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.
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.
This is a preview of subscription content, access via your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Cooper, G. J. Amylin compared with calcitonin gene-related peptide: structure, biology, and relevance to metabolic disease. Endocr. Rev. 15, 163–201 (1994).
Rand, J. S., Fleeman, L. M., Farrow, H. A., Appleton, D. J. & Lederer, R. Canine and feline diabetes mellitus: nature or nurture? J. Nutr. 134, 2072–2080 (2004).
Huang, H. J. et al. Hyperamylinemia, hyperinsulinemia, and insulin resistance in genetically obese LA/N-cp rats. Hypertension 19, 101–109 (1992).
Osto, M. & Lutz, T. A. Translational value of animal models of obesity — focus on dogs and cats. Eur. J. Pharmacol. 759, 240–252 (2015).
Lee, Y. et al. Metabolic manifestations of insulin deficiency do not occur without glucagon action. Proc. Natl Acad. Sci. USA 109, 14972–14976 (2012).
Wang, M.-Y. et al. Glucagon receptor antibody completely suppresses type 1 diabetes phenotype without insulin by disrupting a novel diabetogenic pathway. Proc. Natl Acad. Sci. USA 112, 2503–2508 (2015).
D’Alessio, D. The role of dysregulated glucagon secretion in type 2 diabetes. Diabetes Obes. Metab. 13, 126–132 (2011).
Unger, R. H., Dobbs, R. E. & Orci, L. Insulin, glucagon, and somatostatin secretion in the regulation of metabolism. Annu. Rev. Physiol. 40, 307–343 (1978).
Deacon, C. F. & Ahrén, B. Physiology of incretins in health and disease. Rev. Diabet. Stud. 8, 293–306 (2011).
Drucker, D. J. Biologic actions and therapeutic potential of the proglucagon-derived peptides. Nat. Clin. Pract. Endocrinol. Metab. 1, 22–31 (2005).
Ahrén, B., Yamada, Y. & Seino, Y. Islet adaptation in GIP receptor knockout mice. Peptides 125, 170152 (2020).
Kleinert, M. et al. Animal models of obesity and diabetes mellitus. Nat. Rev. Endocrinol. 14, 140–162 (2018).
Lone, I. M. & Iraqi, F. A. Genetics of murine type 2 diabetes and comorbidities. Mamm. Genome 33, 421–436 (2022).
Kahn, C. R. Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes 43, 1066–1084 (1994).
Bruning, J. C. et al. Role of brain insulin receptor in control of body weight and reproduction. Science 289, 2122–2125 (2000).
Hirosumi, J. et al. A central role for JNK in obesity and insulin resistance. Nature 420, 333–336 (2002).
Boden, G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 46, 3–10 (1997).
Hotamisligil, G. S., Shargill, N. S. & Spiegelman, B. M. Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science 259, 87–91 (1993).
Hotamisligil, G. S. & Spiegelman, B. M. Tumor necrosis factor α: a key component of the obesity-diabetes link. Diabetes 43, 1271–1278 (1994).
Coleman, D. L. Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 14, 141–148 (1978).
Mayer, J., Bates, M. W. & Dickie, M. M. Hereditary diabetes in genetically obese mice. Science 113, 746–747 (1951).
O’Rahilly, S. Human genetics illuminates the paths to metabolic disease. Nature 462, 307–314 (2009).
Coleman, D. L. & Hummel, K. P. The influence of genetic background on the expression of the obese (Ob) gene in the mouse. Diabetologia 9, 287–293 (1973).
Trayhurn, P., Thurlby, P. L. & James, W. P. Thermogenic defect in pre-obese ob/ob mice. Nature 266, 60–62 (1977).
Bray, G. A. The Zucker-fatty rat: a review. Fed. Proc. 36, 148–153 (1977).
Bray, G. A. & York, D. A. Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiol. Rev. 59, 719–809 (1979).
Chua, S. C. Jr. et al. Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 271, 994–996 (1996).
Takaya, K. et al. Nonsense mutation of leptin receptor in the obese spontaneously hypertensive Koletsky rat. Nat. Genet. 14, 130–131 (1996).
