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The importance of endocrinefunction of adipose tissue in the development of insulin resistance syndrome
Kaválková, Petra ; Haluzík, Martin (advisor) ; Karásek, David (referee) ; Kuneš, Jaroslav (referee)
(AJ) Adipose tissue produces numerous adipokines, pro- and antiinflammatory cytokines and hormones which may influence the development of insulin resistance, type 2 diabetes mellitus and other comorbidities of the metabolic syndrome. The ability of adipose tissue to store lipids and thus protect other organs and tissues from ectopic lipid accumulation and development of insulin resistance (IR) is largely dependent on the adipogenic potential of preadipocytes. The amount and function of these cells may be the key factor in creating "healthy" adipose tissue or on the contrary "unhealthy" adipose tissue eventually leading to metabolic derangements. The regulation of the amount of body fat by converting preadipocytes into mature adipocytes may be crucial in the prevention and treatment of obesity and its comorbidities. One of the reasons for development of insulin resistance can be the inhibition of the differentiation process of preadipocytes into mature adipocytes with consequent ectopic lipid accumulation caused by the secretion of preadipocyte factor - 1 (Pref - 1). Pref - 1 has been discovered recently as a protein produced by preadipocytes but not by mature adipocytes. Pref - 1 is a member of the protein family sharing similarity with epidermal growth factors which regulate the differentiation of...
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The role of incretin hormones in the development of type 2 diabetes mellitus
Marchal, Anna ; Haluzík, Martin (advisor) ; Brabcová, Iveta (referee)
Incretins are gut hormones secreted by cells located in the small intestine in response to ingestion of nutrients. The aim of this thesis is to describe their effect on the control of glucose homeostasis. Incretin receptors are widely distributed in multiple tissues and organs suggesting their complex effects including the regulation of glucose homeostasis and food intake by various mechanisms including both peripheral and central effects. Owing to their ability to regulate insulin secretion and glucose metabolism incretins have a potential in the treatment of type 2 diabetes mellitus. Incretin-based therapy strategies are discussed and compared in this thesis. Analogues of glucagon-like peptide-1, one of the incretin hormones, have the ability to lower body weight and therefore are considered as a possible obesity treatment both in patients with and without diabetes. The role of incretins in pathophysiology of obesity and studies carried out in order to evaluate its potential in the treatment of this disease are depicted. The thesis also involves an overview of possible role of incretins in metabolic effects of bariatric surgery. Keywords: Incretin hormones, GIP, GLP-1, type 2 diabetes mellitus, obesity.
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Endocrine role of adipose tissue in the pathogenesis of chronic inflammation in obesity and type 2 diabetes mellitus
Kratochvílová, Helena ; Haluzík, Martin (advisor) ; Taxová Braunerová, Radka (referee)
Adipose tissue as an active endocrine organ is explored in a number of processes associated with metabolic disorders. This work is aimed on studying the effect of endoscopically implantable weight-reducing device - duodeno-jejunal bypass liner - on subclinical inflammation of adipose tissue in obese patients, which contributes to the development of type 2 diabetes mellitus. Specifically, for patients implanted with duodeno- jejunal bypass liner we determined anthropometric, biochemical and hormonal characteristics, and mRNA expression of subcutaneous adipose tissue proinflammatory (TNF-α, leptin, CCL- 2, CX3CL1, CD40, CD80, CD86, CD206, CD163 and IL-6) and anti-inflammatory genes (Adiponektin, IL-10) before, one month and ten months after the intervention. The implantation of duodeno-jejunal bypass liner significantly decreased body weight, waist circumference, and improved metabolic and glycemic control. In addition, C-reactive protein a highly sensitive indicator of inflammatory processes in the body was reduced ten months after implantation. In the case of mRNA expression of CD86 (a marker of activated B lymphocytes and macrophages) there was temporarily increase in adipose tissue one month after the surgery and the subsequent significant decrease after ten months. mRNA expression of other...
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Diabetes mellitus and impairment of intestinal barier function
Hoffmanová, Iva ; Anděl, Michal (advisor) ; Haluzík, Martin (referee) ; Keil, Radan (referee)
Introduction: Impairment of intestinal barrier function is involved in pathogenesis of immune mediated diseases (such as type 1 diabetes mellitus or celiac disease) and metabolic diseases (such as type 2 diabetes mellitus). Aims of study: The first aim was to analyze impairment of mucosal part of intestinal barrier in both type of diabetes and to describe differences when compared to celiac disease, which is a typical condition associated with impairment of intestinal barrier function. The second aim was to find a correlation between duration or compensation of diabetes and intestinal barrier desintegration in patients with both type of diabetes, and to find a correlation between body mass index and intestinal barrier desintegration in patients with type 2 diabetes. The third aim was to assess influence of gluten-free diet on improvement of small intestinal mucosal integrity in patient with celiac disease. Methods: The study was performed on 166 individuals including healthy controls and five group of patients with: type 1 diabetes mellitus with fading insulitis (T1D), type 1 diabetes mellitus with ongoing insulitus (T1D/INS), type 2 diabetes mellitus (T2D), untreated celiac disease (CLD), and celiac disease on gluten-free diet (CLD-GFD). We tested the marker of epithelial apoptosis - cytokeratin 18...
