Acute And Chronic Animal Models For The Evaluation Of Anti-diabetic Agents
Acute and chronic animal models for the evaluation of anti-diabetic agents Kumar et al; licensee BioMed Central Ltd.2012 Diabetes mellitus is a potentially morbid condition with high prevalence worldwide thus being a major medical concern. Experimental induction of diabetes mellitus in animal models is essential for the advancement of our knowledge and understanding of the various aspects of its pathogenesis and ultimately finding new therapies and cure. Experimental diabetes mellitus is generally induced in laboratory animals by several methods that include: chemical, surgical and genetic (immunological) manipulations. Most of the experiments in diabetes are carried out in rodents, although some studies are still performed in larger animals. The present review highlights the various methods of inducing diabetes in experimental animals in order to test the newer drugs for their anti-diabetic potential. Streptozotocinalloxandiabetic ratsanimal modelsdiabetes WHO reports Diabetes mellitus as one of the most common public health problems which will affect a total population of 220 million worldwide in the year 2020 [ 1 , 2 ]. The increasing prevalence of diabetes mellitus worldwide is a major societal issue because diabetes is a complex and multifactorial origin disease. The prevalence of diabetes is rising all over the world due to population growth, aging, urbanization and an increase of obesity and physical inactivity. Unlike in the West, where older persons are most affected, diabetes in Asian countries is disproportionately high in young to middle-aged adults. This could have long-lasting adverse effects on a nation's health and economy, especially for developing countries. The International Diabetes Federation (IDF) estimates the total number of people in India with Continue reading >>
Experimental Diabetes Mellitus In Different Animal Models
Experimental Diabetes Mellitus in Different Animal Models Amin Al-awar ,1 Krisztina Kupai ,1,* Mdea Veszelka ,1 Gerg Szcs ,1 Zouhair Attieh ,2 Zsolt Murlasits ,3 Szilvia Trk ,1 Anik Psa ,1 and Csaba Varga 1 1Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep Fasor 52, 6726 Szeged, Hungary 1Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep Fasor 52, 6726 Szeged, Hungary 1Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep Fasor 52, 6726 Szeged, Hungary 1Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep Fasor 52, 6726 Szeged, Hungary 2Department of Laboratory Science and Technology, Faculty of Health Sciences, American University of Science and Technology, Alfred Naccache Avenue, Beirut 1100, Lebanon 1Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep Fasor 52, 6726 Szeged, Hungary 1Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep Fasor 52, 6726 Szeged, Hungary 1Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep Fasor 52, 6726 Szeged, Hungary 1Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep Fasor 52, 6726 Szeged, Hungary 2Department of Laboratory Science and Technology, Faculty of Health Sciences, American University of Science and Technology, Alfred Naccache Avenue, Beirut 1100, Lebanon 3Sport Science Program, Qatar University, Doha, Qatar Received 2016 Continue reading >>
Novel Insights Into The Animal Models Of Diabetes Mellitus
Novel Insights into the Animal models of Diabetes Mellitus Animal models of disease have historically played a crucial role in the investigation and explanation of disease pathophysiology and identification of drug targets. Moreover, animal models also played important role in the assessment of new drugs in vivo. Diabetes mellitus is a group of metabolic ailments, which is characterized by high blood sugar levels for a longer period. To avoid complications of disease and related economic losses and untoward concerns, prevention and early therapy are therefore necessary. Because of the inadequate usefulness of the current therapies, new therapeutic agents are required to be developed. This paper briefly reviews the animal models of type 1 and type 2 diabetes mellitus, which include natural model of diabetes, models of diabetes induced by chemicals, genetic models of diabetes, physiological model, non-obese model, surgery induced model of diabetes mellitus. Our study found that animal models played an important role in the investigation of the pathophysiology of diabetes mellitus. Also, they helped in the understanding of drug targets and testing new drugs for the mentioned disease. Additionally, a number of animal models for type 2 diabetes mellitus have been developed which also has obesity. This reflects the linkage between obesity and diabetes, a condition similar to that of the human type i.e. connection between obesity and diabetes mellitus. These animal models have abnormality in one or more genes that are connected to obesity and insulin resistance, which leads to the development of hyperglycemia [11]. There are a number of factors that affect pathogenesis of diabetes mellitus and its complications; they include obesity, insulin resistance, hyperglycemia, hyperli Continue reading >>
