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Type 1 diabetes T1DM animal model

Type 1 diabetes T1DM animal model

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Type 1 diabetes
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Model Introduction

Model Introduction

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Type 1 diabetes

Introduction to T1DM Animal Models

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia and is generally incurable, requiring lifelong pharmacological management. Consequently, the development of new antidiabetic therapies remains a significant challenge. Animal models of diabetes are essential for elucidating the pathogenic mechanisms of the disease and evaluating novel therapeutic agents. Establishing appropriate animal models is crucial for investigating the pathogenesis, treatment, and prevention of diabetes and its complications.

Type 1 diabetes mellitus (T1DM), formerly known as insulin-dependent diabetes mellitus (IDDM), accounts for less than 10% of all cases of diabetes. It is characterized by the destruction of pancreatic β cells, leading to reduced insulin secretion (absolute insulin deficiency) and resulting in metabolic disturbances involving carbohydrates, lipids, proteins, and other substrates.

 

 

Image source: National Library of Medicine

Various methods can be used to establish animal models of type 1 diabetes, with chemically induced diabetic models being the most widely employed.

Chemically induced diabetes models are typically established 5–7 days prior to the start of the experiment to ensure stable hyperglycemia. Two compounds, streptozotocin (STZ) and alloxan (ALX), are used to induce diabetes.

Advantages of Aniphe BioLab’s T1DM Animal Model Platform Services

Our platform boasts mature technology for establishing type 1 diabetes (T1DM) models and standardized quality-control protocols, enabling us to undertake a wide range of experimental and R&D projects.

Comprehensive model coverage

Classic modeling protocol

Animal models are commonly established by single or multiple administrations of streptozotocin, which reliably damages pancreatic β cells and yields a phenotype that closely resembles human type 1 diabetes.

Standardization of the modeling process

Model metrics are stable.

It exhibits prominent features such as sustained hyperglycemia and reduced insulin secretion, with a high modeling success rate and minimal intergroup variability.

Multidimensional Evaluation System

Standardized Feeding Monitoring

Animals are housed under SPF conditions, with regular monitoring of physiological parameters such as blood glucose, body weight, and water intake; all data are fully traceable.

Adaptable to multi-cycle studies

Comprehensive testing items

It can perform multi-dimensional assays, including biochemical analyses, pancreatic islet histopathology, immunological assessments, and molecular-level measurements.

Standardization of Data Delivery

The solution is flexible and customizable.

The dosage and observation period can be adjusted according to experimental requirements, making it suitable for various study designs.

Standardization of Data Delivery

End-to-end one-stop service

From model establishment and observation to sample analysis, the entire closed-loop process is completed, meeting the requirements for basic research and preclinical submissions.

Modeling cycle

The duration varies depending on the induction method.

1  Laboratory animals

Select the appropriate strain based on the induction method.

1  Positive drug

Commonly used positive‑acting medications, such as insulin and gliclazide, can effectively lower blood glucose levels and supplement insulin secretion.

1  Application areas

This model primarily investigates the mechanisms underlying pancreatic β-cell destruction, autoimmune injury, and diabetes‑associated multiorgan complications. It is employed for the screening of insulin formulations, islet‑protective agents, and antidiabetic drugs, as well as for evaluating their efficacy and safety. Additionally, it supports validation of drug targets and the development of novel dosage forms, making it well suited for preclinical studies such as basic biomedical research and Investigational New Drug (IND) submissions.

Different Methods for Establishing T1DM Animal Models

Streptozotocin-induced method

Streptozotocin (STZ), also known as streptozotocin, streptozotocin, or streptozotocin, contains a nitroso‑urea moiety in its structure that exerts cytotoxic effects, while its deoxyglucose moiety facilitates its uptake into pancreatic β cells. STZ selectively damages pancreatic β cells via free radicals, leading to insulin deficiency and inducing diabetes in animals.

The streptozotocin‑induced diabetic animal model closely resembles human type 1 diabetes and is currently the most widely used diabetic animal model both domestically and internationally.

 

 

Schematic diagram of the mechanism by which STZ destroys pancreatic β cells.

Modeling method:

1. Prior to model induction, male Wistar rats weighing 180–220 g were fasted for 12–16 hours but allowed free access to water.