Friedman, J. M. Leptin, leptin receptors and the control of body weight. Eur. J. Med. Res. 2, 7–13 (1997).
Wu-Peng, X. S. et al. Phenotype of the obese Koletsky (f) rat due to Tyr763Stop mutation in the extracellular domain of the leptin receptor (Lepr): evidence for deficient plasma-to-CSF transport of leptin in both the Zucker and Koletsky obese rat. Diabetes 46, 513–518 (1997).
Crouse, J. A. et al. Altered cell surface expression and signaling of leptin receptors containing the fatty mutation. J. Biol. Chem. 273, 18365–18373 (1998).
da Silva, B. A., Bjorbaek, C., Uotani, S. & Flier, J. S. Functional properties of leptin receptor isoforms containing the gln→pro extracellular domain mutation of the fatty rat. Endocrinology 139, 3681–3690 (1998).
Zierath, J. R. et al. Role of skeletal muscle in thiazolidinedione insulin sensitizer (PPARγ agonist) action. Endocrinology 139, 5034–5041 (1998).
Peterson, R. G., Shaw, W. N., Neel, M.-A., Little, L. A. & Eichberg, J. Zucker diabetic fatty rat as a model for non-insulin-dependent diabetes mellitus. ILAR J. 32, 16–19 (1990).
Tokuyama, Y. et al. Evolution of β-cell dysfunction in the male Zucker diabetic fatty rat. Diabetes 44, 1447–1457 (1995).
Kawano, K. et al. Spontaneous long-term hyperglycemic rat with diabetic complications. Otsuka Long-Evans Tokushima Fatty (OLETF) strain. Diabetes 41, 1422–1428 (1992).
Moran, T. H. Unraveling the obesity of OLETF rats. Physiol. Behav. 94, 71–78 (2008).
Allison, M. B. & Myers, M. G. Jr. 20 years of leptin: connecting leptin signaling to biological function. J. Endocrinol. 223, T25–T35 (2014).
Elias, C. F. et al. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 23, 775–786 (1999).
Huszar, D. et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131–141 (1997).
Levin, B. E., Dunn-Meynell, A. A., Balkan, B. & Keesey, R. E. Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats. Am. J. Physiol. 273, R725–R730 (1997).
Levin, B. E., Triscari, J. & Sullivan, A. C. Altered sympathetic activity during development of diet-induced obesity in rat. Am. J. Physiol. 244, R347–R355 (1983).
Levin, B. E., Triscari, J. & Sullivan, A. C. Metabolic features of diet-induced obesity without hyperphagia in young rats. Am. J. Physiol. 251, R433–R440 (1986).
Levin, B. E. & Dunn-Meynell, A. A. Defense of body weight against chronic caloric restriction in obesity-prone and -resistant rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 278, R231–R237 (2000).
Levin, B. E. & Dunn-Meynell, A. A. Defense of body weight depends on dietary composition and palatability in rats with diet-induced obesity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282, R46–R54 (2002).
Levin, B. E., Triscari, J. & Sullivan, A. C. The effect of diet and chronic obesity on brain catecholamine turnover in the rat. Pharmacol. Biochem. Behav. 24, 299–304 (1986).
Levin, B. E. et al. A new obesity-prone, glucose-intolerant rat strain (F.DIO). Am. J. Physiol. Regul. Integr. Comp. Physiol. 285, R1184–R1191 (2003).
Levin, B. E., Dunn-Meynell, A. A., Ricci, M. R. & Cummings, D. E. Abnormalities of leptin and ghrelin regulation in obesity-prone juvenile rats. Am. J. Physiol. Endocrinol. Metab. 285, E949–E957 (2003).
Bouret, S. G. et al. Hypothalamic neural projections are permanently disrupted in diet-induced obese rats. Cell Metab. 7, 179–185 (2008).
Gorski, J. N., Dunn-Meynell, A. A. & Levin, B. E. Maternal obesity increases hypothalamic leptin receptor expression and sensitivity in juvenile obesity-prone rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, R1782–R1791 (2007).
