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Signalling of protein kinase B and expression of cyclooxygenase in early phases of diabetic nephropathy
Ždychová, Jana ; Komers, Radko (advisor) ; Haluzík, Martin (referee) ; Matoušovic, Karel (referee) ; Škrha, Jan (referee)
Introduction: Renal hypertrophy, extracellular matrix accumulation, aItered apoptosis as well as changes in regional hemodynamics have been implicated in the pathophysiology of nephropathy in diabetes mellitus (DM). On the molecular level the detailed mechanisms for development of diabetic nephropathy (DN) have becn intensively studied. Insulin induces a variety of biologicaI effects in a number of cell types via phosphatidylinositol-3 kinase (PI3K)/Akt kinase signaling pathway. Considering multiple function of Akt that incIude potentiaIly hannful pro-growth effects mediated by mTOR and cyclooxygenas-2 (COX-2), as well as protective effects mediated by endotheliaI nitric oxide synthase (eNOS), it is possible that aIterations in activities of Akt may play role in the pathophysiology ofDN. Renal corticaI activity and expression of Akt, its down-strearn effectors mTOR, eNOS, and "C<JIX-:Z. as well as PTEN, an endogenous Akt inhibitor, were investigated in streptozotocin (STZ): diabetic rats as a model of Type 1 DM with different levels of glycenůc control, and in Zucker ~d.iabetic fatty rats, a model ofDM2, and in nondiabetic rats as controls. Methods: Akt activity was measured by kinase assay. Protein expressions were measured by .immunoblotting and immunohistochemistry in renal cortex of 4- and 12- week old...
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Quantification of insulin secretion after administration of whey proteins in healthy subjects and in patients with type 2 diabetes
Wildová, Elena ; Anděl, Michal (advisor) ; Pelikánová, Terezie (referee) ; Škrha, Jan (referee)
INTRODUCTION: Milk and milk proteins have higher insulinogenic index than glycemic index. This feature is mainly attributed to whey proteins. The main goal of this thesis was to evaluate a C-peptide response after administration of whey proteins in healthy individuals (study 1) and in patients with type 2 diabetes mellitus (study 2) in comparison to other experimental stimulation tests. METHODS: Eight young, healthy (7 males, 1 female; aged 20-26 years), non-obese (BMI: 17 - 25.9 kg/mš) participants with normal glucose tolerance were enrolled for study 1. Each individual underwent six C-peptide secretion tests in total. Three secretion tests measured C-peptide response to orally administered substances: whey proteins only (OWT), whey proteins with glucose (OWGT) and glucose only (OGTT, reference); while the other three secretion tests measured C-peptide response to intravenously administered substances: arginine (AST), glucagon (GST) and glucose (IVGTT, reference). Sixteen overweight (BMI 26,4 - 29,8 kg/m2) patients with type 2 diabetes mellitus, good glycemic control and with preserved fasting serum C-peptide levels (0,94 ± 0, 07 nmol/l) were enrolled for study 2. Two oral stimulation tests - one with 75 g of glucose (OGTT) and the other with 75 g of whey proteins (OWIST) - were used for assessing...
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The role of nutritional therapist in education of patients with type 2 diabetes
Erban, David ; Škrha, Jan (advisor) ; Krátký, Jan (referee)
Aim of thesis: The research aimed to evaluate the importance of individual education by a clinical dietitian and compare it to information brochures only. Methods: 52 patients with type 2 diabetes from the Third Department of Internal Medicine of the General Hospital in Prague were selected for the research. Totally, 48 of them finished the research. These patients were divided into two groups. Group A was educated individually by a clinical dietitian. This group consisted of 27 patients, of which 13 were men and 14 were women. Group B was educated using a brochure only. This group consisted of 21 patients, of which 11 were men and 10 were women. Both groups were given the questionnaire before the education and then 4 months after the education. Additionally, glycated haemoglobin was measured in patients before the education and then 4 months after the education, during the next visit to their diabetologist. Results: In both groups, some improvement was observed after the education. Either in knowledge or their levels of glycated haemoglobin. In group A, the education had better cognitive results in all questions of the questionnaire except for one. Levels of glycated haemoglobin decreased by 9,4 in men and by 4,8 mmol/mol in women in group A. In group B, education did not affect the knowledge of...
