scholarly journals Type I Diabetes-Associated Tolerogenic Properties of Interleukin-2

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Aziz Alami Chentoufi ◽  
Simon Gaudreau ◽  
Alex Nguyen ◽  
Mahmoud Sabha ◽  
Abdelaziz Amrani ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Type I Diabetes ◽  
Gene Knockout ◽  
Critical Role ◽  
Interleukin 2 ◽  
Nod Mice ◽  
Peripheral Tolerance ◽  
Type I ◽  
Tolerance Gene

Type 1 Diabetes (T1D) results from insulin-producing beta cells destruction by diabetogenic T lymphocytes in humans and nonobese diabetic (NOD) mice. The breakdown of tolerance has been associated with a defect in the number and the function of naturally occurring regulatory T cells (nTreg) that are the master player in peripheral tolerance. Gene knockout experiments in mouse models have shown a nonredundant activity of IL-2 related to its critical role in inducing nTreg and controlling peripheral T cell tolerance. Whereas strong evidence has suggested that IL-2 is critically required for nTreg-mediated T1D control, several fundamental questions remain to be addressed. In this paper, we highlight the recent findings and controversies regarding the tolerogenic properties of IL-2 mediated through nTreg. We further discuss a potential link between the immunomodulatory role of interleukin-2 and the pathogenesis of type 1 diabetes.

scholarly journals Health related quality of life among children with Type I diabetes, Assiut city, Egypt

2017 ◽  
Vol 7 (10) ◽  
pp. 73 ◽  
Author(s):  
Marzoka A. Gadallah ◽  
Taghreed Abdul-Aziz M. Ismail ◽  
Naglaa Saad Abdel Aty
Keyword(s):  
Quality Of Life ◽  
Type 1 Diabetes ◽  
Health Insurance ◽  
Type I Diabetes ◽  
Type I ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related

Objective: Health related quality of life (HRQOL) is a multidimensional construct that includes physical and psychosocial functioning, has emerged as an important outcome in pediatric population with chronic health conditions. The study objectives are to measure the quality of life among children with type I diabetes compared to healthy peers and to determine factors affecting the QOL among children with type I diabetes.Methods: Analytic cross sectional study was conducted in Sidi Galal health insurance outpatient clinic for children with type 1 diabetes mellitus and a comparison group of healthy peers was taken from other outpatient clinics. A total of four hundred and twelve children, aged from 8-18 years with type 1 diabetes and four hundred and twelve healthy peers matched in age and sex were interviewed. Three tools were used for this study: Demographic questionnaire, Socio-economic scale, and Peds QL4.0 Generic Core Scale was used to measure HRQOL.Results: The mean age of studied children was 12.9 ± 3.2. More than 60% of children with diabetes had uncontrolled glycemic level and 60% of them were in low socio-economic level. Children with diabetes had significantly lower HRQOL than healthy children in all domains. Age, glycemic control status and birth order of the diabetic children showed no significance difference regarding the QOL. Disease duration affected only the emotional function of the QOL and females showed significantly higher score regarding school functioning. Social, school and the total QOL scores were significantly higher among children with highly educated mothers while father's education affected the emotional, school and total QOL scores. Children in the middle and high social class showed significantly higher scores regarding social, school and total QOL. Presence of diabetic parent positively affected the social functioning while had negative effect on the school function of children with type I diabetes.Conclusions and recommendations: Diabetes is negatively affecting all the QOL functioning of the children. We recommend that Integrated programs between child's home, school and health insurance clinics for educating and supporting children with diabetes to improve their HRQOL.

scholarly journals Tissue-specific autoimmunity controlled by Aire in thymic and peripheral tolerance mechanisms

2019 ◽  
Vol 32 (2) ◽  
pp. 117-131
Author(s):  
Minoru Matsumoto ◽  
Koichi Tsuneyama ◽  
Junko Morimoto ◽  
Kazuyoshi Hosomichi ◽  
Mitsuru Matsumoto ◽  
...  
Keyword(s):  
T Cells ◽  
Type I Diabetes ◽  
Nod Mice ◽  
Peripheral Tolerance ◽  
Type I ◽  
Tolerance Mechanisms ◽  
Thymic Function ◽  
Tissue Specific ◽  
Thymic Stroma ◽  
Antigen Presenting