Marques, C. et al. High-fat diet-induced obesity rat model: a comparison between Wistar and Sprague-Dawley rat. Adipocyte 5, 11–21 (2016).
Schemmel, R., Mickelsen, O. & Gill, J. L. Dietary obesity in rats: body weight and body fat accretion in seven strains of rats. J. Nutr. 100, 1041–1048 (1970).
Parks, B. W. et al. Genetic architecture of insulin resistance in the mouse. Cell Metab. 21, 334–347 (2015).
Kahle, M. et al. Phenotypic comparison of common mouse strains developing high-fat diet-induced hepatosteatosis. Mol. Metab. 2, 435–446 (2013).
Peterson, R. G. et al. Characterization of the ZDSD rat: a translational model for the study of metabolic syndrome and type 2 diabetes. J. Diabetes Res. 2015, 487816 (2015).
Reinwald, S., Peterson, R. G., Allen, M. R. & Burr, D. B. Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models. Am. J. Physiol. Endocrinol. Metab. 296, E765–E774 (2009).
Mauvais-Jarvis, F., Arnold, A. P. & Reue, K. A guide for the design of pre-clinical studies on sex differences in metabolism. Cell Metab. 25, 1216–1230 (2017).
Clegg, D. J., Brown, L. M., Woods, S. C. & Benoit, S. C. Gonadal hormones determine sensitivity to central leptin and insulin. Diabetes 55, 978–987 (2006).
Meyer, M. R., Clegg, D. J., Prossnitz, E. R. & Barton, M. Obesity, insulin resistance and diabetes: sex differences and role of oestrogen receptors. Acta Physiol. 203, 259–269 (2011).
Shi, H., Seeley, R. J. & Clegg, D. J. Sexual differences in the control of energy homeostasis. Front. Neuroendocrinol. 30, 396–404 (2009).
Bjorntorp, P. Body fat distribution, insulin resistance, and metabolic diseases. Nutrition 13, 795–803 (1997).
Christoffersen, B., Raun, K., Svendsen, O., Fledelius, C. & Golozoubova, V. Evalution of the castrated male Sprague-Dawley rat as a model of the metabolic syndrome and type 2 diabetes. Int. J. Obes. 30, 1288–1297 (2006).
Asarian, L. & Geary, N. Sex differences in the physiology of eating. Am. J. Physiol. Regul. Integr. Comp. Physiol. 305, R1215–R1267 (2013).
Tamashiro, K. L. & Moran, T. H. Perinatal environment and its influences on metabolic programming of offspring. Physiol. Behav. 100, 560–566 (2010).
Bouret, S. G. Early life origins of obesity: role of hypothalamic programming. J. Pediatr. Gastroenterol. Nutr. 48, 31–38 (2009).
Le Foll, C., Irani, B. G., Magnan, C., Dunn-Meynell, A. & Levin, B. E. Effects of maternal genotype and diet on offspring glucose and fatty acid-sensing ventromedial hypothalamic nucleus neurons. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, R1351–R1357 (2009).
Levin, B. E. & Dunn-Meynell, A. A. Maternal obesity alters adiposity and monoamine function in genetically predisposed offspring. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283, R1087–R1093 (2002).
Levin, B. E. & Govek, E. Gestational obesity accentuates obesity in obesity-prone progeny. Am. J. Physiol. 275, R1374–R1379 (1998).
Sullivan, E. L. et al. Chronic consumption of a high-fat diet during pregnancy causes perturbations in the serotonergic system and increased anxiety-like behavior in nonhuman primate offspring. J. Neurosci. 30, 3826–3830 (2010).
Sullivan, E. L., Smith, M. S. & Grove, K. L. Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood. Neuroendocrinology 93, 1–8 (2010).
Tamashiro, K. L., Terrillion, C. E., Hyun, J., Koenig, J. I. & Moran, T. H. Prenatal stress or high-fat diet increases susceptibility to diet-induced obesity in rat offspring. Diabetes 58, 1116–1125 (2009).
