Animal models of diabetic retinopathy: doors to investigate pathogenesis and potential therapeutics

Jo, Dong Hyun,Cho, Chang Sik,Kim, Jin Hyoung,Jun, Hyoung Oh,Kim, Jeong Hun BioMed Central 2013 Journal of biomedical science Vol.20 No.1

<P>Effective and validated animal models are valuable to investigate the pathogenesis and potential therapeutics for human diseases. There is much concern for diabetic retinopathy (DR) in that it affects substantial number of working population all around the world, resulting in visual deterioration and social deprivation. In this review, we discuss animal models of DR based on different species of animals from zebrafish to monkeys and prerequisites for animal models. Despite criticisms on imprudent use of laboratory animals, we hope that animal models of DR will be appropriately utilized to deepen our understanding on the pathogenesis of DR and to support our struggle to find novel therapeutics against catastrophic visual loss from DR.</P>

Pattern of Stress-Induced Hyperglycemia according to Type of Diabetes: A Predator Stress Model

장진선,유영혜,박신영,김지운,김헌성,윤건호,조재형 대한당뇨병학회 2013 Diabetes and Metabolism Journal Vol.37 No.6

Background: We aimed to quantify stress-induced hyperglycemia and differentiate the glucose response between normal animals and those with diabetes. We also examined the pattern in glucose fluctuation induced by stress according to type of diabetes. Methods: To load psychological stress on animal models, we used a predator stress model by exposing rats to a cat for 60 minutes and measured glucose level from the beginning to the end of the test to monitor glucose fluctuation. We induced type 1 diabetes model (T1D) for ten Sprague-Dawley rats using streptozotocin and used five Otsuka Long-Evans Tokushima Fatty rats as obese type 2 diabetes model (OT2D) and 10 Goto-Kakizaki rats as nonobese type 2 diabetes model (NOT2D). We performed the stress loading test in both the normal and diabetic states and compared patterns of glucose fluctuation among the three models. We classified the pattern of glucose fluctuation into A, B, and C types according to speed of change in glucose level. Results: Increase in glucose, total amount of hyperglycemic exposure, time of stress-induced hyperglycemia, and speed of glucose increase were significantly increased in all models compared to the normal state. While the early increase in glucose after exposure to stress was higher in T1D and NOT2D, it was slower in OT2D. The rate of speed of the decrease in glucose level was highest in NOT2D and lowest in OT2D. Conclusion: The diabetic state was more vulnerable to stress compared to the normal state in all models, and the pattern of glucose fluctuation differed among the three types of diabetes. The study provides basic evidence for stress-induced hyperglycemia patterns and characteristics used for the management of diabetes patients.

Lost in Translation? Measuring Diabetic Neuropathy in Humans and Animals

진흥용,문성수,Nigel A. Calcutt 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.1

The worldwide diabetes epidemic is estimated to currently afflict almost 500 million persons. Long-term diabetes damages multiple organ systems with the blood vessels, eyes, kidneys and nervous systems being particularly vulnerable. These complications of diabetes reduce lifespan, impede quality of life and impose a huge social and economic burden on both the individual and society. Peripheral neuropathy is a debilitating complication that will impact over half of all persons with diabetes. There is no treatment for diabetic neuropathy and a disturbingly long history of therapeutic approaches showing promise in preclinical studies but failing to translate to the clinic. These failures have prompted re-examination of both the animal models and clinical trial design. This review focuses on the functional and structural parameters used as indices of peripheral neuropathy in preclinical and clinical studies and the extent to which they share a common pathogenesis and presentation. Nerve conduction studies in large myelinated fibers have long been the mainstay of preclinical efficacy screening programs and clinical trials, supplemented by quantitative sensory tests. However, a more refined approach is emerging that incorporates measures of small fiber density in the skin and cornea alongside these traditional assays at both preclinical and clinical phases.

Effect of Rutin on Diabetic Auditory Neuropathy in an Experimental Rat Model

Aida Doostkam,Hossein Mirkhani,Kamyar Iravani,Saied Karbalay-Doust,Kazem Zarei 대한이비인후과학회 2021 Clinical and Experimental Otorhinolaryngology Vol.14 No.3

Objectives. Diabetic auditory neuropathy is a common complication of diabetes mellitus that has a major impact on patients’ quality of life. In this study, we assessed the efficacy of rutin in treating diabetic auditory neuropathy in an experimental rat model. Methods. Forty Sprague-Dawley rats were randomly assigned to the following groups: group 1, control; group 2, diabetic rats; and groups 3–5, rats treated with rutin (at doses of 50, 100, and 150 mg/kg, respectively). We used auditory brain stem response, stereology of the spiral ganglion, and measurements of superoxide dismutase (SOD) and malondialdehyde (MDA) to evaluate the effects of treatment. Results. Significant improvements in auditory neuropathy were observed in the rutin-treated groups in comparison with the diabetic group (P<0.05). Auditory threshold, wave latency, wave morphology, the volume and number of neurons in the spiral ganglion, and SOD and MDA activity showed improvements following treatment. Conclusion. Rutin shows promise as a treatment modality for diabetic auditory neuropathy, but more trials are warranted for its clinical application.

