scholarly journals N-Acetyl-l-Cysteine Supplement in Early Life or Adulthood Reduces Progression of Diabetes in Nonobese Diabetic Mice

2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Lital Argaev Frenkel ◽  
Hava Rozenfeld ◽  
Konstantin Rozenberg ◽  
Sanford R Sampson ◽  
Tovit Rosenzweig
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Type 1 Diabetes ◽  
Antioxidant Enzymes ◽  
Early Life ◽  
Nod Mice ◽  
Morbidity Rate ◽  
Nonobese Diabetic ◽  
Total Antioxidant

ABSTRACT Background Oxidative stress contributes to the pathologic process leading to the development, progression, and complications of type 1 diabetes (T1D). Objective The aim of this study was to investigate the effect of the antioxidant N-acetyl-l-cysteine (NAC), supplemented during early life or adulthood on the development of T1D. Methods NAC was administered to nonobese diabetic (NOD) female mice during pregnancy and lactation, and the development of diabetes was followed in offspring. In an additional set of experiments, offspring of untreated mice were given NAC during adulthood, and the development of T1D was followed. Morbidity rate, insulitis and serum cytokines were measured in the 2 sets of experiments. In addition, markers of oxidative stress, glutathione, lipid peroxidation, total antioxidant capacity and activity of antioxidant enzymes, were followed. Results Morbidity rate was reduced in both treatment protocols. A decrease in interferon γ, tumor necrosis factor α, interleukin 1α, and other type 1 diabetes-associated proinflammatory cytokines was found in mice supplemented with NAC in adulthood or during early life compared with control NOD mice. The severity of insulitis was higher in control NOD mice than in treated groups. NAC administration significantly reduced oxidative stress, as determined by reduced lipid peroxidation and increased total antioxidant capacity in serum and pancreas of mice treated in early life or in adulthood and increased pancreatic glutathione when administrated in adulthood. The activity of antioxidant enzymes was not affected in mice given NAC in adulthood, whereas an increase in the activity of superoxide dismutase and catalase was demonstrated in the pancreas of their offspring. Conclusion NAC decreased morbidity of NOD mice by attenuating the immune response, presumably by eliminating oxidative stress, and might be beneficial in reducing morbidity rates of T1D in high-risk individuals.

scholarly journals Rodent Models for Investigating the Dysregulation of Immune Responses in Type 1 Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Feng-Cheng Chou ◽  
Heng-Yi Chen ◽  
Shyi-Jou Chen ◽  
Mei-Cho Fang ◽  
Huey-Kang Sytwu
Keyword(s):  
Type 1 Diabetes ◽  
Animal Studies ◽  
Genetic Manipulation ◽  
Nod Mice ◽  
Environmental Parameters ◽  
Conditional Knockout ◽  
Therapeutic Approaches ◽  
Nonobese Diabetic ◽  
Genetically Manipulated

Type 1 diabetes (T1D) is an autoimmune disease mediated by T cells that selectively destroy the insulin-producingβcells. Previous reports based on epidemiological and animal studies have demonstrated that both genetic factors and environmental parameters can either promote or attenuate the progression of autoimmunity. In recent decades, several inbred rodent strains that spontaneously develop diabetes have been applied to the investigation of the pathogenesis of T1D. Because the genetic manipulation of mice is well developed (transgenic, knockout, and conditional knockout/transgenic), most studies are performed using the nonobese diabetic (NOD) mouse model. This paper will focus on the use of genetically manipulated NOD mice to explore the pathogenesis of T1D and to develop potential therapeutic approaches.

scholarly journals Genetic and functional data identifying Cd101 as a type 1 diabetes (T1D) susceptibility gene in nonobese diabetic (NOD) mice

PLoS Genetics ◽  
2019 ◽  
Vol 15 (6) ◽  
pp. e1008178 ◽  
Author(s):  
Jochen Mattner ◽  
Javid P. Mohammed ◽  
Michael E. Fusakio ◽  
Claudia Giessler ◽  
Carl-Philipp Hackstein ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Functional Data ◽  
Susceptibility Gene ◽  
Nod Mice ◽  
Nonobese Diabetic

scholarly journals Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Susanne W. Bruun ◽  
Knud Josefsen ◽  
Julia T. Tanassi ◽  
Aleš Marek ◽  
Martin H. F. Pedersen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cells ◽  
Degradation Products ◽  
Intestinal Barrier ◽  
Nod Mice ◽  
Radioactive Label ◽  
Nonobese Diabetic ◽  
Gliadin Peptide ◽  
Gliadin Peptides