West, D. B., Diaz, J. & Woods, S. C. Infant gastrostomy and chronic formula infusion as a technique to overfeed and accelerate weight gain of neonatal rats. J. Nutr. 112, 1339–1343 (1982).
Leuthardt, A. S., Bayer, J., Monné Rodríguez, J. M. & Boyle, C. N. Influence of high energy diet and polygenic predisposition for obesity on postpartum health in rat dams. Front. Physiol. 12, 772707 (2021).
Gurlo, T. et al. Pregnancy in human IAPP transgenic mice recapitulates beta cell stress in type 2 diabetes. Diabetologia 62, 1000–1010 (2019).
Faust, I. M., Johnson, P. R. & Hirsch, J. Long-term effects of early nutritional experience on the development of obesity in the rat. J. Nutr. 110, 2027–2034 (1980).
Schmidt, I. et al. The effect of leptin treatment on the development of obesity in overfed suckling Wistar rats. Int. J. Obes. Relat. Metab. Disord. 25, 1168–1174 (2001).
Morris, M. J., Velkoska, E. & Cole, T. J. Central and peripheral contributions to obesity-associated hypertension: impact of early overnourishment. Exp. Physiol. 90, 697–702 (2005).
West, D. B., Diaz, J., Roddy, S. & Woods, S. C. Long-term effects on adiposity after preweaning nutritional manipulations in the gastrostomy-reared rat. J. Nutr. 117, 1259–1264 (1987).
Asarian, L. & Geary, N. Cyclic estradiol treatment normalizes body weight and restores physiological patterns of spontaneous feeding and sexual receptivity in ovariectomized rats. Horm. Behav. 42, 461–471 (2002).
Thammacharoen, S., Lutz, T. A., Geary, N. & Asarian, L. Hindbrain administration of estradiol inhibits feeding and activates estrogen receptor-alpha-expressing cells in the nucleus tractus solitarius of ovariectomized rats. Endocrinology 149, 1609–1617 (2008).
Asarian, L. & Geary, N. Estradiol enhances cholecystokinin-dependent lipid-induced satiation and activates estrogen receptor-alpha-expressing cells in the nucleus tractus solitarius of ovariectomized rats. Endocrinology 148, 5656–5666 (2007).
Asarian, L. & Geary, N. Modulation of appetite by gonadal steroid hormones. Philos. Trans. R. Soc. Lond. B Biol. Sci. 361, 1251–1263 (2006).
Asarian, L. et al. Estradiol increases body-weight loss and gut-peptide satiation after Roux-en-Y gastric bypass in ovariectomized rats. Gastroenterology 143, 325–327 (2012).
Akash, M. S., Rehman, K. & Chen, S. Goto-Kakizaki rats: its suitability as non-obese diabetic animal model for spontaneous type 2 diabetes mellitus. Curr. Diabetes Rev. 9, 387–396 (2013).
Yoshioka, M., Kayo, T., Ikeda, T. & Koizumi, A. A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice. Diabetes 46, 887–894 (1997).
Kalaitzoglou, E., Fowlkes, J. L. & Thrailkill, K. M. Mouse models of type 1 diabetes and their use in skeletal research. Curr. Opin. Endocrinol. Diabetes Obes. 29, 318–325 (2022).
Reed, M. J. et al. A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism 49, 1390–1394 (2000).
Westermark, P., Andersson, A. & Westermark, G. T. Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. Physiol. Rev. 91, 795–826 (2011).
Westermark, P., Wernstedt, C., Wilander, E. & Sletten, K. A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas. Biochem. Biophys. Res. Commun. 140, 827–831 (1986).
Clark, A. et al. Islet amyloid formed from diabetes-associated peptide may be pathogenic in type-2 diabetes. Lancet 2, 231–234 (1987).
Cooper, G. J. et al. Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients. Proc. Natl Acad. Sci. USA 84, 8628–8632 (1987).
Lutz, T. A. Creating the amylin story. Appetite 172, 105965 (2022).
Johnson, K. H., Hayden, D. W., O’Brien, T. D. & Westermark, P. Spontaneous diabetes mellitus-islet amyloid complex in adult cats. Am. J. Pathol. 125, 416–419 (1986).
