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Functional genomic and pharmacogenomic analysis of metabolic syndrome aspects
Krupková, Michaela ; Šeda, Ondřej (advisor) ; Haluzík, Martin (referee) ; Polák, Jan (referee)
Metabolic syndrome is a prevalent disease characterized by concurrent manifestation of insulin resistance, obesity, dyslipidemia, hypertension and other hemodynamic and metabolic disorders. It has multifactorial type of inheritance and its resultant phenotype is determined by both environmental and genetic factors as well as their interactions. That is the main reason why comprehensive analysis of the genetic component of this syndrome is complicated in human population. Genetically designed experimental animal models are significant tools for analysis of genetic architecture of human complex conditions including the metabolic syndrome. The aim of this Thesis is utilization of functional and comparative genomic tools to uncover pathogenesis of metabolic syndrome aspects and their genetic determinants. We also studied pharmacogenetic interactions of these genetic determinants with drugs affecting particular components of the metabolic syndrome. Establishing and utilizing several genetically designed congenic rat strains, we undertook four different research projects focusing on pharmacogenetic interaction of all-trans retinoic acid and ondansetron with differential segment of rat chromosome 8, pharmacogenetic interaction of differential segment of rat chromosome 4 and dexamethasone, determining Plzf...
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Pharmacological modifications of potential signal systems regulating metabolism of adipocytes and hepatocytes and their influence on obesity
Hodis, Jiří ; Farghali, Hassan (advisor) ; Kršiak, Miloslav (referee) ; Otová, Berta (referee)
v anglickém jazyce: Thesis abstract: Background and aims: Both obesity and metabolic syndrome form severe health problems in the whole world. Nevertheless the armament of pharmacotherapy for both diseases remains unsatisfactory. We aimed our work to main organs in risk of the mentioned diseases -liver and visceral fat using hepatocytes and visceral adipocytes as model. We detected 3 main metabolic and signalization activities- glycogenolysis, Nitric oxide (NO) production and transcription of inducible NO synthase (iNOS) in hepatocytes, lipolysis, NO production and iNOS transcription rate in adipocytes. We directed our interest to combination of peroxisome proliferation activator receptor γ (PPARγ) agonist, antagonist and β3 adrenergic agonist in the culture of epididymal rat adipocytes in the first part of our work. While in the second part we investigated the influence of β and α adrenergic mimetics, adrenergic blockers in the culture of rat high glycogen content hepatocytes. Methods: NO production was detected under the active agents treatments by detection of NO oxidative products NO2 and NO3 in media. Glycogenolysis was measured as free glucose rise released by hepatocytes into the media. NOS transcription level was extrapolated after comparative polymerase chain reaction with reverse...
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Insulin Resistance and Metabolic inFlexibility : the Influence of Renin Angiotensin System Inhibition
Wohl, Petr ; Pelikánová, Terezie (advisor) ; Prázný, Martin (referee) ; Vondra, Karel (referee)
Insulin resistance (IR) is considered to be an important factor influencing the progression of atherosclerosis and is associated with higher morbidity and mortality. IR is a common feature of diabetes mellitus Type 2 and obesity. Many authors consider IR being the crucial abnormality of the metabolic syndrome which is characterized by the essential hypertension, hyperliproteinemia, visceral obesity, endothel dysfunction and many other abnormalities. Impaired insulin action (IR) is also described in diabetes mellitus Type 1, however this phenomenon has not been fully explained. The subjects of dissertation thesis was directed on the IR importance in diabetic Type 1 patients as well as on the renin angiotensin system inhibition in patients with IR and metabolic syndrome with impaired glucose homeostasis. Hyperinsulinemic euglycemic clamp is used in combination with indirect calorimetry to estimate the IR in vivo in humans. In our project we focused on a) the existence of the metabolic inflexibility phenomenon in type 1 diabetic patients b) the methodological evaluation of the hyperinsulinemic euglycemic clamp procedure in the same group c) the influence of renin angiotensin system inhibition with angiotensin II type 1 receptor inhibitor telmisartan in patients with metabolic syndrome and impaired glucose...