Abstract Tissue-specific autoimmune diseases are assumed to arise through malfunction of two checkpoints for immune tolerance: defective elimination of autoreactive T cells in the thymus and activation of these T cells by corresponding autoantigens in the periphery. However, evidence for this model and the outcome of such alterations in each or both of the tolerance mechanisms have not been sufficiently investigated. We studied these issues by expressing human AIRE (huAIRE) as a modifier of tolerance function in NOD mice wherein the defects of thymic and peripheral tolerance together cause type I diabetes (T1D). Additive huAIRE expression in the thymic stroma had no major impact on the production of diabetogenic T cells in the thymus. In contrast, huAIRE expression in peripheral antigen-presenting cells (APCs) rendered the mice resistant to T1D, while maintaining other tissue-specific autoimmune responses and antibody production against an exogenous protein antigen, because of the loss of Xcr1+ dendritic cells, an essential component for activating diabetogenic T cells in the periphery. These results contrast with our recent demonstration that huAIRE expression in both the thymic stroma and peripheral APCs resulted in the paradoxical development of muscle-specific autoimmunity. Our results reveal that tissue-specific autoimmunity is differentially controlled by a combination of thymic function and peripheral tolerance, which can be manipulated by expression of huAIRE/Aire in each or both of the tolerance mechanisms.

scholarly journals Causes of early-onset type 1 diabetes: toward data-driven environmental approaches

2008 ◽  
Vol 205 (13) ◽  
pp. 2953-2957 ◽  
Author(s):  
Pierre Bougnères ◽  
Alain-Jacques Valleron
Keyword(s):  
Type 1 Diabetes ◽  
Early Onset ◽  
Type I Diabetes ◽  
Metabolic Changes ◽  
Data Driven ◽  
Metabolic Phenotype ◽  
Type I ◽  
Β Cell ◽  
New Era

A new study reveals distinctive metabolic changes that precede the development of type 1 diabetes (T1D), tossing a stone into the quiet waters of T1D immunology and genetics. The causes of these metabolic changes and their relationship to autoimmunity and β cell destruction are not yet known, but the identification of a metabolic phenotype linked to susceptibility to type I diabetes may help pave the way to a new era of investigation of T1D causality.

Functional defects in adenylyl cyclase signaling mechanisms of insulin and relaxin in skeletal muscles of rat with streptozotocin type 1 diabetes

2006 ◽  
Vol 1 (4) ◽  
pp. 530-544 ◽  
Author(s):  
Alexander Shpakov ◽  
Ludmila Kuznetsova ◽  
Svetlana Plesneva ◽  
Alexander Kolychev ◽  
Vera Bondareva ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Adenylyl Cyclase ◽  
Skeletal Muscles ◽  
Glycogen Synthase ◽  
Type I Diabetes ◽  
Functional Coupling ◽  
Type I ◽  
Stimulatory Action ◽  
Functional Disturbance

AbstractFunctional disturbance in the novel adenylyl cyclase signaling mechanism (ACSM) of insulin and relaxin action in rat streptozotocin (STZ) type I diabetes was studied on the basis of the authors’ conception of molecular defects in hormonal signaling systems as the main causes of endocrine diseases. Studying the functional state of molecular components of the ACSM and the mechanism as a whole, the following changes were found in the skeletal muscles of diabetic rats compared with control animals: 1) increase of insulin receptor binding due to an increase in the number of insulin binding sites with high and low affinity; 2) increase of the basal adenylyl cyclase (AC) activity and the reduction of AC-activating effect of non-hormonal agents (guanine nucleotides, sodium fluoride, forskolin); 3) reduction of ACSM response to stimulatory action of insulin and relaxin; 4) decrease of the insulin-activating effect on the key enzymes of carbohydrate metabolism, glycogen synthase and glucose-6-phosphate dehydrogenase. Hence, the functional activity of GTP-binding protein of stimulatory type, AC and their functional coupling are decreased during experimental type 1 diabetes that leads to the impairment of the transduction of insulin and relaxin signals via ACSM.

