Other Models of Type I Diabetes
John H. McNeill in Experimental Models of Diabetes, 2018
In this chapter the chemical and surgical induction of Type I diabetes models other than streptozotocin (STZ) diabetes will be discussed along with some comparisons to the more commonly used STZ diabetic model. The mechanism by which alloxan induces diabetes is considered, followed by a discussion of the nature of the diabetic state in rabbits where alloxan is widely used to study the long-term complications of diabetes. Alloxan is used to induce diabetes in numerous species, and the advantages and disadvantages as compared with STZ are discussed. Pancreatectomy is also used in a wide variety of species. This model is favoured in studies of pancreas and islet cell transplantation. Some of its advantages compared with chemical induction of diabetes are discussed. Dexamethasone can be used to induce models of both insulin-dependent and noninsulin-dependent diabetes. When investigators have wanted a model in which the mechanism of induction of diabetes includes, at least partly, the immune response that occurs in IDDM in humans, STZ combined with complete Freund’s adjuvant has been used. The models discussed in this chapter are used to a lesser extent than STZ diabetes but are still very important.
Research Models of Diabetes Mellitus
Grant N. Pierce, Robert E. Beamish, Naranjan S. Dhalla in Heart Dysfunction in Diabetes, 2019
The capacity of alloxan and streptozotocin to induce diabetes was discovered by accident. Dunn et al.51 were the first to report the diabetogenic action of alloxan. Working in Glasgow in 1943, these researchers were attempting to elucidate the mechanisms responsible for kidney dysfunction. A model of renal failure was needed and they were studying agents which, upon injection, may cause such a lesion. Since it was known at the time that uric acid elicited toxic effects on the kidney, they were investigating the effects of uric acid and some related derivatives on renal integrity. Injection of the uric acid derivative, alloxan, into rabbits did produce lesions in the kidney. However, many animals died soon after treatment from causes which were obviously distinct from the renal complications. Further investigation51 revealed a derangement in plasma glucose homeostasis and necrotic damage to the pancreatic β cells. Homologues and compounds related to alloxan are also capable of causing diabetes. These include N-methyl propylalloxan, ethyl propylalloxan, alloxantin, dimethylalloxantin, diethylalloxantin, dialuric acids, and methyldialuric acids.52 The identification of alloxan as a diabetogenic agent was of obvious importance for the study of the cause of diabetes mellitus.
Medicinal Plants Research
Vikas Kumar, Addepalli Veeranjaneyulu in Herbs for Diabetes and Neurological Disease Management, 2018
The study of diabetes in humans has drawbacks by genetic heterogeneity, a wide variety of lifestyles, relative inaccessibility to tissues and organs and, of course, ethical considerations. Using AM can solve some of these problems, but obviously extrapolating results from animals to humans carry some risk. AM are an excellent tool or study of clinical and pathological aspects of IDDM development and progress. Experimental induction of DM in AM is essential for the advancement of our knowledge and understanding of the various aspects of its pathogenesis and it has the great advantage to eliminate factors such as ethnicity, economic and geographic variables, drug interactions, diet, gender, and age differences that significantly limit clinical trial. Indeed, appropriate AM have provided important information on genetic and environmental risks of diabetes, and helped to dissect molecular mechanisms underlying the development, progression, and therapeutic control of this disease.116 The decision about the experimental AM to be used for a particular experiment is often multifactorial. Ideally, experiments should be carried out in several different models, considering that none of them completely reflects the complexity of human DM. Then AM for evaluation of herbal medicines most commonly used are described and their advantages and disadvantages are discussed, as a result. The most commonly used and affordable AM produced for study of IDDM are: (1) chemically induced via streptozotocin (STZ), alloxan,117 ferric nitrilotriacetate,118 and dithizone;119 (2) spontaneous autoimmune; (3) genetically induced insulin-dependent; (4) non-rodent; and (5) virally induced. The chemically induced IDDM model, which cause distraction of the β-cells and rapid hyperglycemia, motor incoordination, nerve degeneration, demylination, and loss of epidermal nerve fiber, can lead to the multiple organs toxicity (especially