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Effects of obesity on the course of Trypanosoma cruzi infection
Brima, Wunnie ; Zima, Tomáš (advisor) ; Šimánek, Vilím (referee) ; Škrha, Jan (referee)
Obesity is very widespread and detrimental to health. Obesity brings with it many changes including heightened immune function, and a higher prevalence of major cardiovascular disorders, cancer, diabetes, and Alzheimer disease. Obesity is also associated with shortened lifespan. The detrimental effects of obesity are linked to the "metabolic syndrome", a broad range of changes in metabolic processes and immune function. As a first approximation, we agree with this formulation but we will then proceed to document some of its weaknesses. (i) Crude mortality rates increase with increasing body mass index (BMI) but as the BMI approaches the normal range, mortality rates reverse (the now classic "J-shaped curve") so that individuals with reduced BMI have elevated mortality. (ii) A multiplicity of medical and surgical conditions have been reported where short term and medium term outcomes are better for overweight patients. These conditions are placed under the heading of "obesity paradox". (iii) The medical community has introduced a binary system for the metabolic syndrome ---- yes, patient has it or no, the patient does not have it, despite the fact that all of the changes that are considered components of the metabolic syndrome are continuous variables. Our work is focused on sharpening focus and improving...
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Quantification of insulin secretion after administration of whey proteins in healthy subjects and in patients with type 2 diabetes
Wildová, Elena ; Anděl, Michal (advisor) ; Pelikánová, Terezie (referee) ; Škrha, Jan (referee)
INTRODUCTION: Milk and milk proteins have higher insulinogenic index than glycemic index. This feature is mainly attributed to whey proteins. The main goal of this thesis was to evaluate a C-peptide response after administration of whey proteins in healthy individuals (study 1) and in patients with type 2 diabetes mellitus (study 2) in comparison to other experimental stimulation tests. METHODS: Eight young, healthy (7 males, 1 female; aged 20-26 years), non-obese (BMI: 17 - 25.9 kg/mš) participants with normal glucose tolerance were enrolled for study 1. Each individual underwent six C-peptide secretion tests in total. Three secretion tests measured C-peptide response to orally administered substances: whey proteins only (OWT), whey proteins with glucose (OWGT) and glucose only (OGTT, reference); while the other three secretion tests measured C-peptide response to intravenously administered substances: arginine (AST), glucagon (GST) and glucose (IVGTT, reference). Sixteen overweight (BMI 26,4 - 29,8 kg/m2) patients with type 2 diabetes mellitus, good glycemic control and with preserved fasting serum C-peptide levels (0,94 ± 0, 07 nmol/l) were enrolled for study 2. Two oral stimulation tests - one with 75 g of glucose (OGTT) and the other with 75 g of whey proteins (OWIST) - were used for assessing...
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The comparison of drinking regime of obese and non-obese type 2 diabetics
Görnerová, Lucie ; Vařeka, Tomáš (advisor) ; Škrha, Jan (referee)
This bachelor thesis is focused on topics of type 2 diabetes mellitus, obesity and drinking regime from the point of view of nutritional therapist. Objective of the bachelor thesis: Comparison of drinking regime in obese and non-obese type 2 diabetics. Methodology: The practical part of the bachelor thesis compares the drinking regime of obese and non-obese patients with type 2 diabetes. It monitors the quality and quantity of the proband drinking regime. There were 16 patients with type 2 diabetes approached in Diabetic Outpatient IV. of the VFN's internal clinic. 8 probands completed the research and their results are presented in the bachelor thesis. The participants filled out a form for seven days before and after the training seminar. They wrote down the quantity and type of drunk drinks. Prior to the training seminar, they filled out questionnaire number 1 focused on the patients' awareness about drinking regime in type 2 diabetes. After this seminar, they completed questionnaire number 2 examining the difficulty of monitoring compliance with this drinking regime. Questionnaire no. 2 tried to find out whether probands had thought about their drinking regime when putting it down and how they were motivated to take part in an educational seminar. Results: probands were divided into obese and...
