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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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Mechanisms underlying the development of insulin resistance in liver steatosis
Papáčková, Zuzana ; Cahová, Monika (advisor) ; Macek Jílková, Zuzana (referee)
We tested the hypothesis that triacylglycerol (TAG) accumulation in the liver induced by short-term high-fat diet (HFD) in rats leads to the dysregulation of endogenous TAG degradation via lysosomal pathway and is causally linked with the development of hepatic insulin resistance. Lysosomal lipase (LAL) is stored in qualitatively different depots (light and dense lysosomes). In contrast to dense lysosomal fraction, LAL associated with light lysosomes exhibits high activity on intracellular TAG and prandial- or diet-dependent regulation. On standard diet, LAL activity was up-regulated in starved and down-regulated in fed animals. In the HFD group, we demonstrated elevated LAL activity, increased TAG content, enhanced production of diacylglycerol and the abolishment of prandial-dependent LAL regulation in light lysosomal fraction. The impairment of insulin signalling and increased activation of PKCε was found in liver of HFD-fed animals. Lipolysis of intracellular TAG, mediated by LAL, is increased in steatosis probably due to the enhanced formation of phagolysosomes. Consequent overproduction of diacylglycerol may represent the causal link between HFD-induced hepatic TAG accumulation and hepatic insulin resistance via PKCε activation.
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Metabolic effects of chronic metformin administration in obese mice depending on the composition of high-fat diet
Roubalová, Jana ; Rossmeisl, Martin (advisor) ; Vybíral, Stanislav (referee)
Obesity leads to many severe metabolic disorders, e.g. dyslipidemia, insulin resistance, ectopic fat accumulation in the liver and skeletal muscles, non-alcoholic fatty liver disease and finally diabetes mellitus type 2. Metformin (1,1-dimethylbiguanide) is the most favored medicament for the treatment and prevention of these disorders. It stimulates cellular glucose uptake and normalizes blood levels of lipid metabolites without triggering insulin secretion. Research on insulin resistance and diabetes is often realized through developing diet- induced obesity in laboratory animals. The aim of this project is to compare metabolic effects of two different high-fat diets named HFD and HSD. The HFD diet consists chiefly of n-6 polyunsaturated fatty acids (corn oil) and starch (100% glucose). The HSD diet contains mainly saturated fatty acids (lard) and sucrose (50% glucose and 50% fructose). I also studied metabolic effects of metformin by adding it continuously to the drinking water given to obese mice fed with the HFD or the HSD diet. Methods: Intraperitoneal glucose tolerance test (IPGTT), blood and tissue levels of lipid metabolites assessment, radio-immunological assessment of blood levels of insulin, assessment of AMPK activity in liver by western blotting. Results: Increased consumption of the...
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Depression and Insulin Resistance
Hess, Zdeněk ; Rosolová, Hana (advisor) ; Šimon, Jaroslav (referee) ; Souček, Miroslav (referee) ; Beran, Jiří (referee)
Introduction: Metabolic syndrome and depression are considered to be important risk factors for the development of cardiovascular diseases. The prevalence of metabolic syndrome is estimated to be around 25% of the adult population in industrialized countries, including the population of Czech Republic. The prevalence of depression is estimated to be around 15% of the same adult population. It is not clear yet on the base of poor literature, which is so far available, whether there is a causal relationship between these factors or not. Objective: To try to find a relationship between metabolic syndrome and depression in a population sample using clinical and metabolic parameters. Methods: The prevalence of depressivity or other psychopathologies was evaluated with the use of self-report questionnaires in a randomly selected population sample of 259 people living in Pilsen. The questionnaires were mailed to the subjects. Those of them who responded were invited to the examination of anthropometric and laboratory parameters defining the metabolic syndrome and to the examination of some other parameters. The occurrence of risk factors of the metabolic syndrome of insulin resistance and the relationship between depression and metabolic syndrome was investigated. Metabolic syndrome of insulin resistance...
