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Mammalian models of diabetes mellitus, with a focus on type 2 diabetes mellitus

Nature Reviews Endocrinology volume 19, pages 350–360 (2023)Cite this article

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Abstract

Although no single animal model replicates all aspects of diabetes mellitus in humans, animal models are essential for the study of energy balance and metabolism control as well as to investigate the reasons for their imbalance that could eventually lead to overt metabolic diseases such as type 2 diabetes mellitus. The most frequently used animal models in diabetes mellitus research are small rodents that harbour spontaneous genetic mutations or that can be manipulated genetically or by other means to influence their nutrient metabolism and nutrient handling. Non-rodent species, including pigs, cats and dogs, are also useful models in diabetes mellitus research. This Review will outline the advantages and disadvantages of selected animal models of diabetes mellitus to build a basis for their most appropriate use in biomedical research.

Key points

  • A large number of rodent models are available to study the pathophysiology and consequences of, and treatment options for, diabetes mellitus.

  • Typically, a single rodent model does not recapitulate all the major pathophysiological aspects of type 2 diabetes mellitus (insulin resistance, disturbed β-cell function, pancreatic amyloid deposition).

  • The most frequently used large animal models include pigs, dogs and cats; most diabetic cats have a disease entity similar to human type 2 diabetes mellitus, whereas, in most diabetic dogs, the disease resembles human type 1 diabetes mellitus.

  • In any given animal model, the diabetic phenotype (for example, severity of hyperglycaemia) can differ depending on housing and feeding conditions.

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Fig. 1: Major organs involved in the control of energy metabolism and affected by dysregulated metabolism in diabetes mellitus in humans, rodents, pigs, dogs and cats.

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Acknowledgements

The author gratefully acknowledges the financial support of many funding sources, which have helped in conducting research using some of the animal models mentioned here: in particular, the Swiss National Science Foundation, the National Institutes of Health, the EU Seventh Framework Programme and the University of Zurich. The author gratefully acknowledges the help of Mrs Jeanne Peter, Vetsuisse Faculty University of Zurich, in preparing the first drafts of the display items.

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    Thomas A. Lutz

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Lutz, T.A. Mammalian models of diabetes mellitus, with a focus on type 2 diabetes mellitus. Nat Rev Endocrinol 19, 350–360 (2023). https://doi.org/10.1038/s41574-023-00818-3

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