Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are aging-associated diseases that have rising prevalence in all industrialized countries. AD is a neurodegenerative disease characterized by progressive loss of cognitive functions. It is a complex disease which formation involves both genetic factors and environmental factors. The most important marker associated with this disease is the risk allele ε4 in APOE gene. From the latest genome-wide association study emerged another ten candidate genes. As the most significant from those genes appears the minority G allele of rs744373 polymorphism in the gene BIN1. AD is connected with many metabolic and immune disorders. To the markers of interest belongs also the new parameter visfatin which can act as a pro-inflammatory cytokine. T2DM is a chronic disease characterized by raised levels of blood glucose, which is also characterized by neurological disorders. In the case of both of these diseases can be found a large number of metabolic disorders. One of the most important disorders is insulin resistance. This thesis consists of two parts - the biochemical and genetic one. The biochemical part of the thesis studies the visfatin level in patients with AD and healthly control and studies whether visfatin is related to AD. In this part of the...

(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...

(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...

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...

Submitted by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2018-10-15T15:07:19Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇÃO_Hillene Freitas_2017.pdf: 1239371 bytes, checksum: 28d8e6b643ebaa9c5e9617e87719de30 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2018-10-15T15:07:30Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇÃO_Hillene Freitas_2017.pdf: 1239371 bytes, checksum: 28d8e6b643ebaa9c5e9617e87719de30 (MD5) / Made available in DSpace on 2018-10-15T15:07:30Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇÃO_Hillene Freitas_2017.pdf: 1239371 bytes, checksum: 28d8e6b643ebaa9c5e9617e87719de30 (MD5) Previous issue date: 2017-05-11 / The object of the study was the dialogical process in the care relationship between health care agents and subjects with diabetes mellitus 2, in the primary health care, family health care strategy. The theoretical assumptions of health psychology, community orientation, and concepts about subjectivity, dialogue and mediation in health care were central to our analysis. The main objectives were: to investigate the mediation and dialogue processes of ACS with subjects/users with DM2, inserted in the Hiperdia Program, in a UBSF, in Manaus; To identify the health care practices of ACS in the assigned territory of a UBSF; to characterize the health care practices of the ACS in the Hiperdia Program in the context of this UBSF. The qualitative methodology of the Participating Observation in the field of research (UBSF), used the field diary and documentary material, respecting the ethical norms in research. The researcher was inserted as a participant observer in the daily life of the UBSF, interacting with the professionals of the multidisciplinary team and users of the unit, in a general way. And, more directly, with the community health care agents and users of the Hiperdia Program. In this unit, the five community health care agents were women. All agreed to participate in the research and signed the Informed Consent Term. The analysis of the corpus was performed in coherence with the theoretical assumptions of health psychology and the field methodology used. The results showed the precariousness and vulnerability of the population and dwellings of the affiliated territory of the UBSF, where the ACS work in daily life. The ACS practices are more focused on preventive care work, particularly, observing the behaviors and situations of risk of illness and aggravation of the same, acting as mediators between the users and multidisciplinary team. In the Hiperdia Program, the actions of mediation of the ACS, valued both the subjective aspects of the subjects / users and those of the glycemic control, of the practice of physical exercises in DM2. An example of the care pathways of an ACS in the territory was singled out, highlighting a care relationship in a dialogical process, with availability and solidarity regarding the subjects/users of DM2. In the final considerations, it is suggested the deepening of the research on the dialogic processes underlying the care relationships of the ACS in their daily practice. / O objeto do estudo foi o processo dialógico na relação de cuidados entre agentes de saúde e sujeitos com diabetes mellitus 2, na atenção básica, estratégia saúde da família. Os pressupostos teóricos da psicologia da saúde, de orientação comunitária, e os conceitos sobre subjetividade, diálogo e mediação nos cuidados à saúde foram fundamentais para a nossa análise. Os objetivos principais foram: investigar os processos de mediação e de diálogo das ACS com sujeitos/usuários com DM2, inseridos no Programa Hiperdia, em uma UBSF, em Manaus; identificar as práticas de cuidados à saúde das ACS no território adstrito de uma UBSF; caracterizar as práticas de cuidados à saúde das ACS no Programa Hiperdia no contexto dessa UBSF. A metodologia qualitativa da Observação Participante, no campo investigativo (UBSF), utilizou o diário de campo e material documental, respeitando as normas éticas em pesquisa. A pesquisadora esteve inserida como observadora participante no cotidiano da UBSF, interagindo com os profissionais da equipe multidisciplinar e usuários da unidade, de uma forma geral. E, mais diretamente, com as agentes comunitárias de saúde e usuários do Programa Hiperdia. Nesta unidade, as cinco agentes comunitárias de saúde eram mulheres. Todas concordaram em participar da pesquisa e assinaram o Termo de Consentimento Livre e Esclarecido. A análise do corpus foi realizada em coerência com os pressupostos teóricos da psicologia da saúde e da metodologia de campo utilizada. Os resultados mostraram a precariedade e vulnerabilidade da população e moradias do território adstrito da UBSF, onde as ACS atuam no cotidiano. As práticas das ACS são mais voltadas ao trabalho de cuidados preventivos, particularmente, observando os comportamentos e situações de risco de adoecimento e de agravamento do mesmo, atuando como mediadoras entre os usuários e equipe multidisciplinar. No Programa Hiperdia, as ações de mediação das ACS, valorizavam tanto os aspectos subjetivos dos sujeitos/usuários quanto aqueles do controle da glicemia, da prática de exercícios físicos em DM2. Foi individualizado um exemplo de percursos de mediação de cuidados de uma ACS no território, destacando-se uma relação de cuidados em processo dialógico, com disponibilidade e solidariedade em relação aos sujeitos/usuários de DM2. Nas considerações finais, sugere-se o aprofundamento da pesquisa sobre os processos dialógicos subjacentes às relações de cuidados das ACS em sua prática cotidiana.