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The role of protein kinase C in the pathogenesis of insulin resistance and its complications
Marková, Irena ; Novák, František (advisor) ; Zeman, Miroslav (referee) ; Zídková, Jarmila (referee)
18 effects of TZDs are probably due to the remodeling of adipose tissue and increased adiponectin secretion. SUMMARY Studying the pathogenesis of insulin resistance and the role of PKC in insulin resistance In HHTg rats, elevated serum triglycerides and FFA were associated with the ectopic accumulation of triglycerides in tissues and reduced insulin sensitivity of peripheral tissues. Impaired glucose utilization in the peripheral tissues was associated with the reduced activity of GS in skeletal muscle. Decreased GS activity and glucose utilization in peripheral tissues indicate a possible defect in insulin signal transduction. In line with this, our results show that skeletal muscle IR was associated with the increased activation and translocation of PKC θ. Nutritionally induced obesity of HHTg rats resulted, in many cases, in the further deterioration of metabolic abnormalities associated with IR. We found that PKC θ, in particular, could contribute to the metabolic abnormalities associated with IR and obesity. The age-related increase in IR and deterioration of some parametres of carbohydrate and lipid metabolism, were not associated, in HHTg rats, with obesity but with increased serum levels of triglycerides and FFA. The age-related worsening of IR in HHTg rats was accompanied by increased...
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Design and verification of the intervention program for client with metabolic syndrome visiting Wellbeing Centre VŠTJ MEDICÍNA in České Budějovice
BENÝŠKOVÁ, Ivetta
Presented personal case study shows the effects of targeted intervention motion drawn up the plan and verifying its functionality for clients with severe metabolic syndrome. The client is a 39-year old obese (BMI of 32.3, height 164 cm, weight 87 kg) diabetic. Emphasis was placed on the program-controlled weight reduction exercise. The client for 13 weeks completed 53 hours of physical activity of aerobic and weight training character in 46 training units. The results confirm the success of case reports targeted exercise intervention in the therapy of obesity and metabolic syndrome. Significantly decreased the value of glycated hemoglobin, waist circumference shrank by 5 cm, total weight reduction amounted to 2 kg. Within three months, an improvement in client anthropometric, biochemical and cardiovascular indicators.
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Effect of exercise intervention in patients with type 2 DM on selected physiological parameters.
ŠVENDOVÁ, Marcela
This diploma thesis focuses on the topic: "Influence of Exercise Intervention on Selected Physiological Parameters of Patients with DM Type 2." In the theoretical part, the main concepts are characterized - physical activity and inactivity, prevention, health, and civilisation diseases. From the civilization diseases, the issue of diabetes mellitus type 2 is substantially developed. In the practical part, the effect of physical activity, particularly walking 3 times a week for 60 min with low to medium loads, on selected anthropometric, biochemical, and physiological parameters is described in detail. The thesis compares an experimental group of 10 women and 10 men in the age of 45-60 years with a control group of 10 women and 10 men of the same age. The experiment was designed to be performed for three months from 09/2015 to 11/2015 and at the end the initial and final data on weight, waist circumference, blood pressure, glycaemia on an empty stomach, postprandial glycaemia, and glycated haemoglobin were compared.
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Dietary habits and lifestyle in metabolic syndrome
TOMANOVÁ, Gabriela
ABSTRACT Title of the work: Eating habits and a lifestyle by metabolic syndrome This bachelor thesis deals with the eating habits and the lifestyle in patients with metabolic syndrome treated in diabetologic clinics. The work is divided into two main parts. The first (theoretical) part deals with the existing and newly discovered knowledge in the area of this issue, the eating habits and lifestyle. Primarily, I studied the issue and changes in MS. In the initial chapter I mention the main components and consequently I deal with most discussed changes in the recent years. The last specified part deals with the factors affecting the MS; here,I have been concerned with the most important categories, including eating habits, physical activity, smoking, genetics and stress. The second part (empirical) should clarify the problems in complying with good eating habits and lifestyle. It should prove the correctness and effectiveness of education in persons showing symptoms of MS. The work was designed as a quantitative research in which the target file was constituted by a selected sample of 120 respondents showing MS in diabetologic clinics. To obtain the necessary information, a questionnaire survey was used. The research confirmed a relatively good education and eating habits in patients with MS. During questioning it was found that 77% of respondents claim to have a sufficient amount of information and good eating habits. But a deeper examination of their dietary habits revealed that only 67% of them actually know how to eat properly. On the other hand, 23% of the observed patients lack of the information from a doctor, therefore they cannot have good eating habits. A positive result is that two thirds of patients educated in the diabetologic clinics are really able to eat properly and work with the information they receive. Unfortunately, the remaining 10% have enough information from their doctor, but they cannot work with the information so as to achieve the correction of dietary habits. A part of this bachelor thesis forms a health educational material that is destined for patients who do not have enough information or those who are familiar with the issue, but are interested to learn more.
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