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Immunointerventional therapy of autoimmune diabetes with recent oncet in NOD mice.
Vargová, Lenka ; Saudek, František (advisor) ; Štechová, Kateřina (referee) ; Mráz, Miloš (referee)
Introduction: Type 1 diabetes mellitus is a chronic metabolic disease caused by autoimmune destruction of pancreatic beta cells. The theory of the disease onset is derived from study of a disease course in non-obese diabetic (NOD) mice, in which the diabetes occurs due to a dysregulation of the immune system. Experimental and clinical studies showed that the autoimmunity may be abrogated by immune intervention, which if initiated early enough may at least slow down the ongoing beta cells lost and preserve residual insulin secretion. But immune intervention alone is not sufficient to restore normoglycemia in the majority of cases. Several interventional studies showed that stimulation of proliferation and/or regeneration of beta cells are necessary to restore normoglycemia in animal models. Aim of the study: To find out, if the combination of a potent immunosuppression (murine anti-thymocyte globulin (mATG), gusperimus) together with stimulation of islet regeneration (sitagliptin) will be able to slow down or reverse the course of the disease. Another aim is to identify the mechanism by which the substances act. Material and methods: All experiments were performed in female NODShiLtJ (H2g7 ) mice. The following parameters were examined at day 0, 7, 14 and 28: blood glucose, subpopulations of...
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Effect of gluten-free diet on immune cell subsets in the NOD mouse model of type 1 diabetes
Tejklová, Tereza ; Funda, David (advisor) ; Krulová, Magdaléna (referee)
Type 1 diabetes (T1D) is an autoimmune disease leading to destruction of insulin-secreting pancreatic -cells. Environmental factors e.g. exposures to infections, dietary components play a substantial role in etiopathogenesis of T1D and are responsible for rapid increase of T1D incidence in past decades, preferentially in developed countries. Despite long record of T1D research no causative cure or efficient prevention exists. While gluten displays proinflammatory properties, gluten-free diet (GFD) has been documented by several studies as a strong diabetes- preventive environmental factor in spontaneous animal models of T1D, mostly in NOD mouse. The aim of this thesis is to better characterize effects of GFD on the immune system of NOD mouse. Using flow cytometry, we compared effects of GFD vs standard (STD) Altromin diets on NK cell subsets, Tregs, as well as other regulatory cell subsets and their cytokine profile in prediabetic SPF NOD females that were exposed to the diets since "in utero". A reference diabetes incidence in NOD females in our SPF facility kept on STD and GFD was recorded. Diabetes-preventive capacity of GFD were tested by using the NOD-SCID model of diabetes transfer, in which splenocytes from at-onset NOD females kept on GFD or STD were transferred to NOD-SCID recipients....
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Effect of gluten-free diet on potentially regulatory immune mechanisms in human type 1 diabetes
Císařová, Radka ; Funda, David (advisor) ; Zadražil, Zdeněk (referee)
Type 1 diabetes (T1D) is an autoimmune disease, whose incidence is rising every year, and its prevention or a cure does not exist. T1D is influenced by multiple genetic factors but environmental factors represent the major contributor to the recent almost epidemic increase of T1D incidence worldwide, primarily in developed countries. Amongst these factors belong for example enteroviral infections, microbiota dysbiosis or gluten-free diet (GFD). GFD has been proven to have a protective effect in NOD mice, which is a spontaneous model of T1D, and a beneficial effect on glycemic control in humans, when administered after T1D onset. This diploma thesis examined changes of regulatory and potentially regulatory T-cells and their cytokines in peripheral blood mononuclear cells (PBMC) of T1D children, who underwent 12-month intervention trial of GFD. Secondly, the thesis assessed if the influence of GFD on immune regulatory functions can be transferred by colonization of germ-free NOD mice with gut microbiota of these children. We have found that intervention with GFD increases percentage of Tr1 cells and IL-10 producing CD4+ T-cells in PBMC of T1D children. Furthermore, the beneficial effect on immune regulation can be at least partially transferred to NOD mice by the colonization with human microbiota...
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Dietary factors in the development of type 1 diabetes
Fiala, Marek ; Funda, David (advisor) ; Grobárová, Valéria (referee)
Type 1 diabetes mellitus is an autoimmune disease which develops in genetically susceptible individuals and whose incidence rapidly increases, especially in developed countries. Type 1 diabetes is believed to be strongly associated with the environment: viruses, stressful life events or the absence of exposition to antigens in early life increase its incidence. Antigens to which we are expressed continuously are food antigens. Gluten, milk proteins or the intake of vitamin D precursors clearly influence type 1 diabetes pathogenic process. This bachelor's thesis aims to describe our current knowledge on the role of dietary factors in type 1 diabetes, their possible immune mechanisms and also interplay with other environmental factors. Key words: type 1 diabetes, dietary factors, gluten-free diet, immune mechanisms, prevention, NOD mouse, mucosal immunity
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Immunointerventional therapy of autoimmune diabetes with recent oncet in NOD mice.
Vargová, Lenka ; Saudek, František (advisor) ; Štechová, Kateřina (referee) ; Mráz, Miloš (referee)
Introduction: Type 1 diabetes mellitus is a chronic metabolic disease caused by autoimmune destruction of pancreatic beta cells. The theory of the disease onset is derived from study of a disease course in non-obese diabetic (NOD) mice, in which the diabetes occurs due to a dysregulation of the immune system. Experimental and clinical studies showed that the autoimmunity may be abrogated by immune intervention, which if initiated early enough may at least slow down the ongoing beta cells lost and preserve residual insulin secretion. But immune intervention alone is not sufficient to restore normoglycemia in the majority of cases. Several interventional studies showed that stimulation of proliferation and/or regeneration of beta cells are necessary to restore normoglycemia in animal models. Aim of the study: To find out, if the combination of a potent immunosuppression (murine anti-thymocyte globulin (mATG), gusperimus) together with stimulation of islet regeneration (sitagliptin) will be able to slow down or reverse the course of the disease. Another aim is to identify the mechanism by which the substances act. Material and methods: All experiments were performed in female NODShiLtJ (H2g7 ) mice. The following parameters were examined at day 0, 7, 14 and 28: blood glucose, subpopulations of...
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