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Nutritional Factors in Skeletal Muscle Insulin Resistance Development
Gojda, Jan ; Anděl, Michal (advisor) ; Saudek, František (referee) ; Prázný, Martin (referee)
Nutritional Factors in Skeletal Muscle Insulin Resistance Development Jan Gojda Abstract Background. Diet composition ranks among etiological factors of insulin resistance (IR) and diabetes. Vegans, people consuming exclusively plant-based diet, have significantly lower prevalence of IR and thus represent a suitable model population for study of nutritional factors on IR development. Branched chain amino acids (BCAA) ranks among these factors. Aims and hypothesis. Aim of the observational study was to prove that vegans have better glucoregulatory functions and thus to validate "vegan vs. omnivore" model. Aim of the consecutive interventional study was to prove in this model that dietary intervention with BCAA leads to a group sepcific changes in the insulin function mesures. Methods. 11 vegans and 10 omnivorous controls were recruited in the observational study. Hyperinsulinemic euglycemic clamp (HEC) and muscle (SM) biopsies (amount of intramyocellular lipids (IMCL), mtDNA and the activity of citrate synthase (CS)) were performed. 8 vegans and 8 omnivores were consequently subjected to the intervention with 15 or 20 g of BCAA respectively. The examination was performed at the baseline, after the intervention and after 6 months wash-out period: anthropometry, HEC, arginine test, SM biopsy (CS, activity of...
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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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Physiologic and pathophysiologic aspects of selected endocrinopathies. Their relationship to adipose tissue matebolism and insulin resistance
Ďurovcová, Viktória ; Kršek, Michal (advisor) ; Saudek, František (referee) ; Štich, Vladimír (referee)
The pathogenesis of insulin resistance is a complex and still intensively studied issue. Endocrine and paracrine activity of the adipose tissue together with mi- tochondrial dysfunction are the most discussed potential factors included in the development of insulin resistance. In the first part of our study we examined the involvement of the adipose tissue and its secretory products in the etiopathogenesis of insulin resistance in patients with Cushing's syndrome, acromegaly and simple obesity. We focused on three important regulators of metabolic homeostasis - fibroblast growth factors 21 and 19 (FGF-21 and FGF-19) and adipocyte fatty acid binding protein (FABP-4). We found significantly elevated circulating levels of FGF-21 and FABP-4 ac- companying insulin resistance in both patients with simple obesity and patients with obesity connected to Cushing's syndrome, as compared to healthy controls. The concentrations of both substances were comparable between hypercortisolic and obese patients. This finding together with the absence of correlation be- tween the levels of FGF-21 resp. FABP-4 and cortisol suggest that the reason for elevation of their concentrations is obesity and its metabolic consequences themselves rather then the effect of hypercortisolism on FGF-21 and FABP-4 production. We found no...
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Differentiation of adult stem cells into insulin-producing beta cells
Koblas, Tomáš ; Saudek, František (advisor) ; Grim, Miloš (referee) ; Štechová, Kateřina (referee)
Ph.D. Thesis abstract: Diabetes mellitus is a chronic disease characterized by a metabolic disorder in which there is a low level or complete lack of the insulin. Diabetes mellitus type 1 (DM1) is caused by an autoimmune reaction leading to the destruction of the insulin producing beta cells in the pancreas. In consequence, low or non-existent insulin production leads to a complete dependence on exogenous insulin supplementation. DM1 causes serious long-term complications. Although strict control of blood sugar could prevent the onset and development of diabetic complications only 5% of diabetic patients are able to achieve such control. Hence it is evident that the current methods of treatment are neither sufficient to treat this disease, nor prevent late complications in most patients. The most promising therapeutic approach in the treatment of diabetes is the restoring of insulin production. One such method is the transplantation of insulin-producing tissue. However, a lack of available insulin- producing tissue limits such therapeutic approach. Therefore an alternative source of insulin producing cells have to be found to obtain a sufficient amount of safe and efficient insulin producing tissue. Pancreatic stem/progenitor cells could represent such an available alternative source. Despite the evidence...
