Metabolic disorder models
Metabolic diseases represent a growing health burden to society. At Sygnature, our strong history of performing high quality in vivo pharmacology investigations (formerly under the name RenaSci) in the growing metabolic space ranging from insulin resistance to diabetic complications means we are well equipped to guide the right choice of translatable models and necessary endpoints.
We have hands-on experience with most established genetic, surgical, and dietary- or chemically-induced models of Metabolic Disorders including:
- In mouse: lean, DIO, ob/ob, db/db, STZ/HFD and more
- In rat: lean, weight-gain, glucocorticoid-induced insulin resistance, DIO, ZDF, STZ/HFD and more
The table summarizes main characteristics of Metabolic models:
| Therapeutic Indication | Models | Characteristics |
| Obesity | Normal / lean mice and rats | Non-obese, insulin sensitive |
| Dietary-induced obese (DIO) mice and rats | Excess adiposity, moderate insulin resistance, steatosis | |
| Insulin resistance | Glucocorticoid-induced insulin resistance | Insulin resistance, non-obese, rapid onset |
| Dietary-induced obese (DIO) mice and rats | Moderate insulin resistance, excess adiposity, steatosis | |
| ob/ob mouse model | Severe insulin resistance, excess adiposity, hyperphagia | |
| Type I diabetes | Streptozotocin (STZ) high fat diet (HFD) model | Insulin deficiency, hyperglycaemia, nephropathy, neuropathy |
| Type II diabetes | db/db mouse model | Progressive diabetes, hyperphagia, hyperglycaemia, insulin resistance, neuropathy, nephropathy |
| ZDF rat model |
The study design elements for assessing novel drug potential include:
- Effects of acute or chronic dosing via several routes (po, sc, ip, iv, icv)
- Anorexigenic and weight loss effects
- Energy expenditure with simultaneous assessment of locomotor activity and food intake
- Body composition including adiposity, lean mass, water retention, bone mineral density
- Behavioural aspects of feeding
- Glucose and insulin tolerance (OGTT, IPGTT, IVGTT, ITT)
- Rate of gastric emptying
- Blood, plasma, urine, and tissue biomarkers of efficacy (such as blood HbA1c and liver triglycerides)
- Hargreaves and von Frey test of neuropathy
- Drug exposure