Experimental animal models for diabetes and its related complications—a review

Chidhambara Priya Dharshini Kottaisamy,Divya S. Raj,V. Prasanth Kumar,Umamaheswari Sankaran 한국실험동물학회 2021 Laboratory Animal Research Vol.37 No.3

Diabetes mellitus, a very common and multifaceted metabolic disorder is considered as one of the fastest growing public health problems in the world. It is characterized by hyperglycemia, a condition with high glucose level in the blood plasma resulting from defects in insulin secretion or its action and in some cases both the impairment in secretion and also action of insulin coexist. Historically, animal models have played a critical role in exploring and describing malady pathophysiology and recognizable proof of targets and surveying new remedial specialists and in vivo medicines. In the present study, we reviewed the experimental models employed for diabetes and for its related complications. This paper reviews briefly the broad chemical induction of alloxan and streptozotocin and its mechanisms associated with type 1 and type 2 diabetes. Also we highlighted the different models in other species and other animals.

당뇨모델 조직내 미토콘드리아 DNA 복제수 감소

김영미,송지현,임선희,한복기,이홍규 국립보건연구원 1998 국립보건원보 Vol.35 No.-

Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions

Md Jakir Hossain,Michael D. Kendig,Meg E. Letton,Margaret J. Morris,Ria Arnold 대한당뇨병학회 2022 Diabetes and Metabolism Journal Vol.46 No.2

Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development.

당뇨병-고지혈증 모델동물의 개발

오승현,노경진,박인선,민본홍,두호경,안세영,김용석,성제경 한국환경독성학회 2004 환경독성보건학회지 Vol.19 No.3

Diabetic complication is one of major risk factors leading to vascular disease Such as atherosclerosis stroke, coronary heart disease and etc Several factors affecting the acceleration of diabetic vascular complication have been known such as hypertension hyperlipidemia, immune complex and genetic factors To screen and develop new therapeutics agents for diabetic vascular complication, it is strongly needed to develop animal models for diabetic complications However in rodents models, diabetic complications is not well developed Furthermore to asses￠ the possibility of new therapeutics for diabetic vascular complications, diabetic animal models which have the risk factors of diabetic complications is needed We aim to develop and establish an diabetic animal model which have diabetic complications with hyperlipidemia which is one of risk factors for diabetic complications We induced insulin-dependent diabetes by intra venous injection of streptozotocin (35 mg/kg/day) in RICO rats which is a spontaneous animal model for hyperlipidemia Our models (STZ RICO) showed hyperglycemia, persistent high level of plasma cholesterol and triglyceridemia with severe diabetic renal changes until 28 weeks after induction of diabetes STZ-RICO rats could be used for the evaluations of newly developed diabetic drugs.

Application of Animal Models in Diabetic Cardiomyopathy

이왕수,김재택 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.2

Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.

Therapy of Diabetes Mellitus Using Experimental Animal Models

Min, T.S.,Park, Soo Hyun Asian Australasian Association of Animal Productio 2010 Animal Bioscience Vol.23 No.5

Diabetes mellitus is a worldwide epidemic with high mortality. As concern over this disease rises, the number and value of research grants awarded by the National Research Foundation of Korea (NRF) have increased. Diabetes mellitus is classified into two groups. Type 1 diabetes requires insulin treatment, whereas type 2 diabetes, which is characterized by insulin resistance, can be treated using a variety of therapeutic approaches. Hyperglycemia is thought to be a primary factor in the onset of diabetes, although hyperlipidemia also plays a role. The major organs active in the regulation of blood glucose are the pancreas, liver, skeletal muscle, adipose tissue, intestine, and kidney. Diabetic complications are generally classified as macrovascular (e.g., stroke and heart disease) or microvascular (i.e., diabetic neuropathy, nephropathy, and retinopathy). Several animal models of diabetes have been used to develop oral therapeutic agents, including sulfonylureas, biguanides, thiazolidinediones, acarbose, and miglitol, for both type 1 and type 2 diseases. This review provides an overview of diabetes mellitus, describes oral therapeutic agents for diabetes and their targets, and discusses new developments in diabetic drug research.