Johnson, K. H. & Stevens, J. B. Light and electron microscopic studies of islet amyloid in diabetic cats. Diabetes 22, 81–90 (1973).
O’Brien, T. D., Butler, P. C., Westermark, P. & Johnson, K. H. Islet amyloid polypeptide: a review of its biology and potential roles in the pathogenesis of diabetes mellitus. Vet. Pathol. 30, 317–332 (1993).
Westermark, G. T., Krogvold, L., Dahl-Jørgensen, K. & Ludvigsson, J. Islet amyloid in recent-onset type 1 diabetes-the DiViD study. Ups. J. Med. Sci. 122, 201–203 (2017).
Denroche, H. C. & Verchere, C. B. IAPP and type 1 diabetes: implications for immunity, metabolism and islet transplants. J. Mol. Endocrinol. 60, R57–R75 (2018).
Le Foll, C. & Lutz, T. A. Systemic and central amylin, amylin receptor signaling, and their physiological and pathophysiological roles in metabolism. Compr. Physiol. 10, 811–837 (2020).
Hay, D. L., Chen, S., Lutz, T. A., Parkes, D. G. & Roth, J. D. Amylin: pharmacology, physiology, and clinical potential. Pharmacol. Rev. 67, 564–600 (2015).
O’Brien, T. D., Hayden, D. W., Johnson, K. H. & Fletcher, T. F. Immunohistochemical morphometry of pancreatic endocrine cells in diabetic, normoglycaemic glucose-intolerant and normal cats. J. Comp. Pathol. 96, 357–369 (1986).
Johnson, K. H. et al. Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques. Am. J. Pathol. 130, 1–8 (1988).
Despa, F. & Goldstein, L. B. Amylin dyshomeostasis hypothesis: small vessel-type ischemic stroke in the setting of type-2 diabetes. Stroke 52, e244–e249 (2021).
Despa, S. et al. Hyperamylinemia contributes to cardiac dysfunction in obesity and diabetes: a study in humans and rats. Circ. Res. 110, 598–608 (2012).
Despa, S. et al. Cardioprotection by controlling hyperamylinemia in a “humanized” diabetic rat model. J. Am. Heart Assoc. 3, e001015 (2014).
Verma, N. et al. Diabetic microcirculatory disturbances and pathologic erythropoiesis are provoked by deposition of amyloid-forming amylin in red blood cells and capillaries. Kidney Int. 97, 143–155 (2020).
Lorenzo, A., Razzaboni, B., Weir, G. C. & Yankner, B. A. Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus. Nature 368, 756–760 (1994).
Donath, M. Y. When metabolism met immunology. Nat. Immunol. 14, 421–422 (2013).
Meier, D. T. et al. Islet amyloid formation is an important determinant for inducing islet inflammation in high-fat-fed human IAPP transgenic mice. Diabetologia 57, 1884–1888 (2014).
Raleigh, D., Zhang, X., Hastoy, B. & Clark, A. The β-cell assassin: IAPP cytotoxicity. J. Mol. Endocrinol. 59, R121–R140 (2017).
Butler, A. E. et al. Diabetes due to a progressive defect in β-cell mass in rats transgenic for human islet amyloid polypeptide (HIP Rat): a new model for type 2 diabetes. Diabetes 53, 1509–1516 (2004).
Matveyenko, A. V. & Butler, P. C. Islet amyloid polypeptide (IAPP) transgenic rodents as models for type 2 diabetes. ILAR J. 47, 225–233 (2006).
Hiddinga, H. J. et al. Expression of wild-type and mutant S20G hIAPP in physiologic knock-in mouse models fails to induce islet amyloid formation, but induces mild glucose intolerance. J. Diabetes Investig. 3, 138–147 (2012).
Templin, A. T. et al. Low concentration IL-1β promotes islet amyloid formation by increasing hIAPP release from humanised mouse islets in vitro. Diabetologia 63, 2385–2395 (2020).
Blencowe, M. et al. IAPP-induced beta cell stress recapitulates the islet transcriptome in type 2 diabetes. Diabetologia 65, 173–187 (2022).
