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Published on: November 29, 2024
Experimental Models to Study Diabetes Mellitus and Its Complications: Limitations and New Opportunities
Beatriz Martín-Carro1,2, Javier Donate-Correa2,3, Sara Fernández-Villabrille1,2
1Bone and Mineral Research Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.
Abstract:
Preclinical biomedical models are a fundamental tool to improve the knowledge and management of diseases, particularly in diabetes mellitus (DM) since, currently, the pathophysiological and molecular mechanisms involved in its development are not fully clarified, and there is no treatment to cure DM. This review will focus on the features, advantages and limitations of some of the most used DM models in rats, such as the spontaneous models: Bio-Breeding Diabetes-Prone (BB-DP) and LEW.1AR1-iddm, as representative models of type 1 DM (DM-1); the Zucker diabetic fatty (ZDF) and Goto-kakizaki (GK) rats, as representative models of type 2 DM (DM-2); and other models induced by surgical, dietary and pharmacological-alloxan and streptozotocin-procedures. Given the variety of DM models in rats, as well as the non-uniformity in the protocols and the absence of all the manifestation of the long-term multifactorial complications of DM in humans, the researchers must choose the one that best suits the final objectives of the study. These circumstances, added to the fact that most of the experimental research in the literature is focused on the study of the early phase of DM, makes it necessary to develop long-term studies closer to DM in humans. In this review, a recently published rat DM model induced by streptozotocin injection with chronic exogenous administration of insulin to reduce hyperglycaemia has also been included in an attempt to mimic the chronic phase of DM in humans.
Insights
This review examines preclinical rat models for diabetes mellitus (DM), highlighting their utility and limitations in understanding disease mechanisms. It emphasizes selecting appropriate models for research objectives and developing long-term studies to better reflect human diabetes complications.
Area of Science:
- Preclinical research
- Endocrinology
- Diabetology
Background:
- Preclinical biomedical models are crucial for advancing disease knowledge, especially for diabetes mellitus (DM), where underlying mechanisms and cures remain elusive.
- Current research often focuses on early-stage DM, necessitating models that better represent the chronic, multifactorial nature of human diabetes.
Purpose of the Study:
- To review the features, advantages, and limitations of commonly used rat models for diabetes mellitus (DM).
- To guide researchers in selecting the most suitable DM model based on study objectives.
- To highlight the need for long-term studies that more accurately mimic human diabetes progression and complications.
Main Methods:
- Review of spontaneous rat models for type 1 DM (Bio-Breeding Diabetes-Prone, LEW.1AR1-iddm).
- Review of spontaneous rat models for type 2 DM (Zucker diabetic fatty, Goto-kakizaki).
- Review of induced DM models (surgical, dietary, pharmacological - alloxan, streptozotocin) including a novel streptozotocin-induced model with insulin treatment to mimic chronic DM.
Main Results:
- Various rat models exist for both type 1 and type 2 diabetes mellitus, each with specific characteristics.
- Existing models present limitations, including non-uniform protocols and incomplete representation of long-term human diabetes complications.
- A recently developed streptozotocin-induced model with chronic insulin administration shows promise for studying the chronic phase of DM.
Conclusions:
- The selection of an appropriate preclinical diabetes mellitus model is critical and depends on the specific research goals.
- There is a significant need for the development and utilization of long-term preclinical studies that better recapitulate the complexity of human diabetes.
- Continued refinement of existing models and development of new ones are essential for advancing diabetes mellitus research.
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