Diabetic Animal Models | Diabetic Neuropathology & Nephropathy | Taconic Biosciences | Taconic Biosciences
A suitable model for the study of diabetic neuropathology and nephropathy Also used in the study of the pathogenesis and prevention of Type II Non-Insulin Dependent Diabetes Mellitus (NIDDM) Experiences a hyperinsulinemic phase (Phase 1) followed by a hypoinsulinemic phase (Phase 2) at 2-3 months of age Genotype shown in the table above refers to the Lepr gene Due to possible crossover of the misty (m) and Leprdb genes, a low percentage of DB-M could be heterozygous for the misty (m) gene Only homozygotes (black) are diabetic and obese, heterozygotes (black) and wild types (misty) are non-diabetic and lean *Pricing is for ungenotyped lean or obese animals. Customers wanting genotyped animals must allow for an extra 2 week leadtime. The Diabetic Spontaneous mutant model was developed by Hummel et al in 1959 by discovering a Lepr db mutation on a C57BLKS background. M&B A/S (now Taconic Europe) received stock from CERJ France in 1991. The mice were derived by embryo transfer in 2005 at Taconic US and are maintained by incrossing brother x sister mice. Strain Profile: Akp1a, Akp2a, Anpepa, Car2a, Es1a, Es2b, Es3a, Es5b, Es9a, G6pd1a, Gpi1b, Got2b, Hbbs, Idh1b, Ldr1a, Ldr2a, Mod1b, Mup1b, Pep3b, Pgm1a, Trfb Diabetic Spontaneous Mutant Mouse Phenotypic Characteristics Phenotype: Phenotypically, the diabetic mouse (C57BLKS db/db) is identical with the obese mouse (C57BL/6J ob/ob), however the syndrome in C57BLKS db/db is far more severe than in the C57BL/6J ob/ob mouse. The clinical picture is dependent on the background strain in which the gene is expressed. If the ob gene is transferred to C57BLKS, Ks ob/ob this strain will develop a more severe form of diabetes than that observed in the C57BL/6J strain, indicating that these two strains differ in their capacity to adapt t Continue reading >>
Mouse Models Of Diabetes, Obesity And Related Kidney Disease
Mouse Models of Diabetes, Obesity and Related Kidney Disease Affiliations Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia, Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, St Leonards, NSW 2065, Australia Affiliation School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, Australia Affiliation Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia Affiliation Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, St Leonards, NSW 2065, Australia Affiliation Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia Affiliation Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia Affiliation Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia Affiliation Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia Continue reading >>
In Vivo Diabetes Studies - Animal Models Of Diabetes - Crownbio
Most Translational Platforms for Diabetes Research CrownBio has developed unique rodent and non-human primate (NHP) based translational platforms that replicate the human pre-diabetic state, diabetes progression, and development of diabetic complications, and help support transition of new anti-diabetic agents from lead compounds into the clinic. Most translational rodent and NHP models of diabetes Replicate all stages of disease progression and associated complications Supported by a comprehensive platform of analytical services Useful for modeling various stages of diabetes and for testing therapeutic interventions at different disease stages Evaluate Efficacy of Anti-Diabetes Drugs in Rodent and NHP Platforms Diabetes is a group of metabolic diseases quantified by increased blood sugar levels for a prolonged period of time. The most common form of diabetes is Type 2, a chronic progressive disease, characterized by hyperglycemia due to insufficient insulin production and/or cellular insulin resistance. Type 2 diabetes is largely the result of excess body weight, unhealthy diet, inactivity, and aging; therefore, as worldwide obesity levels increase and lifestyles become more sedentary, Type 2 diabetes rates have reached epidemic proportions. A key challenge in diabetes research and drug development is that most animal models do not completely mimic the complex states of disease progression and associated complications, thereby limiting their translatability. CrownBios unique rodent and NHP platforms enable predicting human response to drug candidates in anti-diabetes programs. Combined with our CVMD services, we enable clients to test which candidate has the highest chance of success in the clinic and inform strategic go/no-go decisions. Rodent models of diabetes incl Continue reading >>
