The use of mice in diabetes research: The impact of physiological characteristics, choice of model and husbandry practices

Abstract

Diabetes mellitus is characterised by hyperglycaemia, which results from an absolute or relative lack of insulin. Chronic and acute hyperglycaemia are associated with a range of health complications and an overall increased risk of mortality. Mouse models are vital in understanding the pathogenesis of this disease and its complications, as well as for developing new diabetes therapeutics. However, for experimental questions to be suitably tested, it is critical that factors inherent to the animal model are considered, as these can have profound impacts on experimental outcome, data reproducibility and robustness. In this review, we discuss key considerations relating to model choice, physiological characteristics (such as age, sex and genetic background) and husbandry practices and explore the impact of these on common experimental readouts used in preclinical diabetes research.

The use of mice in diabetes research: The impact of experimental protocols

“…24 Overall, these results highlight the role of welfare in scientific outcomes and the importance of consistency in practices and full disclosure of methods. 4.1.2 | Moving animals from holding rooms to procedure rooms In many animal units, mice are transported from holding rooms to procedure rooms prior to experimentation (e.g., GTTs). Conversely, because CGM requires mice to remain on their receiver mats for measurements to be taken, mice remain in their holding room for procedures.…”

“…3 However, many common preclinical end points in diabetes research can be impacted by the strain, sex and model of mouse chosen and so this should be carefully considered when planning in vivo experiments. 4 The choice of end points and protocols are also vital in experimental design to ensure that data are reproducible and translatable. 5 Indeed, it has been shown that poor study planning and implementation has direct implications on clinical translatability.…”

Acarbose Protects Glucolipotoxicity-Induced Diabetic Nephropathy by Inhibiting Ras Expression in High-Fat Diet-Fed db/db Mice

“…Mouse models are useful for identifying and testing novel therapeutic strategies that could translate into a better protection against human disease. The diabetogenic diet-fed C57BL/6 diabetic mice model has been widely used in DN research, and these mice are particularly susceptible to HFD-induced type 2 diabetes [ 17 ]. The HFD hyperinsulinemic db/db mice model displays a substantial glomerular pathology, including a mesangial matrix expansion and modest albuminuria [ 18 ].…”

The role of animal models in the treatment of diabetes mellitus

“…Streptozotocin is a Streptomyces chromogen-derived broad-spectrum antibacterial and anti-neoplastic nitrosourea derivative. It is a potent alkylating agent that has been shown to affect glucose transfer and glucokinase action and induce many DNA strand breaks [12]. Diabetes in mice may be caused by a single large dose of streptozotocin, most likely due to direct harmful effects.…”