Hull, R. L. et al. Increased dietary fat promotes islet amyloid formation and β-cell secretory dysfunction in a transgenic mouse model of islet amyloid. Diabetes 52, 372–379 (2003).
Guardado-Mendoza, R. et al. Pancreatic islet amyloidosis, β-cell apoptosis, and α-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons. Proc. Natl Acad. Sci. USA 106, 13992–13997 (2009).
Renner, S. et al. Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research. Theriogenology 86, 406–421 (2016).
Pound, L. D., Kievit, P. & Grove, K. L. The nonhuman primate as a model for type 2 diabetes. Curr. Opin. Endocrinol. Diabetes Obes. 21, 89–94 (2014).
Renner, S. et al. Porcine models for studying complications and organ crosstalk in diabetes mellitus. Cell Tissue Res. 380, 341–378 (2020).
Renner, S. et al. Glucose intolerance and reduced proliferation of pancreatic beta-cells in transgenic pigs with impaired glucose-dependent insulinotropic polypeptide function. Diabetes 59, 1228–1238 (2010).
Umeyama, K. et al. Dominant-negative mutant hepatocyte nuclear factor 1alpha induces diabetes in transgenic-cloned pigs. Transgenic Res. 18, 697–706 (2009).
Renner, S. et al. Permanent neonatal diabetes in INS(C94Y) transgenic pigs. Diabetes 62, 1505–1511 (2013).
Lutz, T. A. & Rand, J. S. Pathogenesis of feline diabetes mellitus. Vet. Clin. North Am. Small Anim. Pract. 25, 527–552 (1995).
Martin, L. J. et al. Acute hormonal response to glucose, lipids and arginine infusion in overweight cats. J. Nutr. Sci. 3, e8 (2014).
Henson, M. S. & O’Brien, T. D. Feline models of type 2 diabetes mellitus. ILAR J. 47, 234–242 (2006).
Zini, E. et al. Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat. Diabetologia 52, 336–346 (2009).
Lutz, T. A., Ainscow, J. & Rand, J. S. Frequency of pancreatic amyloid deposition in cats from south-eastern Queensland. Aust. Vet. J. 71, 254–256 (1994).
Lutz, T. A. & Rand, J. S. Detection of amyloid deposition in various regions of the feline pancreas by different staining techniques. J. Comp. Pathol. 116, 157–170 (1997).
Yano, B. L., Hayden, D. W. & Johnson, K. H. Feline insular amyloid: association with diabetes mellitus. Vet. Pathol. 18, 621–627 (1981).
Yano, B. L., Hayden, D. W. & Johnson, K. H. Feline insular amyloid: incidence in adult cats with no clinicopathologic evidence of overt diabetes mellitus. Vet. Pathol. 18, 310–315 (1981).
Zini, E. et al. Endocrine pancreas in cats with diabetes mellitus. Vet. Pathol. 53, 136–144 (2016).
Nelson, R. W. & Reusch, C. E. Animal models of disease: classification and etiology of diabetes in dogs and cats. J. Endocrinol. 222, T1–T9 (2014).
Ionut, V. et al. Novel canine models of obese prediabetes and mild type 2 diabetes. Am. J. Physiol. Endocrinol. Metab. 298, E38–E48 (2010).
Zheng, D., Ionut, V., Mooradian, V., Stefanovski, D. & Bergman, R. N. Portal glucose infusion-glucose clamp measures hepatic influence on postprandial systemic glucose appearance as well as whole body glucose disposal. Am. J. Physiol. Endocrinol. Metab. 298, E346–E353 (2010).
Roesti, E. S. et al. Vaccination against amyloidogenic aggregates in pancreatic islets prevents development of type 2 diabetes mellitus. Vaccines 8, 116 (2020).
Ahlqvist, E. et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 6, 361-369 https://doi.org/10.1016/s2213-8587(18)30051-2 (2018).
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.
The author declares no competing interests.
Peer review information
Nature Reviews Endocrinology thanks Eckhard Wolf, Stephen O’Rahilly and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
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