scholarly journals Increased Circulating T Follicular Helper Cells in Iranian Children with Type I Diabetes

2019 ◽  
Author(s):  
Mansour Arab ◽  
Maryam Razzaghy-azar ◽  
Zahra Salehi ◽  
Maryam Keshavarz ◽  
Ensieh Nasli-Esfahani ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Autoimmune Disease ◽  
Type I Diabetes ◽  
Type I ◽  
T Follicular Helper Cells ◽  
Helper Cells ◽  
Follicular Helper ◽  
Iranian Children

Type 1 diabetes (T1D) is an autoimmune disease resulting from the damage of pancreatic

New approach for in vivo detection of insulitis in type I diabetes: activated lymphocyte targeting with 123I-labelled interleukin 2

1994 ◽  
Vol 131 (4) ◽  
pp. 431-437 ◽  
Author(s):  
Alberto Signore ◽  
Marco Chianelli ◽  
Elisabetta Ferretti ◽  
Anna Toscano ◽  
Keith E Britton ◽  
...  
Keyword(s):  
Gamma Camera ◽  
Type I Diabetes ◽  
Interleukin 2 ◽  
Nod Mice ◽  
Insulin Dependent Diabetes ◽  
Type I ◽  
New Approach ◽  
In Vivo Detection ◽  
Insulin Dependent

Signore A, Chianelli M, Ferretti E, Toscano A, Britton KE, Andreani D, Gale EAM, Pozzilli P. New approach for in vivo detection of insulitis in type I diabetes: activated lymphocyte targeting with 123I-labelled interleukin 2. Eur J Endocrinol 1994;131:431–7. ISSN 0804–4643 Insulitis is considered the histopathological hallmark of type I (insulin-dependent) diabetes. In the nonobese diabetic (NOD) mouse, diabetes has never been observed in the absence of insulitis. The in vivo detection of insulitis could be of relevance for early prediction of diabetes. As approximately 15% of islet-infiltrating lymphocytes express interleukin 2 receptors, we have labelled recombinant interleukin 2 with 123I and used this radiopharmaceutical to detect insulitis by gamma camera imaging. We studied 71 prediabetic NOD and 27 normal Balb/c mice. Labelled α-lactalbumin was used as the control protein. In the first set of experiments we studied the tissue distribution of radiolabelled interleukin 2 in isolated organs from animals sacrificed at different time points. Higher radioactivity was detected in the pancreas of NOD mice injected with labelled interleukin 2, as compared to NOD mice receiving labelled α-lactalbumin (p < 0.003 at 20 min; p< 0.001 at 40 min; p< 0.0001 at 60 min) or Balb/c mice injected with labelled interleukin 2 (p< 0.05 at 40 min; p< 0.001 at 60 min). In another set of experiments, gamma camera images have been acquired after injection of 123I-labelled interleukin 2. Radioactivity in the pancreatic region of prediabetic NOD and Balb/c mice showed similar kinetics to those observed by single organ counting, with higher accumulation in the pancreatic region of NOD mice (p < 0.04 after 22–45 min in NOD mice vs Balb/c mice). Finally, a positive correlation was found between the radioactivity in the pancreas and the extent of lymphocytic infiltration (p < 0.01 for pancreas radioactivity counted in vitro and p< 0.004 for pancreas radioactivity counted in vivo by gamma camera). This study demonstrates that 123I-labelled interleukin 2 administered iv accumulates specifically in the inflamed pancreas of diabetes-prone NOD mice, suggesting its potential application in human insulin-dependent diabetes mellitus. A Signore, Servizio Speciale di Medicina Nucleare, II Clinica Medica, Policlinico Umberto I, 00161 Roma, Italy

Kinetics of sodium-lithium countertransport activity in patients with uncomplicated type I diabetes

