The use of animal models in diabetes research

Abstract

Diabetes is a disease characterized by a relative or absolute lack of insulin, leading to hyperglycaemia. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is due to an autoimmune destruction of the insulin-producing pancreatic beta cells, and type 2 diabetes is caused by insulin resistance coupled by a failure of the beta cell to compensate. Animal models for type 1 diabetes range from animals with spontaneously developing autoimmune diabetes to chemical ablation of the pancreatic beta cells. Type 2 diabetes is modelled in both obese and non-obese animal models with varying degrees of insulin resistance and beta cell failure. This review outlines some of the models currently used in diabetes research. In addition, the use of transgenic and knock-out mouse models is discussed. Ideally, more than one animal model should be used to represent the diversity seen in human diabetic patients.

Determining the Role of Sost and Sostdc1 During Fracture Healing

“…Both STZ and alloxan are similar in structure to glucose, thus these drugs are often administered in fasted animals to avoid competition with glucose [64]. Other tissues that express GLUT2, such as the liver and kidney, may also be vulnerable to STZ and alloxan effects, indicating a potential adverse or off target effects upon administering diabetic inducible drugs [68].…”

“…STZ is predominately used to induce T1DM, however this can also be used induce T2DM in rats by administrating a single high dose of STZ (100 mg/kg) intraperitoneally or intravenously to neonates. Neonates develop hyperglycemia 2 days post injection and maintain hyperglycemia after 6 weeks of age, revealing STZ as a multi-purpose drug model for diabetic studies [64].…”

“…The choice of drug induced or naturally developing diabetic model is often due to what is being studied. Naturally developing diabetes mouse models are used for studying autoimmune therapies and transplantation studies [64]. Inducible diabetes is ideal for observing drug or therapy effects and transplantation therapies, or where the primary focus is to lower hyperglycemia, such as a new insulin treatment in managing blood glucose levels [64].…”

“…Streptozotocin (STZ) (2-deoxy-2-(3-(methyl-3-nitrosoureido)-D-glucopyranose) is a nitrosourea compound that targets beta cells by entering via the glucose transporter, GLUT2, and is a widely used drug for inducing T1DM by inducing stress and DNA alkylation (cleaving) leading to cellular apoptosis [65,66]. STZ can either be administered intraperitoneally at a low dose (40-60 mg/g in 0.1M citrate buffer) continuously for 5 days or at a single high dosage (100-200 mg/kg), though the osteoporosis phenotype is dosage dependent [64]. High dose of STZ in rats is also toxic to T cells, inducing immunosuppression and making this an ideal model for transplantation studies [67].…”

Functional properties and sensory testing of whey protein concentrate sweetened with rebaudioside A

“…The animals that showed blood glucose levels equal or higher than 140 mg/dL in the fasting state and equal or higher than 250 mg/dL in the fed state were selected 27 . The levels of fasting blood glucose, blood glucose in the fed state and body weight, recorded for 3 days, were used to separate the two groups of diabetic animals so that each presented similar degrees of disease severity before starting treatment.…”