2. A single intraperitoneal injection of STZ was administered; animals in the control group received an equivalent volume of citrate buffer via intraperitoneal injection.

3. Forty-eight or seventy-two hours after STZ injection, measure urinary glucose daily at the same time for three consecutive days using urine glucose test strips, and determine blood glucose levels by the glucose oxidase method. Urinary glucose should be ≥3+, and blood glucose should show a sustained increase. One week after STZ injection, rats exhibit polydipsia, polyphagia, polyuria, and significant weight loss; re‑testing reveals urinary glucose ≥3+, with fasting blood glucose of 11.1 mmol/L and random blood glucose of 16.7 mmol/L, at which point the animals can be designated as a diabetic model. For those that do not develop diabetes, a second STZ injection may be administered following a period of fasting.

 

 

Changes in body weight (A) and blood glucose (B) between the DM group and the CON group of rats

Alloxan-induced method

Alloxan is a β-cell–toxic agent that induces diabetes by generating superoxide radicals, which damage β cells and reduce insulin secretion. The alloxan‑induced diabetic model closely resembles human type 1 diabetes; the modeling procedure is straightforward, and the success rate is high.

Modeling method:

1. After 12 hours of fasting, rats were administered streptozotocin via the tail vein or sublingual vein; 18 hours later, they developed persistent hyperglycemia accompanied by polydipsia and polyuria. Subsequently, in the animal model, fasting blood glucose reached 11.1 mmol/L, and random blood glucose reached 16.7 mmol/L. Following two weeks of stabilization, the animals can be used as a diabetic model.

2. Alternatively, after a 12-hour fast, freshly prepared alloxan is administered by intraperitoneal injection; on the second day, rats are fasted for 12 hours prior to another intraperitoneal injection of alloxan. This method yields a high success rate in establishing the model. (Administering 25% glucose by gavage 6 hours after alloxan injection can reduce animal mortality.)

Spontaneous model

NOD mice, BB rats, and LEW-IDDM rats are the most commonly used spontaneous models of type 1 diabetes. Among these, NOD mice continue to dominate as the primary spontaneous model.

NOD mice

Diabetes in NOD/ShiLtJ mice is characterized by leukocytic infiltration of the pancreatic islets, resulting in insulitis. A hallmark of disease onset is a non-fasting blood glucose level exceeding 13.9 mmol/L.

The primary reason for the NOD mouse’s susceptibility to diabetes is its unique MHC haplotype (H2g7 = Kd, Aad, Abg7, Enull, Db). In addition, NOD mice exhibit a variety of abnormal immune phenotypes, including defects in antigen-presenting cell–mediated immune regulation, impaired T‑cell repertoire maintenance, impaired NK‑cell function, defective macrophage cytokine production and impaired wound healing, deficiency of complement component C5, and severe hearing impairment.

NOD/ShiLtJ female mice are more widely used than males because they develop IDDM symptoms earlier and at a higher incidence; by 12 weeks of age, pancreatic insulin levels are typically markedly reduced, whereas in males this phenomenon occurs several weeks later.

Furthermore, since β-cell damage in NOD/ShiLtJ mice is secondary to an autoimmune process, the course of individual immune responses is influenced by both genetic variability and environmental factors. Consequently, the susceptibility of these mice to IDDM (insulin-dependent diabetes mellitus) is also modulated, leading to an unstable incidence rate in NOD mice.

BB rat

BB rats are derived from inbred Wistar rats. The incidence of the disease is similar in males and females. Approximately 90% of the rats develop diabetes between 8 and 16 weeks of age. The diabetic phenotype is quite severe, and the rats require insulin therapy to survive.

LEW-IDDM rats

LEW-IDDM rats: These rats develop spontaneously within a genetically homogeneous Lewis rat population sharing the same MHC haplotype. They exhibit insulitis and manifest overt diabetes at approximately 8–9 weeks of age. The incidence of diabetes is around 60%, with equal rates in both males and females. Compared with NOD mice and BB rats, LEW-IDDM rats do not develop other autoimmune diseases and survive well after the onset of overt diabetes, making them suitable for studying diabetic complications.