Animal Models Of Obesity And Diabetes Mellitus
Animal models of obesity and diabetes mellitus Nature Reviews Endocrinology volume 14, pages 140162 (2018) | Download Citation More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions. In this Review, we consolidate the key information on the currently available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models. Development of safe and potent therapeutics is required to combat the obesity and diabetes mellitus pandemic Animal models remain indispensable for discovering, validating and optimizing novel therapeutics for their safe use in humans To improve the transition from bench to bedside, researchers must select the appropriate models, beware a myriad of confounding factors and draw appropriate conclusions Experimental procedures and conditions should be accurately detailed to improve the reproducibility and translation of findings in preclinical animal models Different animal models, ranging from non-mammalian models to non-human primates, each have distinct advantages and limitations Continue reading >>
Visualization Of Methylglyoxal In Living Cells And Diabetic Mice Model With A 1,8-naphthalimide-based Two-photon Fluorescent Probe
Visualization of methylglyoxal in living cells and diabetic mice model with a 1,8-naphthalimide-based two-photon fluorescent probe a State Key Laboratory of Fine Chemicals, Dalian University of Technology, No. 2 Linggong Road, Dalian 116024, P. R. China Methylglyoxal (MGO), a dicarbonyl metabolite, is the most studied precursor of advanced glycation end-products (AGEs) and its elevated levels have also been associated with various pathologies. Hence, the development of effective methods for monitoring MGO in live cells and in vivo is of great importance for ascertaining the onset and progress of related diseases. Herein, we designed and synthesized an endoplasmic reticulum-targeting two-photon fluorescent probe called NI-OPD for the detection of MGO with high selectivity, sensitivity, and hypotoxicity. The probe was successfully applied for monitoring MGO in living cells and a diabetic mice model. The two-photon fluorescence images confirmed that the endogenous MGO in the liver and kidney tissues of diabetic mice is higher than that of normal mice. Furthermore, it revealed that after treatment with metformin, a widely used hypoglycemia drug, the diabetic mice showed a decreased concentration of MGO in liver and kidney tissues. Thus, NI-OPD may serve as a useful tool for the detection of MGO and for studying the relationships between MGO and pathological and biological processes in biosystems. The article was received on 12 Jun 2018, accepted on 13 Jul 2018and first published on 16 Jul 2018 Visualization of methylglyoxal in living cells and diabetic mice model with a 1,8-naphthalimide-based two-photon fluorescent probe M. Yang, J. Fan, J. Zhang, J. Du and X. Peng, Chem. Sci., 2018,9, 6758 This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Un Continue reading >>
The Use Of Animal Models In Diabetes Research
The use of animal models in diabetes research Diabetes Research Group, King's College London, London, UK Aileen King, Diabetes Research Group, Guy's Campus, King's College London, London SE1 1UL, UK. E-mail: [email protected] Received 2011 Aug 19; Revised 2012 Feb 10; Accepted 2012 Feb 13. Copyright 2012 The Author. British Journal of Pharmacology 2012 The British Pharmacological Society This article has been cited by other articles in PMC. Diabetes is a disease characterized by a relative or absolute lack of insulin, leading to hyperglycaemia. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is due to an autoimmune destruction of the insulin-producing pancreatic beta cells, and type 2 diabetes is caused by insulin resistance coupled by a failure of the beta cell to compensate. Animal models for type 1 diabetes range from animals with spontaneously developing autoimmune diabetes to chemical ablation of the pancreatic beta cells. Type 2 diabetes is modelled in both obese and non-obese animal models with varying degrees of insulin resistance and beta cell failure. This review outlines some of the models currently used in diabetes research. In addition, the use of transgenic and knock-out mouse models is discussed. Ideally, more than one animal model should be used to represent the diversity seen in human diabetic patients. This paper is the latest in a series of publications on the use of animal models in pharmacology research. Readers might be interested in the previous papers. Robinson V (2009). Less is more: reducing the reliance on animal models for nausea and vomiting research. Holmes AM, Rudd JA, Tattersall FD, Aziz Q, Andrews PLR (2009). Opportunities for the replacement of animals in the study of nausea and vomiting. Continue reading >>
