Diabetes models

Streptozotocin-induced Type 1 Diabetes

Type 1 Diabetes (T1D) is a deficiency in insulin production caused by a loss of insulin-producing β-cells of the pancreatic islets. Non-genetic animal models of diabetes are superior to the genetically determined ones because of their translatability to the clinic. T1D can be modeled by treating experimental animals (rats or mice) with Streptozotocin (STZ) has preferential toxicity toward pancreatic β-cells, which causes a reduction in insulin production, decreased levels of circulating insulin, and elevated blood glucose levels. Eventually, animals develop various diabetes-associated pathologies, such as diabetic nephropathy, cardiomyopathy, diabetic ulcers, etc. STZ-induced experimental model of T1D can be used for efficacy studies of anti-diabetic drugs, including agents acting on insulin-independent pathways and prevention of the accompanying pathology development.

Streptozotocin/High Fat Diet-induced Type 2 Diabetes 

Unlike type 1 diabetes, type 2 diabetes (T2D) is associated with resistance to insulin action. In order to develop the animal pathology model, the high-fat diet (HFD) is often used. HFD leads to the development of obesity, metabolic syndrome, and a decrease in insulin sensitivity in mice, in contrast to the low-fat diet (LFD). The combination of HFD and a single Streptozotocin (STZ) injection results in metabolic changes to distinguish Type 2 Diabetes, including peripheral insulin resistance and pancreas β-cell impairment. HFD/STZ-induced model of experimental T2D can be used for efficacy testing of anti-diabetic and antiobesity drugs. The induction of disease can be carried out in rats or mice. The model is suitable for the efficacy study of the drugs stimulating the production/release of insulin from β-cells, as well as drugs reducing the production of glucose in the liver, improving tissues’ sensitivity to insulin, regulating the production of incretins, etc.

Glucose Tolerance Test (GTT)

The glucose tolerance test measures the clearance rate of high glucose from organisms. GTT can be used for rapid pharmacological screening of anti-diabetic drug candidates in rodents by assessing the hypoglycemic activity of test substances following acute or chronic administration.

Insulin Tolerance Test (ITT) 

The insulin tolerance test (ITT) is a straightforward method for evaluating the sensitivity of insulin receptors in tissues by measuring blood glucose levels in circulation before and after bolus insulin injection. This technique can be used for rapid pharmacological screening of insulin-like drug candidates or insulin sensitivity modulators by assessing their hypoglycemic activity following acute or chronic administration. In a typical ITT experiment, bolus intraperitoneal injections of human insulin (0.75 U/kg) in a group of five C57BL/6N mice are used to induce hypoglycemia.

Obesity-induced Type 2 Diabetes

Obesity is associated with the development of many diseases, and the most common one among them is Type 2 Diabetes (T2D). The obesity-induced experimental model of T2D is characterized by significant weight gain, increased fasting glucose, insulin resistance, and a number of metabolic disorders, such as abnormal lipid metabolism, cardiovascular complications, nephropathy, etc. The obesity-induced T2D model C57BL/6J mice demonstrates good reproducibility and reliability of the obtained results. The model is generally used for pharmacological screening of anti-diabetic and anti-obesity drugs, as well as for the study of drugs intended for the treatment of diabetes and obesity side effects: diabetic nephropathy, cardiomyopathy, etc.

Glucose levels during the Insulin tolerance test (0.75 U/kg) in C57BL/6J male mice after 8 weeks of HFD. Values are expressed as means ± SEM of 10 mice per group. *p < 0.05 compared to Vehicle Group
Glucose levels during oral glucose tolerance test (2 g/kg) in C57BL/6J male mice after 8 weeks of HFD. Values are expressed as means ± SEM of 10 mice per group. *p < 0.05 compared to Vehicle Group