In Vivo Models for Type 1 Diabetes Studies

Charles River offers validated type 1 diabetes models to support your diabetes research. Streptozotocin-induced (STZ) diabetes in rats and mice, and the NOD Mouse model of autoimmune diabetes. These animal models can be used to investigate a number of therapeutic approaches for the treatment of Type 1 diabetes.

  • Streptozotocin-induced (STZ) Rat Model
  • Multiple Low-Dose STZ Mouse Model
  • NOD Mouse Model

These type 1 rodent diabetes models are well suited for assessing drug candidates in acute or chronic experimental designs. Typical assessments include oral glucose tolerance test, estimation of beta cell/islet health and regeneration, and drug target-engagement biomarkers, as well as advanced histological endpoint.

Charles River also offers NASH models, Diet-Induced Obesity and complication Models, Glucose Tolerance Testing, and Dyslipidemia and Atherosclerosis Models to support your cardiovascular/metabolic research.

Streptozotocin-induced (STZ) Rat Model

The use of streptozotocin (STZ) in rodents to induce a type 1 diabetic phenotype has been employed in diabetes research for decades. Streptozotocin (STZ) targets and destroys pancreatic beta cells. While it can be used in a wide range of dosing patterns that can result in a continuum of diabetic phenotypes it is most commonly used to ablate pancreatic islets to induce absolute insulin dependency. The degree of hyperglycemia can be manipulated by tittering daily doses of insulin, so that animals can be maintained in a somewhat controlled hyperglycemic state for long periods of time.

Our research team has a great deal of experience with the Streptozotocin-induced (STZ) Rat Model and are experts in a wide range of STZ dosing patterns. Partnering with Charles River, our scientists can help guide your drug discovery efforts accordingly to the appropriate strategy. Discovery Services is also supported by the world’s largest group of certified veterinary pathologists, who have years of experience with pancreatic-specific histology endpoints.

  • STZ Rat Validation Data

    Streptozotocin-Induced Diabetes in Rats

    • Can be applied to almost any strain of rat.
    • Selective destruction of pancreatic beta cells.
    • Animals become extremely diabetic and insulin dependent.
    • Can titrate insulin treatment to maintain elevated blood glucose levels for an extended period of time.

     

    Glucose Tolerance in STZ-Treated SD Rats – 8 Weeks

    Line graph showing Glucose Tolerance in STZ-Treeated SD Rats at 8 Weeks. The data shows that the Control or STZ treated rats were fasted overnight prior to receiving an oral glucose challenge of 2g/kg. Blood glucose was measured at the indicated time points.
    Control or STZ treated rats were fasted overnight prior to receiving an oral glucose challenge of 2g/kg.
    Blood glucose was measured at the indicated time points.

     

    Glycosylated Hb in STZ-Treated SD Rats

    Bar graph showing Glycosylated Hb in STZ-Treated SD Rats. The data shows that STZ-Treated SD Rats Exhibit Elevations in HbA1c at 8wks post-induction of diabetes.
    STZ-Treated SD Rats Exhibit Elevations in HbA1c at 8wks post-induction of diabetes.

Multiple Low Dose Streptozotocin (MLDS) in Mice

Injection of multiple, sub-diabetogenic doses of STZ to mice results in pancreatic insulitis that progresses to near complete destruction of beta cells and a Type 1 Diabetes phenotype. This approach can be applied to any strain of mouse, including immunodeficient strains. This provides an excellent model for the assessment of cell replacement therapy for T1D.

  • MLDS Mice Validation Data

    Multiple Low Dose Streptozotocin in Mice (MLDS)

    • Injection of sub-diabetogenic doses of STZ over 5 days.
    • Minimizes impact of destroying beta cells all at once while still producing robust diabetes.
    • Blood glucose levels rise over time.

     

    Non-Fasted Blood Glucose Levels in Streptozotocin Treated C57BL/6 Mice

    Line graph showing Non-Fasted Blood Glucose Levels in Streptozotocin Treated C57BL/6 Mice. Data is showing that the Sub-diabetogenic doses of STZ were administered to C57BL/6 mice for 5 consecutive days.
    Sub-diabetogenic doses [mg/dL] of STZ were administered to C57BL/6 mice for 5 consecutive days.

NOD Mice (Autoimmune Type 1 Diabetes Model)

NOD mice are an inbred, genetically well-characterized mouse strain. Female mice have a propensity to develop T1D via an autoimmune pathway, making them particularly useful for dissecting the immunologic aspects and the role of immune tolerance in the development of T1D.

  • NOD Mouse Model Validation Data

    NOD Mice (Autoimmune Type 1 Diabetes Model)

    • Autoimmune disorder characterized by immune attack on pancreatic beta cells and insulinopenia.
    • Histopathology reveals severe insulitis. Histopathology scoring can be used to assess severity of disease.
    • Develops spontaneously over time with a much higher incidence in female animals compared to males.
    • Immune tolerance can inhibit development of diabetes in NOD mice.

