Effects of exercise on brain functions in diabetic animal models

Table 1 Summary of animal models of type 1 diabetes mellitus

Induction	Models	Dose(s) (mg/kg)	Main characteristics	Model uses
Chemicals	Streptozotocin	Rat 35-65 (iv or ip) Mice 100-200 (iv or ip) Hamster 50 (ip) Dog 20-30 (iv) Pig 100-150 (iv) Primates 50-150 (iv)		New formulations of insulin transplantation models
	Alloxan	Rat 40-200 (iv or ip) Mice 50-200 (iv or ip) Rabbit 100-150 (iv or ip) Dog 50-75 (iv or ip)	Hyperglycemia
	Multiple low dose Streptozotocin			Treatments prevent beta cell destructions
Spontaneous autoimmune	NOD mice BB rats LEW.1AR1/-iddm rats		Beta cell destruction due to an autoimmune process	Understanding genetics of T1DM Understanding mechanism of T1DM Treatments prevent beta cell destruction Treatments manipulate autoimmune process
Genetically induced	AKITA		Beta cell destruction due to ER stress Insulin dependent	New formulations of insulin Transplantation models Treatments to prevent ER stress
Virally-induced	Coxsakie B virus Encephalomyocarditis virus Kilham rat virus		Beta cell destruction induced by viral infection of beta cells	Establish potential role of viruses in the development of T1DM

iv: Intravenous injection; ip: Intraperitoneal injection; T1DM: Type 1 diabetes mellitus.

Table 2 Summary of animal model of Type 2 diabetes mellitus

Induction	Model	Main characteristics	Model uses
Obese models	ob/ob mice db/db mice KK mice KK/Ay mice NZO mice TSOD mice Zucker fatty rat Zucker diabetic fatty rat OLETE rat	Obesity-induced hyperglycemia	Identifying factors involved in obesity-induced diabetes Some models show diabetic complications Treatments to improve beta cell function
Non-obese models	GK rat Cohen diabetic rat	Hyperglycemia induced by insufficient beta cell function	Treatments to improve beta cell function and beta cell survival
Diet/nutrition induced obesity	High fat feeding (mice and rat) Desert gerbil Nile grass rat	Obesity-induced hyperglycemia	Treatments to improve insulin resistance Treatments to improve beta cell function Treatments to prevent diet-induced obesity
Surgical diabetic animals	VMH lesioned dietary Obese diabetic rat Partially pancreatectomized animals (dog, primate, pig and rats)	Avoid cytotoxic effects of chemical diabetogens on other body organs Resembles human T2DM due to reduced pancreatic islet beta cell mass	Occurrence of hyperphagia Pancreatitis
Transgenic/knock-out diabetic animals	Uncoupling protein (UCP1) Knock out mice HiAPP mice	Poor activation of thermogenesis Amyloid deposition in islets	Treatments of obese conditions Increase obesity (energy storage) Treatments to prevent amyloid deposition

Table 3 Exercise animal models on brain function

Exercise type	Method	Measurement	Note1	Note2
Aerobic exercise	Voluntary running wheel exercise	Freely access to running wheel Exercise strength can be measured via digital counter. The running wheel was rotated by animal effort		Cognitive performance Neurogenesis in subgranular zone or subventricular zone Improvements of learning and memory Neurophysiological development Relationship between Brain and Stress axis Feeding behavior
	Involuntary treadmill exercise	Enforced running exercise
		Regularly enforced running exercise is enforced with constant speed on a motorized treadmill
	Forced swimming	Animals are forced to swim in an acrylic glass cylinder filled with water	This test is used to see a rodent’s response to the threat of drowning whose result has been interpreted as measuring susceptibility to negative mood. It is commonly used to measure the effectiveness of antidepressants
Non-aerobic resistance exercise	Weight lifting	Kondziela's inverted screen test	The inverted screen is a 43 cm square of wire mesh consisting of 12 mm squares of 1 mm diameter wire	Cognition Neuronal plasticity changes Anti-inflammatory response in brain Neurogenesis in subgranular zone and subventricular zone
		Weights test	Seven weights constitute the apparatus Ranging from 20 to 98 g
		Grip strength test	Forelimb grip strength is accessed using a digital Grip Strength Meter

¹Principal;

²Uses.