scholarly journals DIFFERENT EXPERIMENTAL MODELS USED TO INDUCE DIABETES MELLITUS IN RODENTS: A REVIEW

2019 ◽  
pp. 60-62
Author(s):  
RESHMI CHAKRABORTY ◽  
ABDUL BAQUEE AHMED ◽  
DIPANKAR SAHA
Keyword(s):  
Progressive Increase ◽  
Experimental Models ◽  
Abdominal Circumference ◽  
Cytotoxic Action ◽  
Β Cells ◽  
Diabetes In Animals ◽  
Autoimmune Destruction ◽  
Experimental Rat Model ◽  
Impaired Insulin Action ◽  
Abdominal Fat Deposition

Diabetes is a metabolic disease characterized by the presence of hyperglycemia resulting from either defects in insulin secretion or action or both. Various processes are involved in the development of diabetes. These range from autoimmune destruction of the insulin-producing cells, β-cells of the pancreas, a dysfunction of the pancreatic β-cell, and impaired insulin action through insulin resistance. Experimental diabetes in animals are widely induced by administration of alloxan and streptozotocin at a proper dose. The mechanism of their action in pancreatic β-cells has been extensively investigated. Reactive oxygen species are responsible for the cytotoxic action of both these diabetogenic agents. However, the source of their generation is different in the case of alloxan (ALX) and streptozotocin (STZ). In one of the study, it is also showed that the administration of a high-fat diet (HFD) to rats for 16 w showed a progressive increase in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia and hyperinsulinemia. Administration of alloxan or streptozotocin in addition with HFD is also able to induce diabetes in an experimental rat model.

scholarly journals Increased Incidence of Type 1 Diabetes during the COVID-19 Pandemic in Romanian Children

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 973
Author(s):  
Adrian Vlad ◽  
Viorel Serban ◽  
Romulus Timar ◽  
Alexandra Sima ◽  
Veronica Botea ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Background Information ◽  
First Year ◽  
Age Group ◽  
Newly Diagnosed ◽  
Β Cells ◽  
Specific Antibodies ◽  
Autoimmune Destruction ◽  
Geographical Regions

Background and Objective: It is known that several viruses are involved in the pathogenesis of type 1 diabetes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new worldwide spread virus that may act as a trigger for the autoimmune destruction of the β-cells, as well, and thus lead to an increase in the incidence of type 1 diabetes. Material and Methods: The Romanian National Organization for the Protection of Children and Adolescents with Diabetes (ONROCAD) has collected information regarding new cases of type 1 diabetes in children aged 0 to 14 years from all over the country since 1996 and has computed the incidence of type 1 diabetes in this age group. Results: We observed a marked increase in the incidence of type 1 diabetes in the first year of the COVID-19 pandemic, with 16.9%, from 11.4/100,000 in 2019 to 13.3/100,000 in 2020, much higher compared to previous years (mean yearly increase was 5.1% in the period 1996–2015 and 0.8% in the interval 2015–2019). The proportion of newly diagnosed cases was significantly higher in the second half of 2020 compared to the second half of the previous years (57.8 vs. 51%, p < 0.0001). Conclusions: All these aspects suggest the role that SARS-CoV-2 could have in triggering pancreatic autoimmunity. To confirm this, however, collecting information from larger populations from different geographical regions, monitoring the incidence curves over a period of several years, and gathering background information on COVID-19 and/or data on COVID-19 specific antibodies are needed.

scholarly journals Gene Transfection and Expression of Transforming Growth Factor-β1 in Nonobese Diabetic Mouse Islets Protects β-Cells in Syngeneic Islet Grafts from Autoimmune Destruction

