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Strategies and results in the development of insulin derivatives for the treatment of diabetes
Pokorný, Štěpán ; Jiráček, Jiří (advisor) ; Hlouchová, Klára (referee)
The aim of this bachelor's thesis is to present insulin analogs and to analyse the direction of development of these organic compounds. The text contains basic information on this subject (e.g. the history of Diabetes Mellitus, the first treatment, the discovery of insulin (1921) and the experiments that preceded this discovery...). The thesis also explains the basic differences between type 1 and type 2 Diabetes Mellitus and the resulting differences in treatment. It mainly summarizes, the specific types of analogs, their chemical composition and the nature of their action. The main contribution of this work lies in the analysis of insulin analogs and the overview of the course in which the development of these analogues is proceeding or what innovations we can expect in diabetes therapy in the upcoming years. The thesis draws primarily from peer-reviewed scientific papers, articles and books (older as well as more recent ones) and from the expertise of the IOCB laboratory. All sources are well cited at the end of the work.
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The role of orexins in food intake and chosen pathological phenomena
Zelená, Anna ; Sumová, Alena (advisor) ; Balounová, Kateřina (referee)
Orexins are neuropeptides produced in the lateral hypothalamus in the brain and peripheral organs. These neuropeptides are essential in regulating arousal and energy balance. They also participate in the reward system and secure water homeostasis. Orexins bind to the orexin receptors differently expressed in various tissues. The binding of orexins to their receptors couples with downstream signalling pathways, e.g., Ca2+ , diacylglycerol and protein kinase C pathways. Low concentration of adenosine triphosphate leads to the inactivation of orexin-expressing neurons and the reduction of energy expenditure. On the contrary, high intracellular concertation of adenosine triphosphate activates energy expenditure. Food intake is regulated by orexins and glucose, sirtuin 1, forkhead box transcription factor 2, and leptin. This thesis aims to find connections between the role of orexins in regulating food intake and the development of some pathological phenomena, e.g., hypertension, obesity, and anorexia nervosa. Keywords orexin, obesity, anorexia nervosa, glucose, insulin, stress
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Targeting insulin storage forms in pancreatic β-cell secretory granules
Asai, Seiya ; Jiráček, Jiří (advisor) ; Skořepa, Ondřej (referee) ; Koblas, Tomáš (referee)
In this dissertation, we focused on a comprehensive investigation of insulin production, storage and secretion by pancreatic -cells. We successfully developed a new assay for the rapid and sensitive determination of insulin concentration in biological samples. This assay, based on the competition of the measured sample with a radioligand for the insulin receptor, helped us to determine the influence of several low molecular weight compounds, as well as peptides, on insulin secretion. We found that arginine and ornithine have a dose-dependent stimulatory effect on glucose- stimulated insulin secretion from -cells, but that dopamine inhibits insulin secretion. The effect of serotonin on insulin secretion was ambiguous. We also studied the effects of the bone protein osteocalcin and its fragments on insulin secretion. We found that these peptides do not stimulate insulin secretion from -cells, but that osteocalcin may have proliferative properties. We also tested the effect of tryptophan and its metabolites and found that these compounds do not stimulate insulin secretion but that some of them may inhibit secretion at higher concentrations. An important result of the study is the experimental confirmation of the presence of crystalline insulin in the secretory granules of -cells. This is the first...
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Preparation and characterization of vesiculin, a two-chain protein derived from IGF-2
Mrzílková, Karolína ; Žáková, Lenka (advisor) ; Pačesová, Andrea (referee)
Hormones of insulin family are one of the most studied groups of proteins due to their connection to large number of diseases including type two diabetes mellitus, tumorigenesis and some neurodegenerative diseases. The newest member of this superfamily is a two-chain analogue of IGF-2 called vesiculin. This peptide was originally isolated from secretory granules of mouse βTC6-F7 cell line and is currently believed to have a endocrine or paracrine effect on pancreatic β-cells. Its sequence homology with IGF-2 and structural similarity to insulin foreshadows vesiculin's potential metabolic, proliferation and growth properties and further secures its place as scientifically interesting and clinically lucrative topic. The insulin theme is corelated with insulin resistance, pathological state present primarily in early stages of development of type two diabetes mellitus. Vesiculin is able to stimulate glucose uptake and glycogen synthesis even in this condition which differentiates it form insulin and IGF-2 whose glucoregulatory activity is blunted in face of insulin resistance. Further research of vesiculin and insulin family receptor interaction, including dimeric tyrosinekinase receptor for IGF-1 and insulin, but also monomeric IGF-2 receptor, can provide more knowledge on character of this binding...
