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Diagnostic contribution to the evaluation of intervention models in the treatment of type 1 diabetes
Zacharovová, Klára ; Saudek, František (advisor) ; Plecitá, Lydie (referee) ; Mandys, Václav (referee)
During treatment of diabetes mellitus by immunointervention or transplantation, it is necessary to monitor the markers of immune destruction or rejection of surviving insulin producing cells. An aim of this thesis is to improve the possibilities of following autoimmunity and to detect the survival of transplanted pancreatic islet in vivo. Partial aims included vitality testing of isolated islets for transplantation by measurement of respiration activity, observing the process of in vitro labeling of isolated islets with superparamagnetic iron oxide (SPIO) contrast agent for subsequent magnetic resonance imaging (MRI) of islets and observing SPIO particles transport after transplantation. We also studied a new dual paramagnetic contrast agent combined with fluorescein intended for identification of the MRI contrast agent in samples for histology. Further, we assessed autoimmune reaction by evaluation of cytokine response to specific stimulation with auto-antigens. We tried to affect beta-cells destruction by polyclonal anti- thymocyte antibodies in a mouse experimental model. A new method of the islet respiration measurement correlated with other methods of islet quality testing and it was suggested as a diagnostic test before clinical transplantation. Results obtained studying the intercellular...
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Molecular mechanism of insulin release
Tučková, Štěpánka ; Plecitá, Lydie (advisor) ; Bardová, Kristina (referee)
Insulin reduces glucose levels in blood and has impact on metabolism, cell- cycle and proliferation of target body cells. Its secretion from pancreatic β cells is induced right after food consumption, utilization in digestion system and nutrient elevation in blood circulation. Under physiological conditions molecular mechanisms include simultaneous effect of glucose, fatty acids, amino acids, ions, reactive oxygen species and neural and humoral system. The primary inducer is glucose, which is necessary also for insulin gene expression. Glucose modulates the fate of other nutrients, which enhance glucose stimulated insulin secretion. In general, glucose decreases fatty acid beta oxidation and increases the level of effector lipid intermediates in cytoplasm. The key processes within insulin release pathways are the Krebs cycle, pyruvate cycling and glycerole-3-phosphate/free fatty acids cycle. Moreover, endocrine signaling molecules, hormones and nervous system regulate insulin secretion through their receptors on β cell membranes. Disruption of regulatory mechanisms and insulin sensitivity of peripheral tissues may lead to development of diabetes mellitus.
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Diagnostic contribution to the evaluation of intervention models in the treatment of type 1 diabetes
Zacharovová, Klára ; Saudek, František (advisor) ; Plecitá, Lydie (referee) ; Mandys, Václav (referee)
During treatment of diabetes mellitus by immunointervention or transplantation, it is necessary to monitor the markers of immune destruction or rejection of surviving insulin producing cells. An aim of this thesis is to improve the possibilities of following autoimmunity and to detect the survival of transplanted pancreatic islet in vivo. Partial aims included vitality testing of isolated islets for transplantation by measurement of respiration activity, observing the process of in vitro labeling of isolated islets with superparamagnetic iron oxide (SPIO) contrast agent for subsequent magnetic resonance imaging (MRI) of islets and observing SPIO particles transport after transplantation. We also studied a new dual paramagnetic contrast agent combined with fluorescein intended for identification of the MRI contrast agent in samples for histology. Further, we assessed autoimmune reaction by evaluation of cytokine response to specific stimulation with auto-antigens. We tried to affect beta-cells destruction by polyclonal anti- thymocyte antibodies in a mouse experimental model. A new method of the islet respiration measurement correlated with other methods of islet quality testing and it was suggested as a diagnostic test before clinical transplantation. Results obtained studying the intercellular...
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