Animal Models Of Diabetic Retinopathy: Summary And Comparison
Animal Models of Diabetic Retinopathy: Summary and Comparison 1Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 2Research Center of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Received 10 January 2013; Revised 2 September 2013; Accepted 2 September 2013 Copyright 2013 Angela Ka Wai Lai and Amy C. Y. Lo. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Diabetic retinopathy (DR) is a microvascular complication associated with chronic exposure to hyperglycemia and is a major cause of blindness worldwide. Although clinical assessment and retinal autopsy of diabetic patients provide information on the features and progression of DR, its underlying pathophysiological mechanism cannot be deduced. In order to have a better understanding of the development of DR at the molecular and cellular levels, a variety of animal models have been developed. They include pharmacological induction of hyperglycemia and spontaneous diabetic rodents as well as models of angiogenesis without diabetes (to compensate for the absence of proliferative DR symptoms). In this review, we summarize the existing protocols to induce diabetes using STZ. We also describe and compare the pathological presentations, in both morphological and functional aspects, of the currently available DR animal models. The advantages and disadvantages of using different animals, ranging from zebrafish, rodents to other higher-order mammals, are also discussed. Until now, there is no single model that displays all the clinical features of DR Continue reading >>
Animal Models Of Diabetes Mellitus.
Department of Medicine, University of Wales College of Medicine, Cardiff, UK. Animal models have been used extensively in diabetes research. Early studies used pancreatectomised dogs to confirm the central role of the pancreas in glucose homeostasis, culminating in the discovery and purification of insulin. Today, animal experimentation is contentious and subject to legal and ethical restrictions that vary throughout the world. Most experiments are carried out on rodents, although some studies are still performed on larger animals. Several toxins, including streptozotocin and alloxan, induce hyperglycaemia in rats and mice. Selective inbreeding has produced several strains of animal that are considered reasonable models of Type 1 diabetes, Type 2 diabetes and related phenotypes such as obesity and insulin resistance. Apart from their use in studying the pathogenesis of the disease and its complications, all new treatments for diabetes, including islet cell transplantation and preventative strategies, are initially investigated in animals. In recent years, molecular biological techniques have produced a large number of new animal models for the study of diabetes, including knock-in, generalized knock-out and tissue-specific knockout mice. Continue reading >>
Choosing Among Type Ii Diabetes Mouse Models
JAX has been distributing mouse models for type II diabetes (Non-insulin Dependent Diabetes; NIDD; T2D) since the 1960s, and today there are several models to choose from. Unfortunately, no single diabetic mouse model recapitulates all of the features or complications of human diabetes. How, then, do you choose which model (or models) to use in your research? Indeed, one of the most common diabetes-related questions we receive in Technical Information is “Which diabetes model is ‘The Best’?” Below is a broad overview of diabetes models that are available from JAX and some considerations to help you to make your decision. Diabetes Phase I, II or III? First some orientation: Diabetes in humans typically develops through a progressive series of increasingly severe stages (or phases): • Pre-diabetes: Characterized by impaired glucose tolerance – difficulty clearing glucose following a meal – postprandial hyperglycemia, and (or) decreased sensitivity to insulin. • Phase I: Postprandial as well as basal hyperglycemia; insulin-producing beta cells in the pancreas are increasingly dysfunctional. • Phase II: Fasting hyperglycemia and significant beta cell atrophy. • Phase III (end stage): Beta cells can no longer release insulin; insulin replacement therapy is required. Choosing an appropriate diabetes model depends on the severity of diabetes you wish to study. As in humans, mouse models of T2D are obese, but vary in severity – some models are morbidly obese, whereas others manifest more moderate obesity. Diet-induced Obesity (DIO) Mice: Modeling Pre-Diabetes Obesity is one of the greatest risk factors linked to diabetes in humans, and similar to humans, some mouse strains become obese when fed high-fat or so-called “Western” diets. Among mouse strains Continue reading >>
The Use Of Animal Models In The Study Of Diabetes Mellitus