1992 ◽  
Vol 82 (3) ◽  
pp. 291-299 ◽  
Author(s):  
Peter A. Rutherford ◽  
Trevor H. Thomas ◽  
Susan J. Carr ◽  
Roy Taylor ◽  
Robert Wllklnson
Keyword(s):  
Type 1 Diabetes ◽  
Essential Hypertension ◽  
Type I Diabetes ◽  
Plasma Lipid ◽  
Maximum Velocity ◽  
Diabetic Patients ◽  
Type I ◽  
High Sodium ◽  
Type 1 Diabetic Patients

1. Increased erythrocyte sodium-lithium countertransport activity has been reported to be associated with nephropathy in type 1 diabetes and linked to a family history of essential hypertension. 2. This study aimed to determine the mechanism of increased sodium-lithium countertransport activity. Sodium-lithium countertransport kinetics were measured in uncomplicated and hyperlipidaemic type 1 diabetic patients. 3. In the nine out of 31 uncomplicated type 1 diabetic patients who had high sodium-lithium countertransport activity, the sodium affinity (Km) was normal but the maximum velocity (Vmax.) was increased. 4. Hyperlipidaemia, when present in diabetic patients, was associated with increased sodium-lithium countertransport activity, but could not explain the high activity in uncomplicated type 1 diabetic patients in whom plasma lipid concentrations were normal. 5. Sodium-lithium countertransport activity is increased in type 1 diabetes by a mechanism different to that in essential hypertension, where the mechanism is a low Km (increased sodium affinity). Hence familial hypertension cannot explain the raised sodium-lithium countertransport activity in type 1 diabetes.

scholarly journals Type I Diabetes Mellitus: Genetic Factors and Presumptive Enteroviral Etiology or Protection

2014 ◽  
Vol 2014 ◽  
pp. 1-21 ◽  
Author(s):  
Jana Precechtelova ◽  
Maria Borsanyiova ◽  
Sona Sarmirova ◽  
Shubhada Bopegamage
Keyword(s):  
Type 1 Diabetes ◽  
Inflammatory Diseases ◽  
Type I Diabetes ◽  
Oral Route ◽  
Basic Knowledge ◽  
Type I ◽  
Human Pathogens ◽  
Genetic Components ◽  
Chronic Myocarditis

We review type 1 diabetes and host genetic components, as well as epigenetics and viruses associated with type 1 diabetes, with added emphasis on the enteroviruses, which are often associated with triggering the disease. GenusEnterovirusis classified into twelve species of which seven (Enterovirus A, Enterovirus B, Enterovirus C,andEnterovirus DandRhinovirus A, Rhinovirus B,andRhinovirus C) are human pathogens. These viruses are transmitted mainly by the fecal-oral route; they may also spread via the nasopharyngeal route. Enterovirus infections are highly prevalent, but these infections are usually subclinical or cause a mild flu-like illness. However, infections caused by enteroviruses can sometimes be serious, with manifestations of meningoencephalitis, paralysis, myocarditis, and in neonates a fulminant sepsis-like syndrome. These viruses are often implicated in chronic (inflammatory) diseases as chronic myocarditis, chronic pancreatitis, and type 1 diabetes. In this review we discuss the currently suggested mechanisms involved in the viral induction of type 1 diabetes. We recapitulate current basic knowledge and definitions.

scholarly journals Correction of dyslipidemia with combined use of beta-sitosterol and polyprenyl phosphates in dogs with type 1 diabetes mellitus

2019 ◽  
Vol 2019 (5) ◽  
pp. 12-15
Author(s):  
Вячеслав Анников ◽  
Vyacheslav Annikov ◽  
Александр Наровлянский ◽  
Aleksandr Narovlyanskiy ◽  
Александр Санин ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Type I Diabetes ◽  
Control Group ◽  
Type I ◽  
Upper Limit ◽  
Combined Use ◽  
Polyprenyl Phosphates

This study considers the efficiency of use of a combined drug based on beta-sitosterol and polyprenyl phosphates in dogs with type I diabetes mellitus complicated by hyperlipidemia. It was shown that after 1 month of the therapy, there was a significant decrease of the level of cholesterol, triglycerides and glucose vs. control animals. After 2 months of the therapy, in the control group the level of cholesterol and triglycerides was at the upper limit of the norm, which can lead to an exacerbation of the disease in future.

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