Gluten promotes type 1 diabetes in nonobese diabetic (NOD) mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin secretion from beta cells directly. We hypothesized that gluten fragments may cross the intestinal barrier to be distributed to organs other than the gut. If present in pancreas, gliadin could interact directly with the immune system and the beta cells to initiate diabetes development. We orally and intravenously administered 33-mer and 19-mer gliadin peptide to NOD, BALB/c, and C57BL/6 mice and found that the peptides readily crossed the intestinal barrier in all strains. Several degradation products were found in the pancreas by mass spectroscopy. Notably, the exocrine pancreas incorporated large amounts of radioactive label shortly after administration of the peptides. The study demonstrates that, even in normal animals, large gliadin fragments can reach the pancreas. If applicable to humans, the increased gut permeability in prediabetes and type 1 diabetes patients could expose beta cells directly to gliadin fragments. Here they could initiate inflammation and induce beta cell stress and thus contribute to the development of type 1 diabetes.

scholarly journals Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Xue-Song Zhang ◽  
Jackie Li ◽  
Kimberly A Krautkramer ◽  
Michelle Badri ◽  
Thomas Battaglia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 1 Diabetes ◽  
Early Life ◽  
System Development ◽  
Nod Mice ◽  
Intestinal Microbiome ◽  
Host Immune System ◽  
Intestinal Immunity ◽  
Immune System Development

The early-life intestinal microbiota plays a key role in shaping host immune system development. We found that a single early-life antibiotic course (1PAT) accelerated type 1 diabetes (T1D) development in male NOD mice. The single course had deep and persistent effects on the intestinal microbiome, leading to altered cecal, hepatic, and serum metabolites. The exposure elicited sex-specific effects on chromatin states in the ileum and liver and perturbed ileal gene expression, altering normal maturational patterns. The global signature changes included specific genes controlling both innate and adaptive immunity. Microbiome analysis revealed four taxa each that potentially protect against or accelerate T1D onset, that were linked in a network model to specific differences in ileal gene expression. This simplified animal model reveals multiple potential pathways to understand pathogenesis by which early-life gut microbiome perturbations alter a global suite of intestinal responses, contributing to the accelerated and enhanced T1D development.

scholarly journals Lipid Peroxidation and Antioxidant Status in Male and Female Patients with Type 1 and Type 2 Diabetes Mellitus

Med Phoenix ◽  
2017 ◽  
Vol 1 (1) ◽  
pp. 10-14
Author(s):  
Nirjala Laxmi Madhikarmi ◽  
Prem Prakash Singh ◽  
Tarannum Khatun
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Lipid Peroxidation ◽  
Antioxidant Status ◽  
Total Antioxidant Activity ◽  
Male And Female ◽  
Total Antioxidant

Background: Free radicals are reactive oxygen species which cause lipid peroxidation precipitating many metabolic diseases including Diabetes Mellitus. However, these free radicals are quenched by substances known as antioxidants like vitamin C, vitamin E and several other compounds. Lipid peroxidation and antioxidant status were investigated in patients with Type 1 and Type 2 Diabetes mellitus- Pokhara, Nepal.Methods: The extent of lipid peroxidation was assessed by thiobarbituric acid reactive substances and the antioxidant parameter estimations were total antioxidant activity, Vitamin C and Vitamin E assessed in Type 1 and 2 diabetes mellitus patients along with matched healthy counterparts.Results: The lipid peroxidation was increased in male Type 1 and 2 diabetic patients whereas female group showed decreased level as compared to its healthy counterparts. Similarly, the total antioxidant activity was found to be decreased in the diabetic group. The lipid peroxidation parameter and antioxidant status were statistically significant at p< 0.05.Conclusion: Oxidative stress and antioxidant status varied in male and female patients suffering from diabetes either Type 1 or Type 2. Apart from gender basis of evaluating oxidative stress, variables based on diet, habitat, socioeconomic status, education, etc. can also be considered.MED Phoenix Volume (1), Issue (1) July 2016, page: 10-14

scholarly journals Efficacy and Safety of Resveratrol in Type 1 Diabetes Patients: A Two-Month Preliminary Exploratory Trial

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 161 ◽  
Author(s):  
Ali Movahed ◽  
Pema Raj ◽  
Iraj Nabipour ◽  
Marzieh Mahmoodi ◽  
Afshin Ostovar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 1 Diabetes ◽  
Cell Function ◽  
Preliminary Investigation ◽  
Resveratrol Treatment ◽  
Total Antioxidant ◽  
Β Cell Function ◽  
Liver And Kidney ◽  
Baseline Values

