. 2019 Aug 28;8(9):1332. doi: 10.3390/jcm8091332

Table 2.

Animal models most commonly used to study type 2 diabetes mellitus.

Induction Mechanism	Model	Main Features	Possible Uses	Advantages	Disadvantages	Ref.
Obese monogenic models	Lep^ob/ob mice (mutated leptin gene)	Obesity-induced hyperglycemia, with hyperphagic, obese, hyperinsulinaemic and hyperglycemic animals	Treatments to improve insulin resistance	Pancreatic islet volume dramatically increased	Infertile mice	[29]
					Metabolic aberrations (hyperlipidemia disturbance in temperature regulation, lower physical activity)
					Diabetes not particular severe and thus not completely representative of human T2DM
	Lepr^db/db mice (mutated leptin receptor gene)		Treatments to improve β-cell function		Ketosis after a few months of age, having a relative short lifespan	[30]
	Zucker Diabetic Fatty (ZDF) Rats (mutated leptin receptor gene)			Diabetic complications also develop	Hypertensive rats	[31]
				Diabetic complications also develop	Females do not develop overt diabetes	[31]
Obese polygenic models	KK mice	Obesity-induced hyperglycemia	Treatments to improve insulin resistance
	Otsuka Long-Evans Tokushima Fat (OLEFT) rat		Treatments to improve β-cell function	Three stages of histological changes can be observed		[32,33]
	New Zealand Obese (NZO) mice		Some models show diabetic complications	Renal complications		[32,33]
	TallyHo/Jng mice			Adiposity, plasma triglycerides, cholesterol and free fatty acid levels are increased	Only male mice develop hyperglycemia
	NoncNZO10/LtJ mice			Indicated for diabetic wound healing studies
	NoncNZO10/LtJ mice			Nephropathy presence
Induced obesity models	High fat feeding (mice or rats)	Obesity-induced hyperglycemia	Treatments to improve insulin resistance	Baboons and humans are genetically, anatomically and physiologically very similar	Handling of baboon is somewhat difficult	[31,33]
	Desert gerbil		Treatments to improve β-cell function	Cardiac complications can be studied	Veterinarian is required
	Nile grass rat		Treatments to prevent diet-induced obesity	Cardiac complications can be studied	Costly model containing
Non-obese models	Goto-Kakizaki (GK) rat	Hyperglycemia induced by insufficient β-cell function or mass	Treatments to improve β-cell function	Allow the study of β-cell function and diabetic complications	Interstrains variability of the islets morphology and metabolism	[31,33]
Non-obese models	Goto-Kakizaki (GK) rat		Treatments to improve β-cell survival			[31,33]
Genetically induced models of β-cell dysfunction	Human islet amyloid polypeptide-expressing (hIAPP) mice	Amyloid deposition in islets	Treatments to prevent amyloid deposition	Express human IAPP under the insulin promoter, which can form amyloid within the islets for further study	Transgenic mice	[31,33]
Genetically induced models of β-cell dysfunction		Amyloid deposition in islets	Treatments to improve β-cell function		Transgenic mice	[31,33]
		β-cell destruction due to ER stress	Treatments to prevent ER stress		β-cell adaption to increased insulin demand is restricted
		β-cell destruction due to ER stress	Treatments to improve β-cell survival		β-cell adaption to increased insulin demand is restricted
Non-rodent models	Cat models	Amyloid deposition in islets	Treatments to improve β-cell function	Islet amyloidosis study	More expensive models	[31,33,34,35,36,37]
	Cat models	β-cell destruction	Treatments to prevent diet-induced obesity	Islet amyloidosis study
	Old-world non-human primates			Similarities to human condition