Animal models
Our team brings extensive experience in testing a wide range of therapeutics using animal models for type 1 diabetes, e.g., in NOD mice or chemically-induced diabetes models. With a comprehensive suite of read-outs and data analysis capabilities, paired with cutting-edge facilities and technology platforms, we are equipped to conduct both proof-of-concept studies and larger, more complex experiments to evaluate innovative therapies.
NOD model
Non-obese diabetic (NOD) mice spontaneously develop type 1 diabetes. We specialize in evaluating therapeutic interventions in vivo. Our expertise spans testing therapies at various disease stages, including preventive approaches, interventions at disease onset (new-onset), and therapies for established disease. We also have experience in islet transplantation under the kidney capsule or at other sites. Despite advances in immunotherapies, some individuals with type 1 diabetes—referred to as non-responders—fail to benefit from treatment. The Leuven Diabetes Lab investigates the underlying mechanisms of therapy resistance and strives to develop predictive tools for treatment responses.
Chemically-induced models
Besides the NOD model, we use chemically-induced diabetes models, either alloxan- or streptozotocin-induced, to examine treatment effects on hyperglycemia. In both models, the beta cells in the pancreas are chemically targeted via the GLUT2-transporter, inducing hyperglycemia within days after the administration, making it faster than the NOD model. However, the autoimmune component of type 1 diabetes pathology is not represented in this model.
Disease-modifying therapies
We are skilled in examining single or combination therapies using different administration routes, such as subcutaneous, intraperitoneal, oral, and intravenous administration. In addition, our lab can perform pancreatic islet transplantations under the kidney capsule. Our services include designing complex preclinical intervention studies and optimizing treatment regimens for compounds of interest. Additionally, we bring extensive expertise in the analysis of whole blood, peripheral blood mononuclear cells (PBMCs), and tissues to support in vivo effects.
Read-outs
Our immunological read-outs include:
- Complete hematology analysis (Scil Vet abc plus)
- Blood levels of insulin autoantibodies (Enable Biosciences)
- Inflammatory analytes (Meso Scale Discovery)
- Insulitis (histology and immunofluorescence imaging)
- Multi-parameter flow cytometry
- Single-cell RNA sequencing
Our metabolic read-outs include:
- Glucose monitoring in the blood and urine
- Insulin/C-peptide measurements in the blood
- Intraperitoneal glucose tolerance test
- Intraperitoneal insulin tolerance tests