Resveratrol has been reported to be beneficial against diabetes complications. The objective of this study was to evaluate the efficacy of resveratrol in decreasing hyperglycemia in patients with type 1 diabetes (T1D) by a preliminary investigation designed as an exploratory clinical trial. Thirteen patients with T1D from both the sexes participated in this trial. All patients received resveratrol in 500 mg capsules, twice daily for 60 days. Bodyweight, fasting blood sugar (FBS), hemoglobin A1c (HbA1c), insulin, homeostasis model of assessment for insulin resistance (HOMA-IR), homeostasis model of assessment for β-cell function (HOMA-β), and markers of liver and kidney damage, inflammation, and oxidative stress were measured before the intervention, at 30 days and at 60 days. Resveratrol supplementation for 60 days significantly decreased FBS and HbA1c in comparison with the baseline values. Resveratrol treatment also resulted in a decrease in the level of a marker for oxidative stress, malondialdehyde, and an increase in total antioxidant capacity in T1D patients. Insulin, HOMA-IR, HOMA-β, and markers of liver and kidney function and inflammation were not significantly affected by resveratrol treatment. Overall, the results showed that 60 days of resveratrol supplementation exerted strong antidiabetic and antioxidant effects in patients with T1D.

The biochemical effects of occupational exposure to lead and cadmium on markers of oxidative stress and antioxidant enzymes activity in the blood of glazers in tile industry

2018 ◽  
Vol 34 (7) ◽  
pp. 459-467 ◽  
Author(s):  
Maryam Hormozi ◽  
Ramazan Mirzaei ◽  
Alireza Nakhaee ◽  
Shahrokh Izadi ◽  
Javid Dehghan Haghighi
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Antioxidant Enzymes ◽  
Occupational Exposure ◽  
Control Group ◽  
Blood Levels ◽  
Biochemical Effects ◽  
Lead And Cadmium ◽  
Total Antioxidant ◽  
Markers Of Oxidative Stress

The aim of the present study was to evaluate the effects of occupational exposure to lead (Pb) and cadmium (Cd) on markers of oxidative stress in glazers in tile industries. Total antioxidant capacity (TAC), malondialdehyde (MDA), and the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined in the blood of 80 subjects, including 40 glazers and 40 nonexposed subjects. Mean levels of blood Cd (8.90 ± 2.80 µg/L) and blood Pb (62.90 ± 38.10 µg/L) of glazers showed a significant increase compared with the control group. In the serum of glazers, the level of MDA was significantly higher and the level of TAC was significantly lower than the control group. We have noted a disturbance in the levels of antioxidants by a significant increase in the CAT activity and a significant decrease in the activities of SOD and GPx in the serum of glazers compared with the controls. Correlation analysis demonstrated that the serum MDA level and CAT activity were positively associated with the blood levels of Pb and Cd. Also, GPx and SOD were negatively correlated with blood Cd levels. The study clearly indicated that co-exposure to Cd and Pb can induce oxidative stress in glazers, resulting in increased lipid peroxidation and altered antioxidant enzymes.

scholarly journals Systemic Delivery of TNF-Related Apoptosis-Inducing Ligand (TRAIL) Elevates Levels of Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) and Prevents Type 1 Diabetes in Nonobese Diabetic Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (12) ◽  
pp. 5638-5646 ◽  
Author(s):  
Soojeong Kang ◽  
Eun-Jin Park ◽  
Yeonsoo Joe ◽  
Eunhui Seo ◽  
Mi-Kyoung Park ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Blood Glucose ◽  
Gelatin Zymography ◽  
Nod Mice ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitor ◽  
Nonobese Diabetic ◽  
Induced Apoptosis

