fertility as a model for humans (Zigo et al 2020), while Ibtisham reviews the use of spermatogonia stem cells in animal models (Ibtisham et al 2020).…”