     

    Incidence of spontaneous development of diabetes in male and female NOD mice.

    Scatter plot line graph showing the incidence of spontaneous development of diabetes in male and female NOD mice. The data is showing the incidence of diabetes in male vs. female per week.

    Scatter plot line graph showing the incidence of spontaneous development of diabetes in male and female NOD mice and it shows the incidence of diabetes in the insulin treated mouse vs. the untreated NOD mouse model.

    Intranasal Administration of Insulin Promotes Immune Tolerance in NOD Mice and Suppresses Development of Diabetes. Intranasal treatment with insulin to female NOD mice beginning at 6 weeks of age effectively inhibits the development of diabetes.

     

    Development of type 1 diabetes in the NOD mouse model

    Line graph showing the Development of Type 1 diabetes in the NOD mouse model and the blood glucose levels (mmol/l).

    Line graph showing the Development of Type 1 diabetes in the NOD mouse model and the incidence of hyperglycaemia (%) over a 20-week period.

    On the left is the blood glucose levels (mmol/L). The right is showing the incidence of hyperglycemia (%) over a 20-week period.

All of our Type 1 diabetes models are validated to support your type 1 diabetes research and can be used to provide a rich dataset to assess the efficacy of novel therapies for diabetes. Charles River also offers multiple models to support your Cardiovascular/Metabolic research, including NASH models, Diet-Induced Obesity and complication Models, Glucose Tolerance Testing, and Dyslipidemia and Atherosclerosis Models.

 

Contact a Diabetes Expert

 

Frequently Asked Questions (FAQs) for Type 1 Diabetes Models

  • What are the different types of type 1 diabetes study models that Charles River provides?

    Charles River provides multiple type 1 diabetes models to support your metabolic research. We offer models of chemically induced beta cell depletion (STZ-treated rats or mice) and a model for interrogating the role of immune tolerance (NOD mouse).

    Our Type 1 diabetes models rely on chemical ablation of insulin producing, pancreatic b cells. This can be accomplished with a single injection of either streptozotocin or alloxan in rats, or multiple, sub-diabetogenic doses of streptozotocin in mice. Female NOD mice develop autoimmune diabetes spontaneously over time. Type 1 diabetes has also been established in larger species such as the dog and pig. Some primate colonies maintain animals with various degrees of spontaneously occurring metabolic dysfunction also exist.

  • What are some important considerations in choosing a model system to study diabetes?

    Animal models seldom are faithful reproductions of human diseases, but they have proven to be very useful in studying the pathways and mechanisms of those diseases. With this in mind, the selection of an animal model system must consider the target or mechanism under investigation. Assessment of treatments for T1D can be very straightforward (e.g. determining efficacy of new insulin preparations or insulin sensitizers), or very complex (cell replacement therapies) depending upon the target. Biologic therapies also have the added burden of recognizing the paralogous rodent target without generating an immune response.

  • What are some commonly used animal models for studying type 1 diabetes?

    Charles River provides both type 2 and type 1 diabetes models in rodents and mice to support your metabolic research. We offer the following models:

    • NOD Mouse Model
    • Streptozotocin-induced (STZ) Rat Model

    Our type 1 diabetes study systems include chemical ablation of pancreatic beta cells and autoimmune attack and induction of insulitis for type 1 diabetes and the use of genetic mutations in mice and rats for type 2 diabetes studies. Fee­ding high fat diets to C57BL/6 mice is also an approach for studying the prediabetic condition.   

  • What end points are used to evaluate efficacy of test articles in diabetes animal models?

    Multiple considerations should be given when it comes to the selection of end points used to evaluate efficacy in the diabetes model. It is important that the selection of markers used to test efficacy relate to the mechanism of action.

    The most important end point to consider is assessing coverage of the target with a pharmacodynamic marker that is relative to the drug blood levels. This allows you to link the dose of the test article and the achieved peripheral exposure to coverage of the target under investigation All of these data gathered from your in vivo diabetes study are critical to interpret results for your research.

  • What markers are routinely used in in vivo diabetes animal studies?

    Several markers of glycemic control are routinely used in our type 1 diabetes models. These markers include:

    • Fasting and non-fasting blood glucose levels
    • Serum insulin concentration
    • Tolerance tests to assess glucose disposal, insulin sensitivity, and hepatic glucose output
    • Food intake
    • Body composition
    • Immunologic end points

    Standard clinical chemistry, histology and additional target related biomarker assessments should also be included.

    Estimation of glycosylated hemoglobin (HbA1c) tends to be less informative. Glycosylated hemoglobin remains in the circulation for the life of the affected red cell. We have observed very little change in this marker in studies conducted in the range of 14 – 28 days.