Recent studies have demonstrated that TNF-related apoptosis-inducing ligand (TRAIL) is a modulator of the immune response. The relation between TRAIL and type 1 diabetes (T1D) as an autoimmune inflammatory disease in vivo is relatively unknown. To explore the potential role of TRAIL in the development of T1D, we examined its in vivo effects in nonobese diabetic (NOD) mice. NOD mice at 7 wk of age were iv injected with an adenovirus carrying either human TRAIL (Ad.hTRAIL) or β-galactosidase genes. Blood glucose was monitored weekly, and the expression of hTRAIL was evaluated in plasma and liver of mice. To investigate whether hTRAIL elicits its effect through the induction of tissue inhibitor of metalloproteinase-1 (TIMP-1), we examined the concentration of plasma TIMP-1 by ELISA and the inhibition of matrix metalloproteinase (MMP) by gelatin zymography. Here, we show that Ad.hTRAIL-transduced mice had significantly reduced blood glucose levels and markedly increased production of TIMP-1 compared with control β-galactosidase animals. Pancreatic tissue isolated from Ad.hTRAIL-treated NOD mice showed reduced MMP activities associated with significantly improved insulitis. In addition, TIMP-1 in vitro suppressed cytokine-induced apoptosis in insulin-producing INS-1 cells. These results indicate that T1D can be prevented by TRAIL overexpression through enhancement of TIMP-1 function. Elevated TIMP-1 production inhibits the activity of MMPs, which may contribute to suppress the transmigration of diabetogenic T cells into the pancreatic islets and protects pancreatic β-cells from cytokine-induced apoptosis. Therefore, TRAIL and TIMP-1 induction may be potential targets to prevent development of T1D.

scholarly journals Prevention of type 1 diabetes in mice by tolerogenic vaccination with a strong agonist insulin mimetope

2011 ◽  
Vol 208 (7) ◽  
pp. 1501-1510 ◽  
Author(s):  
Carolin Daniel ◽  
Benno Weigmann ◽  
Roderick Bronson ◽  
Harald von Boehmer
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Nod Mice ◽  
Nonobese Diabetic ◽  
Cell Clones ◽  
Autoimmune Attack ◽  
Agonistic Activity ◽  
Novel Strategy

Type 1 diabetes (T1D) results from the destruction of insulin-secreting pancreatic β cells by autoreactive T cells. Insulin is an essential target of the autoimmune attack. Insulin epitopes recognized by diabetogenic T cell clones bind poorly to the class II I-Ag7 molecules of nonobese diabetic (NOD) mice, which results in weak agonistic activity of the peptide MHC complex. Here, we describe a strongly agonistic insulin mimetope that effectively converts naive T cells into Foxp3+ regulatory T cells in vivo, thereby completely preventing T1D in NOD mice. In contrast, natural insulin epitopes are ineffective. Subimmunogenic vaccination with strongly agonistic insulin mimetopes might represent a novel strategy to prevent T1D in humans at risk for the disease.

scholarly journals Immunomodulator Drug (IMODTM) and Exercise Improve Cardiac Oxidative Stress and Antioxidant Balance in Diabetic Rats

2020 ◽  
Vol 15 (3) ◽  
Author(s):  
Ali Ali-Aghdam ◽  
Elham Karimi-Sales ◽  
Javad Mahmoudi ◽  
Rafigheh Ghiasi ◽  
Mohammad Reza Alipour
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Cardiac Injury ◽  
Diabetic Rats ◽  
Oxidative Stress Marker ◽  
Positive Effects ◽  
Total Antioxidant ◽  
Immunomodulatory Drug ◽  
First Time

: Diabetes is a common metabolic disease that increases the risk of cardiovascular disease. It seems that the reduction of oxidative stress or increasing antioxidant levels improves diabetic cardiomyopathy. Antioxidant effects of immunomodulatory drug (IMODTM) and also beneficial influences of exercise on diabetic complications have been shown. The present study examined the effects of IMODTM and exercise on cardiac oxidative stress and antioxidants in diabetes. For this purpose, 64 rats were divided into 8 groups: control (C), exercise (E), IMODTM (20 mg/kg) (I), exercise plus IMODTM (E + I), diabetes (D), diabetic rats treated with exercise (D + E), diabetic rats treated with IMODTM (D + I), and diabetic rats treated with exercise plus IMODTM (D + E + I). Treatments with exercise and/or IMODTM were performed for 8 weeks. Type 1 diabetes was induced by intraperitoneal injection of 60 mg/kg streptozotocin. After the treatment period, all rats were anesthetized, and blood and heart samples were gathered for measurement of malondialdehyde (MDA) as an oxidative stress marker, lactate dehydrogenase (LDH) as a cardiac injury marker, total antioxidant capacity (TAC), and superoxide dismutase (SOD) as well as glutathione peroxidase (GPx) as antioxidant enzymes. The present study, for the first time, showed that IMODTM alone or in combination with exercise had positive effects on alleviating hyperglycemia, MDA, and LDH along with elevation of antioxidant enzymes activities in type 1 diabetic rats.

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