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Effect of nutritional intervention on compensation of diabetes mellitus type 2 in patients treated with insulin
Hes, Filip ; Flekač, Milan (advisor) ; Pehr, Martin (referee)
Introduction: The topic of the bachelor's thesis is ,,Effect of nutritional intervention on the compensation of type 2 diabetes mellitus in patients treated with insulin". Diabetes mellitus is a chronic civilization disease, the incidence increases every year. Nutritional education of patients is one of the effective ways to help better compensation of diabetes. Aim of thesis: The aim of the work was to determine the effect of individual nutritional education on the compensation of T2DM in patients treated with an intensified insulin regimem. Methods: For the research were selected 14 patients with T2DM who are treated with intensified insulin therapy. These patients are visiting the Third Department of Internal Medicine of the General Hospital in Prague. All patients completed the study. They were divided into two groups. Group A was individually educated. Group B patients served as the control group. Glycated hemoglobin results were recorded at the beginning of the study and after approximately three months at the next follow-up with a diabetologist. Results: An improvement in glycated hemoglobin values was observed in the group individually educated group compared to the control group. At the same time, education had a positive effect on answers to most questions related to diabetes. In group A,...
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Role of Arginine 717 in insulin receptor respective Arginine 704 in IGF-1 receptor for the interaction with ligands
Kertisová, Anna ; Selicharová, Irena (advisor) ; Ryšlavá, Helena (referee)
Insulin and insulin-like growth factor 1 (IGF-1) are peptide hormones that are important regulators of cellular metabolism, proliferation and apoptosis. Disruptions in signalling pathways may cause a whole range of diseases from diabetes mellitus type 1 and type 2 to cancer or neurodegenerative diseases. The cellular response to these hormones is mediated by insulin (IR) and IGF-1 receptors (IGF-1R) with a tyrosin-kinase activity. Receptors are created as hetero-tetramers of two extracellular α-subunits and two intracellular β-subunits. Studies of receptor structures try to elucidate the basic principles of the interaction of receptors with their ligands. However, the role of some amino-acid residues in binding remains unclear. It was suggested that the arginine 704 of IGF-1R may interact with Glu58 IGF-1. In comparison with IGF-1R, the equivalent arginine 717 IR was not associated with an important role in insulin binding in previous studies. This thesis is focused on clarifying the role of Arg704 IGF-1R and for comparison analogically on Arg717 IR isoform A (IR-A) in ligand binding to the receptors. Therefore, mutant variants of IGF-1R in positions His697 and Arg704 and variants IR-A in positions His710 and Arg717 were created. The role of histidines 697 IGF-1R and 710 IR was already elucidated...
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Type 1 diabetes mellitus in children and its impact on quality of life
KUČEROVÁ, Ludmila
This bachelor's thesis focuses on children suffering from type 1 diabetes mellitus and their parents. The aim of the bachelor's thesis was to assess how the parents of type 1 diabetic children evaluate the quality of life in connection with their children's disease and how the type 1 diabetics themselves evaluate it. A combination of qualitative and quantitative research strategies was chosen in the research. The structured interview technique was used in the qualitative strategy, and the PedsQLTM questionnaire was used in the quantitative part. Interviews were conducted with parents of children with type 1 diabetes and with the diabetics themselves. The interviews were recorded on a voice recorder and subsequently transcribed into a textual format in an electronic version. The questionnaire was used in both the version for children suffering from diabetes mellitus and in the version for parents of diabetics. The interviews were evaluated using open coding. Codes were then assigned to individual statements. The questionnaire was evaluated using descriptive statistics. The bachelor's thesis serves to increase public awareness of type 1 diabetes mellitus and its impact on the family.
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health benefits of the intermittent fasting
BRABCOVÁ, Simona
This bachelor thesis focuses on the issue of intermittent fasting and its impact on human health. The thesis is conceived as literary research. It presents various forms of intermittent fasting and their influence on physiological processes in the body and on specific diseases. Furthermore, this bachelor thesis focuses on negative side effects. The main aim of the thesis is to present the findings in a comprehensive form. The content of the thesis emerges mainly from foreign literature, articles and studies dealing with the issue. The work presents intermittent fasting as an alternative approach to eating with the potential to cure various diseases. It also discusses the advantages and disadvantages of other eating styles, such as a caloric restriction diet.
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The role of the teacher´s assistant in child with diabetes mellitus at the first grade of primary school.
SILOVSKÁ, Lucie
The goal of this bachelor´s work is to describe position of the assistent of the pedagogue at the student with diagnosis diabetes mellitus and suggest reducement of negative impacts of special educative needs of the student to the ecucation with a help of assistant of the pedagogue. Bachelor´s work consists of two parts. Teoretical part relyes on special literature. First part specialises in diabetes mellitus, its history, type of diabetes, its acute and chronic complications, aids for treatment of diabetes mellitus 1st type, treatment by insuline pump, nourishment and sport, last two chaptures are interested in student with diabetes at the elementary school. Second part of teoretical part is dedicated to the assistent of pedagogue, his/her aktivity and personal assumptions. Practical part is refering to own qualitative research, when research group was made up from students of chosen elementary schools. Students were chosen from 3 different elementary schools in Prague. Practical part consists of 3 case studies refering to the students at 1st level elementary school with diagnosis of diabetes mellitus. The data collection took place with a help of document study, interviews with parents, teachers and asistents of pedagogues and will be completed by observing. Preparation of this work came out from professional literature and publications, from laws and results of performer research.
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