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Pathobiochemistry of diabetes mellitus and its complications - oxidative stress, microinflammation and genetic predisposition.
Škrha, Jan ; Kalousová, Marta (advisor) ; Rybka, Jaroslav (referee) ; Bendlová, Běla (referee)
Diabetes is a chronic disease with high prevalence and significant morbidity. Chronic changes in the wall of small and large vessels lead to main diabetes complications. Apart from long- term hyperglycemia, several factors are involved in the development of diabetes vasculopathy. The aim of this work was to describe new early biomarkers of these vascular changes, to identify risky patients. Alongside, gene polymorphisms involved in protective pathways of glucose metabolism were studied. In three human studies with Type 1 (T1D) and Type 2 (T2D) diabetes patients special biochemical parameters of receptor for advanced glycation endproducts (RAGE) and its ligands, deglycation enzyme glyoxalase 1 (GLO1) and fructosamine 3-kinase (FN3K) gene polymorphisms were analyzed. Non-invasive measurement of glycation by skin autofluorescence (SAF) was assessed in all subjects. Soluble RAGE, HMGB1 and endothelial dysfunction markers were increased in patients with diabetes as compared with controls, however the differences between T1D and T2D were not significant. For the first time, an association between FN3K (rs1056534) and (rs3848403) polymorphism and sRAGE concentration in diabetes was shown. GLO1 (rs4746) polymorphism was associated with changes in endothelial dysfunction. Patients with diabetes had higher...
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Nutritional of patients with diabetes mellitus of the second type
Vlášková, Lenka ; Matoulek, Martin (advisor) ; Škrha, Jan (referee)
This bachelor thesis is focused on nutritional of patients with diabetes mellitus of the second type. The theoretical part defines type 2 diabetes mellitus. The incidence of type 2 diabetes mellitus has been increasing in our country and all over the world. Although the genetic predisposition is necessary for the development of diabetes, we can prevent this disease. The obesity as well as the other components of the metabolic syndrome prevention is very important in type 2 diabetes prevention. Physical activity is also very important, as it has a significant effect on insulin sensitivity and the dietary influences, which this bachelor thesis particularly deals with. The practical part is based on the survey, which contains the results of a questionnaire survey carried out at the 13rd International day of diabetes mellitus on Charles square in Prague. This part of the work shows how are their eating habits and activities. Keywords: diabetes mellitus, type 2 diabetes mellitus, diabetes, insulin resistance, obesity, metabolic syndrome, dietary prevention
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Effects of obesity on the course of Trypanosoma cruzi infection
Brima, Wunnie ; Zima, Tomáš (advisor) ; Šimánek, Vilím (referee) ; Škrha, Jan (referee)
Obesity is very widespread and detrimental to health. Obesity brings with it many changes including heightened immune function, and a higher prevalence of major cardiovascular disorders, cancer, diabetes, and Alzheimer disease. Obesity is also associated with shortened lifespan. The detrimental effects of obesity are linked to the "metabolic syndrome", a broad range of changes in metabolic processes and immune function. As a first approximation, we agree with this formulation but we will then proceed to document some of its weaknesses. (i) Crude mortality rates increase with increasing body mass index (BMI) but as the BMI approaches the normal range, mortality rates reverse (the now classic "J-shaped curve") so that individuals with reduced BMI have elevated mortality. (ii) A multiplicity of medical and surgical conditions have been reported where short term and medium term outcomes are better for overweight patients. These conditions are placed under the heading of "obesity paradox". (iii) The medical community has introduced a binary system for the metabolic syndrome ---- yes, patient has it or no, the patient does not have it, despite the fact that all of the changes that are considered components of the metabolic syndrome are continuous variables. Our work is focused on sharpening focus and improving...
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