2002 ◽  
Vol 11 (6) ◽  
pp. 519-528 ◽  
Author(s):  
Wilma L. Suarez-Pinzon ◽  
Yvonne Marcoux ◽  
Aziz Ghahary ◽  
Alex Rabinovitch
Keyword(s):  
Transforming Growth Factor ◽  
Islet Cells ◽  
Gene Transfection ◽  
Nod Mice ◽  
Nod Mouse ◽  
Β Cells ◽  
Nonobese Diabetic ◽  
Autoimmune Destruction ◽  
Mouse Islets ◽  
Tgf Β1

Nonobese diabetic (NOD) mice develop diabetes and destroy syngeneic islet grafts through an autoimmune response. Because transforming growth factor (TGF)-β1 downregulates immune responses, we tested whether overexpression of TGF-β1 by gene transfection of NOD mouse islets could protect β-cells in islet grafts from autoimmune destruction. NOD mouse islet cells were transfected with an adenoviral DNA expression vector encoding porcine latent TGF-β1 (Ad TGF- β1) or the adenoviral vector alone (control Ad vector). The frequency of total islet cells expressing TGF-1 protein was increased from 12±1% in control Ad vector-transfected cells to 89 ± 4% in Ad TGF-β1-transfected islet cells, and the frequency of β-cells that expressed TGF-β1 was increased from 12 ± 1% to 60 ± 7%. Also, secretion of TGF-β1 was significantly increased in islets that overexpressed TGF-β1. Ad TGF-β1-transfected NOD mouse islets that overexpressed TGF-β1 prevented diabetes recurrence after transplantation into diabetic NOD mice for a median of 22 days compared with only 7 days for control Ad vector-transfected islets (p = 0.001). Immunohistochemical examination of the islet grafts revealed significantly more TGF-β1+ cells and insulin+ cells and significantly fewer CD45+ leukocytes in Ad TGF-β1-transfected islet grafts. Also, islet β-cell apoptosis was significantly decreased whereas apoptosis of graft-infiltrating leukocytes was significantly increased in Ad TGF-β1-transfected islet grafts. These observations demonstrate that overexpression of TGF-β1, by gene transfection of NOD mouse islets, protects islet β-cells from apoptosis and autoimmune destruction and delays diabetes recurrence after islet transplantation.

scholarly journals METABOLIC PHENOTYPING GUIDELINES: Assessing glucose homeostasis in rodent models

2014 ◽  
Vol 222 (3) ◽  
pp. G13-G25 ◽  
Author(s):  
James E Bowe ◽  
Zara J Franklin ◽  
Astrid C Hauge-Evans ◽  
Aileen J King ◽  
Shanta J Persaud ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Β Cells ◽  
Advantages And Disadvantages ◽  
Autoimmune Destruction ◽  
Normal Glucose

The pathophysiology of diabetes as a disease is characterised by an inability to maintain normal glucose homeostasis. In type 1 diabetes, this is due to autoimmune destruction of the pancreatic β-cells and subsequent lack of insulin production, and in type 2 diabetes it is due to a combination of both insulin resistance and an inability of the β-cells to compensate adequately with increased insulin release. Animal models, in particular genetically modified mice, are increasingly being used to elucidate the mechanisms underlying both type 1 and type 2 diabetes, and as such the ability to study glucose homeostasisin vivohas become an essential tool. Several techniques exist for measuring different aspects of glucose tolerance and each of these methods has distinct advantages and disadvantages. Thus the appropriate methodology may vary from study to study depending on the desired end-points, the animal model, and other practical considerations. This review outlines the most commonly used techniques for assessing glucose tolerance in rodents and details the factors that should be taken into account in their use. Representative scenarios illustrating some of the practical considerations of designingin vivoexperiments for the measurement of glucose homeostasis are also discussed.

scholarly journals Beyond Genetic Borders: Sardinian Exposure And Type 1 Diabetes

2018 ◽  
Vol 3 (2) ◽  
Keyword(s):  
Type 1 Diabetes ◽  
Environmental Factors ◽  
Diabetic Patients ◽  
Β Cells ◽  
Autoimmune Destruction ◽  
The People ◽  
Technological Advances ◽  
Chronic Childhood