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The analysis of mechanisms associated with beneficial metabolic effects of marine Omega-3 polyunsaturated fatty acids in different lipid forms.
Pavlišová, Jana ; Rossmeisl, Martin (advisor) ; Maletínská, Lenka (referee) ; Cahová, Monika (referee)
Obesity, one of the most serious health problems of the 21st century, often occurs as a result of an imbalance between energy intake and energy expenditure. Dietary lipids play an important role in the development of obesity, partly because they represent the richest source of energy amongst all macronutrients. It is, however, not only the amount of consumed lipids, but also the composition of fatty acids, which strongly influences health effects of a particular diet. Saturated fatty acids (SFA) are generally considered as unhealthy due to their pro-inflammatory and lipotoxic properties, while monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) represent a healthier alternative, as they are more readily oxidized and do not disrupt biochemical properties of cellular membranes. Amongst PUFA, PUFA of n-3 series (Omega-3) represent an utterly unique class of lipids that have been documented to protect against cardiovascular disease and dyslipidemia in men and improve insulin sensitivity and glucose tolerance primarily in animal models of obesity. Some molecular mechanisms of Omega-3 action have been already uncovered, such as the modification of biological membranes composition, activation of various transcription factors and membrane receptors, and their role as precursors for...
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Gestational diabetes diet
Kuchařová, Miroslava ; Krejčí, Hana (advisor) ; Anderlová, Kateřina (referee)
The Master's thesis entitled "Gestational Diabetes Diet" deals with the issue of eating habits and a lifestyle of women diagnosed with gestational diabetes mellitus during pregnancy. The theoretical part of the thesis describes the definition, causes and a mechanism of origin, consequences for mother and fetus and also deals with the diagnostic procedures and all possibilities of treatment of this disease. In this part, the diagnostic method analyzed by using the oGTT stress test and a diabetic diet - that together with other preventive measures (mainly physical aktivity) is the first choice in the treatment of pregnancy diabetes - are described in more details. The practical part of this master's thesis contains the results of a questionnaire survey in two groups of pregnant women - with already diagnosed gestational diabetes and before its diagnosis in the oGTT test. It also contains the results of the analysis of women with GDM diets. The analysis were processed by the NutriPro Expert diet program and the results are then compared with the current nutritional recommendations of the Czech Republic for pregnant and nursing women. The aim of this work was to map the eating habits and lifestyle of women with gestational diabetes and find out whether they meet current nutritional recommendations or...
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Relation among BMI, hyperinsulinemia and selected biochemical indicators
Dobrovodová, Monika ; Kovařík, Miroslav (advisor) ; Herink, Josef (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Student: Monika Dobrovodová Supervisor of master thesis: PharmDr. Miroslav Kovařík, Ph.D. Advisor of master thesis: prof. MUDr. Karel Martiník, DrSc. Title of master thesis: Relation among BMI, hyperinsulinemia and selected biochemical indicators This thesis is focussed on specification of relations among BMI, insulinemia, age of the patients, C-peptid blood levels and glycemia and also searching relations among selected parameters of lipid spectrum in group of selected patients. Measuring of body height and weight and investigation of fasting glycemia, insulinemia, total cholesterolemia, blood levels of HDL and LDL and also C-peptid were done at 3472 patients. Afterwards few basic indexes of insulin resistance and sensitivity were counted. In this group was proven, that fasting insulinemia and C-peptid levels are increasing in according to increasing BMI. Also fasting glycemia is increasing modestly. Insulin resistance and sensitivity indexes used in this theses depends on BMI. Although statistically significant differences between age groups were proven according to insulin resistance and sensitivity indexes, we can't see clearly increasing or decreasing tendency in according to...