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BK-polyomavirus infection in patients after simultaneous pancreas and kidney transplantation
Mindlová, Martina ; Saudek, František (advisor) ; Forstová, Jitka (referee) ; Reischig, Tomáš (referee)
Introduction. The aim of the study was to introduce a new BKV PCR protocol in our centre and to verify its accuracy as well as to assess the prevalence, risk factors of BK virus replication, course of BKV infection and therapeutic approaches in simultaneous pancreas and kidney (SPK) recipients in order to design a screening protocol. Methods. The results analysed by both Affigene® and Transplantation Virology, Basel PCR protocols were compared. Thereafter 183 SPK patients were examined to assess the prevalence of BK viremia, viruria and BKVN and to identify the risk factors of BKV replication. The cases of retransplantation after a graft loss due to BKVN were retrospectively described. Results. 100 of results were analysed according to the Affigene ® and Transplantation Virology, Basel PCR protocols with the accordance of 95%, Rho = 0,946, 95% CI: 0.920 - 0.963, P<0,0001, Bland-Altman plot analyses: bias Basel PCR protocol/Affigene® BKV trender: -0,1 (mean) *±1.96 SD: -1,6 - 1,3] for both methods. Point-prevalence was assessed in 183 patients; Viruria found in 17,3 %, viremia in 3.8% of patients. High-level viruria >107 copies/mL detected in 3,7% of patiets, high-level virémia >104 in 1,6% of patients simultaneously with high-level viruria. BKVN was found in 0,5% of patients. Diabetes duration...
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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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Nursing care of the patient treated by the pancreatic islets transplantation
Bobek, Vít ; Heřmanová, Jana (advisor) ; Saudek, František (referee)
Cílem mojí bakaláská práce je nastínit klinické a zejména ošetovatelské aspekty pée o pacienta podstupujícího zatím ponkud nezvyklý zpsob léby diabetu 1. typu - transplantaci Langerhansových ostrvk. Práce se zamuje na lébu diabetu 1. typu s labilním prbhem. Jako píklad sleduji pacienta, který v nedávné dob s úspchem podstoupil tento nový zpsob léby. V klinické ásti popisuji strun historii poznávání diabetu, endokrinní funkci pankreatu a pak etiopatogenezi, imunogenetiku, klinický obraz, diagnostiku, a terapii diabetu 1. typu a jeho komplikací. Dále popisuji specifika labilní formy tohoto onemocnní a možnosti léebné intervence. V ošetovatelské ásti analyzuji prostednictvím ošetovatelského modelu Marjory Gordonové poteby pacienta podstupujícího takový výkon. Vytváím plán pée a popisuji jeho realizaci v samotný den provedení transplantace Langerhansových ostrvk. Dále zde eším problematiku dlouhodobé pée, edukace a psychosociálního obrazu pacienta.
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Labeling of pancreatic islets with superparamagnetic iron oxide nanoparticles for magnetic resonance imaging
Berková, Zuzana ; Saudek, František (advisor) ; Mandys, Václav (referee) ; Haluzík, Martin (referee)
Type I diabetes mellitus is primarily an autoimmune disease resulting from selective destruction of insulin producing pancreatic beta cells. Transplantation of purified pancreatic islets is an alternative method for standard insulin therapy of these patients. Though the islet transplantation represents a promising approach for a selected group of patients, there is still a number of problems to be solved and one of them, perhaps the most important, is the lack of a reliable method of transplanted islets monitoring. (...) The results of this experimental study lead to the improvement of the labeling protocol in experimental transplantation and to its translation into clinical research. While different methods such as PET and SPECT will be soon available for shorttime in vivo followup of transplanted pancreatic islet, magnetic resonance imaging represents so far the only available technique able to provide a direct, longterm and reliable visualization of the transplanted islets with sufficient spatial resolution. At present, is this method ready for clinical application.
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