Type 1 diabetes mellitus (T1D), one of the most chronic childhood disease, results from an autoimmune destruction of pancreatic β cells producing insulin, with insulin deficiency. Recently significant technological advances have been achieved in treatment and quality of life in diabetic patients but the causes are still uncertain, so it is still very difficult to foresee the possible prevention of this disease. The genetic factors alone do not explain the high risk of T1D, sharply increased over the last 40 years in Sardinia, with the second highest risk in the world after Finland, even as many of the people genetically predisposed to T1D do not develop the disease [1]. It is still unknown why some people develop T1D although it is agreed that genetic, non-genetic and probably epigenetic environmental factors all together contribute to the disease. The environmental factors are probably very important for both the development and the increase of T1D. The epigenetic factor possible interrelationships are to be cleared at most.

scholarly journals Reversal of autoimmunity by mixed chimerism enables reactivation of β cells and transdifferentiation of α cells in diabetic NOD mice

2020 ◽  
Vol 117 (49) ◽  
pp. 31219-31230
Author(s):  
Shanshan Tang ◽  
Mingfeng Zhang ◽  
Samuel Zeng ◽  
Yaxun Huang ◽  
Melissa Qin ◽  
...  
Keyword(s):  
Nod Mice ◽  
Lineage Tracing ◽  
Mixed Chimerism ◽  
Cell Regeneration ◽  
Β Cells ◽  
Β Cell ◽  
Nonobese Diabetic ◽  
Autoimmune Destruction ◽  
Epidermal Growth

Type 1 diabetes (T1D) results from the autoimmune destruction of β cells, so cure of firmly established T1D requires both reversal of autoimmunity and restoration of β cells. It is known that β cell regeneration in nonautoimmune diabetic mice can come from differentiation of progenitors and/or transdifferentiation of α cells. However, the source of β cell regeneration in autoimmune nonobese diabetic (NOD) mice remains unclear. Here, we show that, after reversal of autoimmunity by induction of haploidentical mixed chimerism, administration of gastrin plus epidermal growth factor augments β cell regeneration and normalizes blood glucose in the firmly established diabetic NOD mice. Using transgenic NOD mice with inducible lineage-tracing markers for insulin-producing β cells, Sox9+ductal progenitors, Nestin+mesenchymal stem cells, and glucagon-producing α cells, we have found that both reactivation of dysfunctional low-level insulin expression (insulinlo) β cells and neogenesis contribute to the regeneration, with the latter predominantly coming from transdifferentiation of α cells. These results indicate that, after reversal of autoimmunity, reactivation of β cells and transdifferentiation of α cells can provide sufficient new functional β cells to reach euglycemia in firmly established T1D.

scholarly journals Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers

2017 ◽  
Vol 88 (5) ◽  
pp. 307-315 ◽  
Author(s):  
Mireia Fonolleda ◽  
Marta Murillo ◽  
Federico Vázquez ◽  
Joan Bel ◽  
Marta Vives-Pi
Keyword(s):  
Type 1 Diabetes ◽  
Immunological Tolerance ◽  
Exogenous Insulin ◽  
Β Cells ◽  
Clinical Onset ◽  
Autoimmune Destruction ◽  
Glucose Dysregulation ◽  
Children And Young Adults ◽  
Remission Phase