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The food intake comparison of the patients with the metabolic syndrome with or without hepatosteatosis/steatohepatitis
Štičková, Zdeňka ; Macášek, Jaroslav (advisor) ; Meisnerová, Eva (referee)
The aim of this bachelor thesis is to compare the food intake in patients with metabolic syndrome, who suffer from non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). The main aim of this bachelor thesis is to find out differences in the diet of different groups of patients comprising patients with simple obesity, patients with metabolic syndrome without steatosis, patients with metabolic syndrome with steatosis and patients with metabolic syndrome complicated by steatohepatitis. This thesis is divided into two parts - theoretical and practical. The theoretical part introduces metabolic syndrome, its definition, occurrence, etiology, complications and its prevention and treatment. The topics about pathophysiology of the liver and the definition of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis are also covered. Methods: The practical part is a quantitative research in the form of questionnaires made at the 4th Internal Department at the General University Hospital in Prague. The patients met the criteria of the mentioned symptoms or diseases. The thesis compares the data from literature with the responses of the patients. We explored the question of the diet composed for example by regular intake of fermented milk products, selenium, green tea or...
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The use of magnetic resonance spectroscopy for studying glucose metabolism
Kratochvílová, Simona ; Pelikánová, Terezie (advisor) ; Štich, Vladimír (referee) ; Polák, Jan (referee)
Magnetic resonance spectroscopy (MRS) is a noninvasive technique that enables to follow metabolic processes in selected tissues in vivo. Recently the attention has been focused on metabolic mapping in target organs of insulin action to describe the pathophysiology of insulin resistance. The aim of our study was to present the practical application of ³¹P (phosphorus) MRS and ¹H (proton) MRS in metabolic studies of skeletal muscle in insulin resistant subjects and in subjects with impaired fasting glucose. The third study was aimed to evaluate the brain metabolism with ¹H MRS in healthy controls and subjects with type 1 diabetes during hyperinsulinemia. ¹H and ³¹P MRS were performed using a MR Scanner Siemens Vision operating at 1,5 Tesla. To assess the parameters of glucose metabolism and insulin action oral glucose tolerance test and hyperinsulinemic euglycemic clamp were performed. The study 1 was aimed to evaluate the skeletal muscle (m. soleus) energetic metabolism in the offspring of hypertensive parents (OH) with a higher level of insulin resistance. The concentrations of selected high energy phosphates (phosphocreatine, inorganic phosphate, adenosintriphosphate, phosphomonoesters, phosphodiesters) were evaluated with ³¹P MRS. Their amount in OH was comparable to healthy controls. However we...
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Insulin resistance and postprandial state in type 2 diabetes. The effect of meal frequency and composition on glucose metabolism and other manifestations of the metabolic syndrome
Thieme, Lenka ; Pelikánová, Terezie (advisor) ; Kunešová, Marie (referee) ; Šmahelová, Alena (referee)
The project focuses on dietary interventions in type 2 diabetes(T2D). The aim was to investigate how glucose metabolism and other manifestations of insulin resistance should be influenced by a) the composition of macronutrients and b) frequency of meals; and to characterize the possible mechanisms of these dietary interventions in patients with T2D. A. In a randomized crossover study, 50 patients T2D and 50 age-matched healthy subjects underwent in a random order meal tolerance tests with three isocaloric meals (vegan sandwich; V-meal, hamburger; M-meal, or cheese sandwich; S-meal. Blood samples for analysis were taken at time 0 and after 30, 60, 120 and 180 minutes after meal ingestion. Plasma concentrations of plasma glucose, insulin, C-peptide, lipids, oxidative stress markers and gastrointestinal hormones (GIHs) were investigated. Both basal and postprandial plasma concentrations of glucose and insulin were significantly higher in patients with T2D (p<0.001); basal and postprandial concentrations of almost all other GIHs (except for ghrelin) and thiobarbituric acid reactive substances (TBARS) were significantly increased (p<0.001), while ascorbic acid, reduced glutathione and superoxide dismutase activity were decreased in patients with T2D compared to healthy controls (p<0.001). The meal rich...
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