Abstract Animal models have enormously contributed to the study of diabetes mellitus, a metabolic disease with abnormal glucose homeostasis, due to some defect in the secretion or the action of insulin. They give researchers the opportunity to control in vivo the genetic and environmental factors that may influence the development of the disease and establishment of its complications, and thus gain new information about its handling and treatment in humans. Most experiments are carried out on rodents, even though other species with human-like biological characteristics are also used. Animal models develop diabetes either spontaneously or by using chemical, surgical, genetic or other techniques, and depict many clinical features or related phenotypes of the disease. In this review, an overview of the most commonly used animal models of diabetes are provided, highlighting the advantages and limitations of each model, and discussing their usefulness and contribution in the field of diabetes research. Type I Diabetes (T1DM) Models T1DM, a multifactorial autoimmune disease involving genetic and environmental factors, is hallmarked by T-cell and macrophages-mediated destruction of pancreatic β-cells, resulting in irreversible insulin deficiency. Diabetic ketoacidosis, a T1DM immediate consequence, can be fatal without treatment, while the long-term vascular T1DM complications affecting several organs and tissues can significantly affect life expectancy. There is no doubt that T1DM susceptibility is MHC-dependent and MHC genes account for approximately 50% of the total contribution to the disease. However, although to date studies corroborate that both HLA-DR and HLA-DQ genes are important in determining disease risk, the effects of individual alleles may be modified by the h Continue reading >>
Spontaneous Type 2 Diabetic Rodent Models
Spontaneous Type 2 Diabetic Rodent Models Department of Nephrology, Second Hospital of Jilin University, Changchun 130041, China Received 22 November 2012; Revised 8 January 2013; Accepted 22 January 2013 Copyright 2013 Yang-wei Wang et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Diabetes mellitus, especially type 2 diabetes (T2DM), is one of the most common chronic diseases and continues to increase in numbers with large proportion of health care budget being used. Many animal models have been established in order to investigate the mechanisms and pathophysiologic progress of T2DM and find effective treatments for its complications. On the basis of their strains, features, advantages, and disadvantages, various types of animal models of T2DM can be divided into spontaneously diabetic models, artificially induced diabetic models, and transgenic/knockout diabetic models. Among these models, the spontaneous rodent models are used more frequently because many of them can closely describe the characteristic features of T2DM, especially obesity and insulin resistance. In this paper, we aim to investigate the current available spontaneous rodent models for T2DM with regard to their characteristic features, advantages, and disadvantages, and especially to describe appropriate selection and usefulness of different spontaneous rodent models in testing of various new antidiabetic drugs for the treatment of type 2 diabetes. In nearly all countries of the world, diabetes mellitus is one of the most common chronic diseases and continues to increase in numbers and significance, because of the reduced physical Continue reading >>
Diabetes: Models, Signals, And Control
Abstract: The control of diabetes is an interdisciplinary endeavor, which includes a significant biomedical engineering component, with traditions of success beginning in the early 1960s. It began with modeling of the insulin-glucose system, and progressed to large-scale in silico experiments, and automated closed-loop control (artificial pancreas). Here, we follow these engineering efforts through the last, almost 50 years. We begin with the now classic minimal modeling approach and discuss a number of subsequent models, which have recently resulted in the first in silico simulation model accepted as substitute to animal trials in the quest for optimal diabetes control. We then review metabolic monitoring, with a particular emphasis on the new continuous glucose sensors, on the analyses of their time-series signals, and on the opportunities that they present for automation of diabetes control. Finally, we review control strategies that have been successfully employed in vivo or in silico, presenting a promise for the development of a future artificial pancreas and, in particular, discuss a modular architecture for building closed-loop control systems, including insulin delivery and patient safety supervision layers. We conclude with a brief discussion of the unique interactions between human physiology, behavioral events, engineering modeling and control relevant to diabetes. Continue reading >>
