Swine Models of Type 2 Diabetes Mellitus: Insulin Resistance, Glucose Tolerance, and Cardiovascular Complications

Abstract

In humans, diabetes mellitus (DM) is considered a heterogeneous metabolic disorder. Swine have been used as a model for many human conditions including type 1 (insulindeficient) and type 2 (insulin-resistant) DM research because of their phenotypic similarities to humans including: cardiovascular anatomy and function, metabolism, lipoprotein profile, size, tendency to obesity, and omnivorous habits. There is phenotypic overlap between the two types of DM and pig models show characteristics and complications of both. Streptozotocin and alloxan have been used to create insulin deficient diabetes in pigs. One of the most unique and useful phenotypes is that these insulin-deficient pigs develop more severe coronary atherosclerosis than nondiabetic controls. It is not fully understood why patients with either type 1 or type 2 DM have increased severity and diffuseness of atherosclerosis compared with nondiabetic patients. The current human epidemic of type 2 DM and its attendant cardiovascular complications underscore the unmet need for creating a useful, readily available animal model of type 2 insulin resistant DM that also develops coronary artery atherosclerosis. The phenotypic susceptibility to coronary atherosclerosis makes pigs an attractive species to identify causative mechanisms. Suggested criteria for validation of an animal model of humanoid type 2 DM are described. The goal would be to develop a useful animal model for mechanistic studies as well as to develop and test novel therapeutics both for type 2 DM as well as its cardiovascular complications.

Lean and obese pig breeds exhibit differences in prenatal gene expression profiles of muscle development

“…These results suggested that Mstn might play roles as not only a regulator but also a paracrine factor, which is consistent with a previous study (Guernec et al, 2003). Furthermore, swine, especially Yorkshire pigs, are typically used as a model for type-1 or type-2 diabetes mellitus in previous studies (Suzuki et al, 2001;Natarajan et al, 2002;Bellinger et al, 2006). Guo et al (2012) found that inhibition of Mstn might be an effective treatment for diabetes.…”

Proteomic profiling of animal models mimicking skeletal muscle disorders

“…More specialized metabolic investigations would study the mechanisms of aberrant insulin signalling during hormonal resistance using isotopic measurements of intracellular metabolic pathway fluxes in peripheral organs, such as liver and muscle. In addition, metabolic changes on the level of the regulation of glycolysis versus gluconeogenesis, citric acid cycle fluxes, sources of plasma glucose, nutrient oxidation and futile metabolic cycle fluxes also have to be taken into account if one wants to fully understand the phenotype of a new animal model of diabetes [50][51][52].…”

β-catenin protein utilized by Tumour necrosis factor-α in porcine preadipocytes to suppress differentiation

“…Although rat preadipocytes and http://bmbreports.org BMB reports adipocytes lines are commonly used in obesity studies, it has been suggested that porcine preadipocytes are a better model for the study of obesity and its related disorders because porcine preadipocytes possess higher lipogenic capacity and similar lipogenic patterns to human adipocytes (21)(22)(23). Fernandez reported that guinea pigs could be used as models to study hepatic cholesterol and lipoprotein metabolism (24).…”