Metabolic Disease Models

Type I and II Diabetes Mellitus (DM)

DM is a group of metabolic diseases characterized by high blood glucose levels over a prolonged period, whose incidence is increasing worldwide at an alarming rate. DM exists in two fundamental types: Type-I (Insulin-Dependent Diabetes Mellitus – IDDM) and Type-II (Non Insulin-Dependent DM – NIDDM), the latter accounting for 90-95% of all diabetes. MIR offers a wide range of genetic and induced models of DM to help the discovery of novel therapeutic strategies for DM and DM and DM-related complications

Type-I Diabetes

a. Non-Obese Diabetic (NOD) mice

NOD mice represent the principal spontaneous experimental model for IDDM: in NOD mice, especially females, pathologic events start developing from the third week of age with the presentation of pancreatic islet antigens into the pancreatic lymphnodes, leading to insulitis within 15 weeks. These events trigger a strong autoimmune response against the pancreatic islets which leads to frank diabetes (fasting blood glucose ≥ 250 mg/dL) within 18 and 20 weeks of age.

b. Streptozotocin (STZ)-Induced Models

Single or multiple injections of STZ in mice or rats represent a widely used induced experimental model for IDDM: in this model, DM is induced in rats or mice through single or multiple intraperitoneal injections of STZ dissolved in citrate buffer. STZ is a cytotoxic agent which is highly selective for pancreatic β-cells, leading to pancreatic islets destruction and to the development of DM within 48 hours, with fasting blood glucose higher than 500 mg/dL.

 

Type-II Diabetes

a. Diet Induced Obesity (DIO) Models

DIO animals represent a highly useful induced model for studying NIDDM, obesity and hypercholesterolemia. In our AF, male C57 BL/6 mice or Sprague-Dawley (SD) rats are fed for 4-8 weeks with a High Fat Diet (HFD, containing more than 60% of fat) to induce obesity and obesity-related NIDDM and hypercholesterolemia.

b. Obese-Diabetic db/db mice

The db/db spontaneous mutant mouse model, carrying a homozygous loss of function mutation in the gene encoding for leptin receptor on a C57 BL/6 background, is a highly suitable model for studying NIDDM. The pathologic events start at 10 to 14 days of age with elevation of plasma insulin leading to frank diabetes at four to eight weeks of age. This model is characterized by obesity, polyphagia, polydipsia, polyuria and insulin resistance.