kidneys),120 and change isozymes.121 Induction of experimental diabetes in the rat using STZ is very convenient and simple to use122,123 and STZ injection leads to the degeneration of the Langerhans islets beta cells.124,125 Alloxan, a well- known diabetogenic agent is widely used to induce type 2 diabetes in animals.126 The drug and its reduction product dialuric acid establish a redox cycle with the formation of superoxide radicals. These radicals undergo dismutation to hydrogen peroxide. Thereafter, highly reactive hydroxyl radicals are formed by fenton reaction. The action of ROS with a simultaneous massive increase in cytosolic calcium concentration causes rapid destruction of b cells.120 The dose of these agents required for inducing diabetes depends on the animal species, route of administration and nutritional status127 is a naturally occurring, broad spectrum antibiotic and cytotoxic chemical that is particularly toxic to the pancreatic, insulin producing beta cells in mammals.120,128–130
Leaf extract of Morinda lucida improves pancreatic beta-cell function in alloxan-induced diabetic rats
Published in Egyptian Journal of Basic and Applied Sciences, 2019
Adam Olaitan Abdulkareem, Adedoyin Igunnu, Adeola Adefoluke Ala, Lawrence Aderemi Olatunji
This study investigated the effect of aqueous leaf extract of M. lucida on pancreatic beta-cell function and dyslipidemia in type 1 diabetic rats, using alloxan induction. Alloxan is a cytotoxic diabetogenic compound, widely used in experimental diabetes research [32]. It stimulates insulin-dependent diabetes (T1D) by inducing selective necrosis of the beta-cells of pancreatic islets, thus, destroying β-cells and reducing their function [33,34]. Our results showed that M. lucida aqeous leaf extract lowered alloxan-induced hyperglycemia at low dose (120 mg/kg), which compared favorably with glibenclamide. The main etiology of T1D is destruction of pancreatic β-cells [35]. In this study, treatment of diabetic rats with the extract improved pancreatic β-cell function and thus, insulin production, better than the standard drug (glibenclamide) used. This may imply that, the leaf extract of M. lucida induced regeneration of pancreatic β-cell, and hence, enhanced its function. Our observation agrees with an earlier study, which reported that leaf extracts of M. lucida ameliorated alloxan-induced pancreatic damage [36].
Early ultra- and microstructural alterations in rat pancreas in alloxan-induced diabetes mellitus
Published in Ultrastructural Pathology, 2020
A. A. Titova, M. O. Mavlikeev, M. S. Kaligin, D.M. Suleymanova, I. A. Chekmaryeva, A.P. Kiyasov, R. V. Deev
Alloxan-induced diabetes is one of the most commonly used and easily reproducible models of diabetes mellitus (DM).1 Alloxan is a pyrimidine derivative being an unstable hydrophilic compound similar to glucose in structure.2 GLUT-2, a glucose transporter via the plasmatic membrane recognizes alloxan as a glucose analogue and transports its molecule into the cytosol of β-cells of the Langerhans islets (LIs).3 Alloxan is involved in the formation of dialuric acid in the presence of intracellular thiols.4 Dialuric acid autooxidation leads to releasing superoxide radicals, hydrogen peroxide, and as a result of a final reaction catalyzed by ferrous ions, – highly reactive hydroxyl radicals.5 In addition, alloxan causes increased intracellular concentrations of calcium ions,6 inhibits a glucose sensor glucokinase that in combination with free radical generation leads to β-cell injury and death, hypoinsulinemia and hyperglycemia.7
The action of low doses of persistent organic pollutants (POPs) on mitochondrial function in zebrafish eyes and comparison with hyperglycemia to identify a link between POPs and diabetes
Published in Toxicology Mechanisms and Methods, 2020
Eun Ko, Dayoung Kim, Kitae Kim, Moonsung Choi, Sooim Shin
Zebrafish (Danio rerio) has been recently used as a vertebrate model in studies of toxicology and metabolic diseases (Hill et al. 2005; Seth et al. 2013). The experimental advantages of zebrafish include their rapid ontogeny and ease of genetic and protein manipulations designed to clarify physiological and pathological conditions (Asaoka et al. 2014; Stewart et al. 2014). Hyperglycemia associated with T2D can be induced in zebrafish using streptozotocin, alloxan, or high-fat diets (Zimmet et al. 2004; King 2012; Skovso 2014). Streptozotocin and alloxan are the most predictable means of inducing a diabetic condition. However, they have side effects on biological systems due to their toxicity (Szkudelski 2001). High-fat diet-induced obesity in zebrafish also produces hyperglycemia and hypertriglyceridemia, but the process takes at least 8 weeks (Gleeson et al. 2007; Oka et al. 2010).