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Insulin secretion in women with polycystic ovary syndrome
Grimmichová, Tereza ; Haluzík, Martin (advisor) ; Marešová, Dana (referee) ; Rešlová, Taťána (referee)
Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies occuring in 5-10% women in their fertile years. The incidence of impaired glucose tolerance and diabetes mellitus type 2 is significantly increased in PCOS. Hyperinsulinaemia and insulin resistance are present in a relevant number of PCOS women. In our projects we therefore concentrated on various aspects of insulin secretion in PCOS women. We used different approaches and calculations, which are complementary to each other and provide a more detailed insight into possible beta cell dysfunction. Aims of our studies were 1) examine how the beta cell function is influenced by the family history of DM 2, 2) examine the insulin pulsatile secretion, 3) examine the secretion of incretins and 4) examine the prevalence of glucose intolerance and its potential prediction in PCOS women. 1) Decreased insulin sensitivity was observed only in PCOS women with the positive family history of DM 2 in comparison to healthy controls. If these women have normal glucose tolerance, they compensate the decreased insulin sensititivity by the increased insulin secretion. 2) Lean PCOS women had similar insulin pulsatile secretion patterns with the exception of broader insulin peaks in comparison to healthy controls. Insulin sensitivity was not associated...
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Local metabolism of glucocorticoids in female Prague hereditary hypertriglyceridemic rats
Klusoňová, Petra ; Pácha, Jiří (advisor) ; Kopecký, Jan (referee) ; Haluzík, Martin (referee)
11-hydroxysteroid dehydrogenase (11HSD1) is an oxidoreductase which catalyzes conversion of inactive 11-oxo steroid derivatives into active 11-hydroxy forms. 11HSD1 elevates intracellular level of active glucocorticoid (GC) hormones: cortisol in human tissues and corticosterone in rodents, therefore local level of active GCs can be set independently from systemic secretion driven by hypothalamo-pituitary-adrenal axis (HPA axis). Chronic systemic excess of GCs results in development of Cushing's syndrome which is characterised by central obesity and other metabolic disturbances. Despite normal serum levels of GCs, the patients with idiopathic obesity also develop metabolic syndrome. It was suggested that GCs could be elevated locally in target tissues due to enhanced 11HSD1 activity. This hypothesis was confirmed in transgenic rodent models. Prague hereditary hypertriglyceridemic (HHTg) rats represent a non-obese model of metabolic syndrome without genetic manipulations or specific mutations. The strain was bred by cross-mating of Wistar rat individuals with elevated serum levels of triglycerides (TGs). The strain exhibit hypertriglyceridemia and hypertension. When kept on high carbohydrate diet HHTg rats exhibit alterations in glucose homeostasis. Since there are no data that would describe...
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The role of adipose tissue in endothelial dysfunction, etherosclerosis and other complications of metabolic syndrome: influence of diet and pharmacotherapy
Doležalová, Radka ; Haluzík, Martin (advisor) ; Šenolt, Ladislav (referee) ; Kábrt, Jan (referee)
The metabolic effects of obesity have made this disease one of the most common risk factors for diabetes, hypertension, and atherosclerosis. Adipose tissue is now recognized as an active secretory and immune organ. Chronic inflammation is a common feature of the obesity, and inflammatory signals may originate within visceral adipose tissue as this fat depot expands in response to chronic positive energy balance. Both adipocytes and macrophages within fat secrete numerous hormones and cytokines that have local effects on WAT physiology but also systemic effects on other organs and may markedly contribute to the development of pathophysiological disorders associated with metabolic syndrome. On the contrary, leanness as well as significant weight reduction in obese patients increases production and circulating levels of metabolically beneficial factors and decreases production of proinflammatory and insulin resistance-inducing factors. Endothelial dysfunction and inflammation are important signs of vascular risk and worsened prognosis in patients with metabolic syndrome and type 2 diabetes. Measures of endothelial function remain invaluable for research into disease mechanism and response to new therapies. An interesting area of ongoing investigation is the role of thiazolidinediones in improving endothelial...