Type 1 diabetes (T1D) is a metabolic disease of unknown aetiology that results from the autoimmune destruction of the β-cells. Clinical onset with classic hyperglycaemic symptoms occurs much more frequently in children and young adults, when less than 30% of β-cells remain. Exogenous insulin administration is the only treatment for patients. However, due to glucose dysregulation, severe complications develop gradually. Recently, an increase in T1D incidence has been reported worldwide, especially in children. Shortly after diagnosis, T1D patients often experience partial remission called “honeymoon phase,” which lasts a few months, with minor requirements of exogenous insulin. In this stage, the remaining β-cells are still able to produce enough insulin to reduce the administration of exogenous insulin. A recovery of immunological tolerance to β-cell autoantigens could explain the regeneration attempt in this remission phase. This mini-review focuses on the remission phase in childhood T1D. Understanding this period and finding those peripheral biomarkers that are signs of immunoregulation or islet regeneration could contribute to the identification of patients with a better glycaemic prognosis and a lower risk of secondary complications. This remission phase could be a good checkpoint for the administration of future immunotherapies.

scholarly journals Generation of pluripotent stem cells from patients with type 1 diabetes

2009 ◽  
Vol 106 (37) ◽  
pp. 15768-15773 ◽  
Author(s):  
René Maehr ◽  
Shuibing Chen ◽  
Melinda Snitow ◽  
Thomas Ludwig ◽  
Lisa Yagasaki ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Modeling ◽  
Ips Cells ◽  
Β Cells ◽  
Cell Replacement Therapy ◽  
Molecular Defects ◽  
Autoimmune Destruction ◽  
Induced Pluripotent ◽  
Adult Fibroblasts

Type 1 diabetes (T1D) is the result of an autoimmune destruction of pancreatic β cells. The cellular and molecular defects that cause the disease remain unknown. Pluripotent cells generated from patients with T1D would be useful for disease modeling. We show here that induced pluripotent stem (iPS) cells can be generated from patients with T1D by reprogramming their adult fibroblasts with three transcription factors (OCT4, SOX2, KLF4). T1D-specific iPS cells, termed DiPS cells, have the hallmarks of pluripotency and can be differentiated into insulin-producing cells. These results are a step toward using DiPS cells in T1D disease modeling, as well as for cell replacement therapy.

scholarly journals Transgenic overexpression of human Bcl-2 in islet β cells inhibits apoptosis but does not prevent autoimmune destruction

2000 ◽  
Vol 12 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Janette Allison ◽  
Helen Thomas ◽  
Dianne Beck ◽  
Jamie L. Brady ◽  
Andrew M. Lew ◽  
...  
Keyword(s):  
Β Cells ◽  
Autoimmune Destruction

scholarly journals Brakes on the accelerator: the journey of accelerator hypothesis from “the missing link” to “an evolving concept”

2017 ◽  
Vol 3 (12) ◽  
pp. 318
Author(s):  
Devi Dayal ◽  
Balasubramaniyan Muthuvel
Keyword(s):  
Alternative Mechanism ◽  
Β Cells ◽  
The Past ◽  
Autoimmune Destruction ◽  
Younger Age ◽  
Key Factor ◽  
Onset Of Diabetes ◽  
Accelerator Hypothesis

<p>The incidence of Type 1 diabetes (T1D) has increased significantly over the past few decades but the causes for this increase are poorly understood and hence the strategies for preventing T1D are difficult to design. T1D is characterised by autoimmune destruction of pancreatic β-cells resulting in insulin deficiency as opposed to Type 2 diabetes (T2D) characterised by weight driven insulin resistance (IR). The accelerator hypothesis (AH), proposed by the late Prof Terence Wilkin in 2001 offers an alternative mechanism for T1D and a different approach to prevention of T1D. This hypothesis considers both T1D and T2D as one and proposes that obesity driven IR is the key factor that may lead to either type of diabetes. It thus offers an easy explanation for the increasing worldwide incidence of childhood diabetes which is paralleled by the increase in childhood obesity rates. However, one of the key predictions of AH that the obesity related IR accelerates the onset of diabetes and hence heavier children should develop diabetes at a younger age, has remained a matter of debate since the hypothesis was first proposed. Since the inception of AH, the results of a number of studies which aimed at testing the hypothesis in diverse patient populations have shown support or opposed this key prediction. This article discusses the relevance of AH in the context of data from these studies.</p>

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