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...

(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...

(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...

NOVEL METABOLIC REGULATORS AND PROINFLAMMATORY FACTORS IN THE ETIOPATHOGENESIS OF TYPE 2 DIABETES MELLITUS AND OBESITY: THE INFLUENCE OF PHARMACOLOGICAL AND DIETARY INTERVENTIONS MUDr. Miloš Mráz Doctoral Thesis ABSTRACT (EN) Identifying novel factors involved in the etiopathogenesis of obesity, diabetes mellitus and their complications has become one of the primary scopes of metabolic research in the last years. The aim of the present study was to evaluate the role of recently discovered metabolic and inflammatory regulators including fibroblast growth factors 19 and 21 and chemotactic cytokines in the development of obesity and type 2 diabetes mellitus (DM2). A total number of 182 patients were included into the study. They were divided into 3 groups - patients with obesity but without type 2 diabetes mellitus, individuals with obesity and type 2 diabetes mellitus and healthy control normal-weight subjects. Selected interventions included 2 to 3 weeks of very-low-calorie diet (VLCD - energy content 2500 kJ/day), 3 months of administration of PPARα receptor agonist fenofibrate and acute hyperinsulinemia during hyperinsulinemic isoglycemic clamp. Our results indicate that the increase of circulating FGF-21 levels after VLCD and fenofibrate treatment could contribute to positive metabolic effects of these...

This thesis focuses on the effects of n-3 polyunsaturated fatty acids (n-3 PUFA) on development of non-alcoholic fatty liver disease (NAFLD) in experiment, on prevalence of this condition in patients with type 2 diabetes mellitus and metabolic syndrome and also on non-invasive diagnostics. The aim was to study the effect of n-3 PUFA on NAFLD development in an experimental model and based on analysis of a group of patients with type 2 diabetes and metabolic syndrome to assess the prevalence of this condition. Lastly we aimed to evaluate non-invasive diagnostic methods of liver fibrosis and NASH. We demonstrated beneficial effects of n-3 PUFA administration on NAFLD development in a C57/Bl6 mice high fat methionin-cholin defficient dietary model of NAFLD. n-3 PUFA administration led to biochemical improvement, decrease of lipid accumulation in the liver as well as improvement of histology. These effects are determined by complex modulation of lipid metabolism, mainly due to decrease in availability of fatty acids for triglyceride synthesis in the liver, changes of adipokine levels and amelioration of proinflammatory status in the liver. In a group of type 2 diabetics we found NAFLD prevalence of almost 80%, 14% of these patients had also signs of liver fibrosis or cirrhosis. Non-invasive methods...