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Bipolar Disorder and Diabetes Mellitus
Růžičková, Martina ; Höschl, Cyril (advisor) ; Haluzík, Martin (referee) ; Papežová, Hana (referee)
Despite lots of research, the genetic and pathophysiological basis of bipolar disorder (BD) remains unclear. One of the possible reasons is that BD spectrum comprises a heterogeneous group of different subtypes of the illness sharing certain pathophysiological or genetic mechanisms. Patients with co-morbid diabetes mellitus (DM) may represent such a subgroup of BD with a distinct pathophysiology and possibly different clinical characteristics of BD. This thesis is aimed at investigating the possible link between BD and DM. Bipolar patients have about 3 times higher risk of DM (type 2 in particular). The first part of my thesis outlines the possible links between DM and BD, including medication, alterations in the hypothalamo-pituitary axis and signal transduction, and genetics. In the second part, I examined the possible differences in clinical characteristics between patients with (N=26) and without (N=196) co-morbid DM. Next, I examined the variables showing differences between groups, using logistic regression. Patients were recruited via The Maritime Bipolar Registry. The prevalence of DM was 11.7%. Diabetic patients were significantly older than non-diabetic patients (P < 0.001), had higher rates of rapid cycling (P = 0.02), more chronic course of BD (P = 0.006), more disability (P < 0.001), lower...
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Effects of acute starvation and of type 2 diabetes mellitus upon insulin resistance and substrate utilization in obese subjects
Duška, František ; Anděl, Michal (advisor) ; Haluzík, Martin (referee) ; Mourek, Jindřich (referee) ; Stárka, Luboslav (referee)
Very-low calorie diet or even total short-term fasting is widely used in clinical practice in order to improve metabolic compensation of patients with type 2 diabetes mellitus. Although benefits of weight reduction are well proven in T2DM, much less is known about effects of acute starvation, during which the interruption of the afflux of energy substrates is not followed by a major change of body composition. We hypothesize the improvement of insulin effects on glucose metabolism in T2DM as these patients may lack the key metabolic responses which impair insulin sensitivity in lean, non-diabetic subjects. Moreover, we assume according to "thrifty genotype hypothesis" that protein wasting during starvation will be positively related to insulin effects on glucose disposal and negatively related to insulin antilipolytic and antiketogenic effects. In the light of this we designed an observational, prospective, in-hospital study, comparing the effects of 60 hours fast on various aspects of insulin resistance, endocrine regulation and metabolism in 10 patients with T2DM and 10 obese controls without diabetes (OB).
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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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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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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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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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The role of GH/IGF-1 axis components in the etiopathogenesis of metabolic disturbances in type 2 diabetes mellitus and acromegaly
Toušková, Věra ; Haluzík, Martin (advisor) ; Müllerová, Dana (referee) ; Saudek, František (referee)
(EN) GH/IGF-1 axis components (GH, growth hormone receptor (GH-R), IGF-1, IGF-1 receptor (IGF-1R), IGF-binding proteins (IGFBPs)) participate in the control of glucose metabolism, inflammatory processes as well as cell proliferation and differentiation, including adipocytes and monocytes. The aim of the present study was to evaluate the role of local mRNA expression of GH/IGF-1 axis components in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) in the development of insulin resistance and differences of adipose tissue mass in following groups of patients: obese females with and without type 2 diabetes mellitus and subjects with active untreated acromegaly. A total number of 66 subjects were included in the study: obese females without type 2 diabetes mellitus (OB), obese females with type 2 diabetes mellitus (T2DM), acromegalic patients (AC) and healthy lean control subjects (C). T2DM underwent 2 weeks of very-low- calorie diet (VLCD - energy content 2500 kJ/day). According to our results we suggest that decreased mRNA expression of IGF-1, IGF-1R, IGFBP-2 and IGFBP-3 in adipose tissue of T2DM subjects may contribute to changes of fat differentiation capacity and the increased IGF-1R mRNA expression in peripheral monocytes in these patients may play a role in the regulation of...
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