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Factors affecting glucose metabolism and inflammatory response in critically ill patients
Kotulák, Tomáš ; Haluzík, Martin (advisor) ; Maruna, Pavel (referee) ; Šenolt, Ladislav (referee)
Hyperglycemia in critically ill patients was considered for many years an adaptive response to stress conditions being present in both patients with and without previous history of diabetes. Hyperglycemia is caused mainly by peripheral insulin resistance induced by the factors acting counteracting insulin signalling at the postreceptor level. Furthermore, hyperglycemia itself can then increase serum levels of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6 (Il-6) and interleukin-8 (Il- 8) and others. On the contrary, peripheral insulin resistance induced by pro- inflammatory cytokines may further potentiate hyperglycemia. White adipose tissue represents in addition to its energy storage function also a very active endocrine active organ. In addition to regulation of a number of metabolic processes it also significantly modulates the inflammatory response. In critically ill patients, adipose tissue changes its morphology, i.e. the adipocytes are shrinking and adipose tissue is abundantly infiltrated by macrophages. Paradoxically, overweight and obese critically ill patients have lower mortality than underweight, lean and morbidly obese subjects. In our studies, we selected population of the patients undergoing elective major cardiac surgery with extracorporeal...
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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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Antiproliferative effects of heme catabolic pathway's products
Koníčková, Renata ; Vítek, Libor (advisor) ; Haluzík, Martin (referee) ; Farghali, Hassan (referee)
Presented work is focused on heme metabolism with the main interest in bile pigments. Recent data indicate that bilirubin is not only a waste product of the heme catabolic pathway, but also emphasize its important biological impacts, including possible antiproliferative effects. Until today metabolism of bilirubin has not been completely elucidated, which has prevented detailed evaluation of its potential anticancer action. The aim of this study was to clarify some aspects of heme catabolism with respect for antiproliferative properties of its products. Based on the fact that bilirubin potently affects carcinogenesis of the intestine, we initially investigated not properly known bilirubin metabolism by intestinal bacteria. We studied bilirubin neurotoxic effects in hyperbilirubinemic Gunn rats - its distribution in the brain tissue and its degradation during pathological conditions, such as severe newborn jaundice or Crigler-Najjar syndrome. Possible approaches to improve the treatment of severe unconjugated hyperbilirubinemias, combination of the phototherapy and human albumin administration were also investigated. The main reason of these studies was the fact that mechanisms of neurotoxic effects of bilirubin are predominantly identical with those, by which bilirubin inhibits cancer cells growth....
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The role of adipose tissue in the pathophysiology of obesity and anorexia nervosa
Kratochvílová, Helena ; Haluzík, Martin (advisor) ; Pavlišová, Jana (referee)
The view of adipose tissue and its significance in human pathophysiology has changed substantially in the recent couple of years. It has been shown that adipose tissue is not only a passive storage site for excess energy, but that it actively participates in the maintenance of whole-body homeostasis as an endocrine organ producing various hormones and other biologically active molecules, which by acting in an endocrine, paracrine as well as autocrine fashion affect different organs and systems. An intact regulation of adipose tissue processes plays an important role in sustaining the integrity of the organism, whereas its defects lead to the development of a number of diseases. This thesis focuses primarily on the significance of adipose tissue in the pathogenesis of obesity and anorexia nervosa. In the last years, the incidence of obesity rapidly increases ranking, along with its complications, among the world's leading health problems. Obesity is associated with endocrine dysfunction of adipose tissue characterized by disrupted production of adipose tissue hormones and cytokines resulting in the development of numerous disorders including type 2 diabetes mellitus and cardiovascular diseases. A completely opposite disorder, where, however, adipose tissue, or more precisely the absence of it, plays...
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Mechanisms of insulin resistance and β - cell failure in type 2 diabetes. Effective diet against o minous octet
Kahleová, Hana ; Pelikánová, Terezie (advisor) ; Haluzík, Martin (referee) ; Vondra, Karel (referee)
Background and Aims: Dietary intervention is one of the key components in type 2 diabetes (T2D) management. Vegetarian diet is a promising alternative in the nutritional treatment of T2D. The aims of our study were: 1. To compare the effects of vegetarian and conventional diabetic diet with the same caloric restriction on insulin resistance, volume of visceral fat and plasma concentrations of oxidative stress markers after a 12-weeks-diet-intervention and subsequent 12-weeks of diet plus aerobic exercise training in subjects with T2D. 2. To explore the effect of 12 weeks of diet intervention and subsequent 12 weeks of diet combined with aerobic exercise training on -cell function and to evaluate the role of gastrointestinal peptides in subjects with T2D. 3. To study quality of life, Beck depression score and changes in eating behaviour in response to a vegetarian and a conventional diabetic diet. 4. To explore the role of changes in fatty acid composition of serum phospholipids in diet-induced changes in insulin sensitivity in subjects with T2D. 5. To follow-up our patients 1 year from the end of the intervention.
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The influence of central serotoninergic and dopaminergic activity on nutritional and metabolic parameters
Brunerová, Ludmila ; Anděl, Michal (advisor) ; Haluzík, Martin (referee) ; Yamamotová, Anna (referee)
THE INFLUENCE OF CENTRAL SEROTONINERGIC AND DOPAMINERGIC ACTIVITY ON NUTRITIONAL AND METABOLIC PARAMETERS MUDr. Ludmila Brunerová SUMMARY Introduction: Neuromediators dopamine and serotonin play a significant role in homeostatic and hedonic regulation of food intake, may exert direct metabolic effects and particularly serotonin influences affectivity. Their central activity could be quantified by functional tests. Common regulatory mediators of metabolism and affectivity represent an interesting research goal. Aims of study: The first aim was to describe the relationship between central serotoninergic activity measured by citalopram challenge test, affectivity, preference of macronutrients in food and metabolic profile in healthy men. The second aim was to confirm the use of sublingual apomorphine test as a functional test for assessment of central dopaminergic activity. The third aim was to reveal the relationship between central dopaminergic activity measured by sublingual apomorphine test, preference of macronutrients and metabolic profile. Methods: The study was performed on 42 healthy men (average age 43.5 ± 7.4 years and average BMI 27.4 ± 5.7 kg/mš) within 4 days with a week interval in between them. Anthropometric and...
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