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Mechanisms of insulin resistance in humans with focus on adipose tissue
Švehlíková, Eva ; Pelikánová, Terezie (advisor) ; Vondra, Karel (referee) ; Prázný, Martin (referee)
Endocrine activity of adipose tissue is implicated in the development of insulin resistance (IR). The thesis aimed to extend the knowledge of mechanisms contributing to IR. Study I - To investigate the effect of acute hyperinsulinaemia and acute angiotensin II type 1 receptor blockade (ARB) on plasma concentrations and subcutaneous adipose tissue (SAT) expressions of selected adipokines in patients with type 2 diabetes and healthy controls Study II - To investigate the effect of 3-week telmisartan treatment on insulin resistance and plasma concentrations and SAT expressions of selected adipokines in subjects with metabolic syndrome and impaired fasting glucose (IFG) Study III - To investigate the effect of prolonged hypertriglyceridaemia on plasma concentrations and SAT expressions of selected adipokines in patients with type 2 diabetes and healthy control subjects Study IV - To assess the plasma concentrations and SAT expressions of selected adipokines in subjects with different categories of glucose intolerance Methodology: Hyperinsulinaemic-euglycaemic clamp, Intralipid infusion and saline infusion were used to simulate specific metabolic conditions in vivo in 4 groups: 8 young healthy men, 11 overweight/obese patients with type 2 diabetes, 12 age-matched healthy controls and 12 overweight/obese patients...
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Clinical and genetic characteristic of selected types of monogenic diabetes mellitus
Gonsorčíková, Lucie ; Lebl, Jan (advisor) ; Pelikánová, Terezie (referee) ; Kohoutová, Milada (referee)
1. English Summary The aim of this thesis was to find out the etiology of diabetes mellitus in patients with a family predisposition to the disease. The world-wide increase in the incidence of diabetes in the past years has lead to intensive research of its etiological and pathophysiological mechanisms. This research has helped to discover many genes whose mutations were proved to cause diabetes without a contribution of other factors. Such cases where a mutation in a single gene crucial for glucose control is sufficient to result in diabetes are referred to as monogenic diabetes. This group includes a broad spectrum of hyperglycaemic conditions that differ significantly in their prevalence, course, treatment as well as prognosis. The so called MODY (maturity onset diabetes of the young) belongs to this group and is characterized by early onset before 25 years of age and no need of insulin substitution initially. In this study we were looking for mutations in genes that may be a rare cause of monogenic diabetes. We examined patients with hyperglycaemia occurring in several generations of their families and in whom mutations in more prevalent MODY genes had been previously excluded. We performed a genetic analysis of genes NEUROD1, IPF-1 and ABCC8. The protein NEUROD1 is a crucial transcription factor that...
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The effect of gluten-free diet on β-cell residual capacity, immune function and gut microbiome in children with newly diagnosed type 1. diabetes
Neuman, Vít ; Šumník, Zdeněk (advisor) ; Pelikánová, Terezie (referee) ; Škvor, Jaroslav (referee)
The effect of gluten-free diet on β-cell residual capacity, immune function and gut microbiome in children with newly diagnosed type 1. diabetes Abstract The pathophysiology of the onset and progression of type 1 diabetes (T1D) is not fully understood. Gluten has a proinflammatory effect on the immune system and is therefore considered as one of the factors affecting the onset and progression of T1D. The aim of the thesis is to allow a complex insight into the role of the GFD on the residual β-cell capacity, T1D control, gut microbiome, gut permeability, subtypes of immune cells and the effect of gut microbiome transfer into germ-free non-obese diabetic (NOD) mice on the incidence of diabetes. On the group of 45 children with T1D (26 intervention group, 19 control group) we proved the association of the GFD with slower decrease of β-cell residual capacity (the difference in the trend of C-peptide decrease 409 pmol/l/year; p = 0,04) and lower HbA1c (by 7,8 mmol/mol; p=0,02). We also described the changes in the gut bacteria that were differentially abundant after the administration of the GFD and the changes in abundance of the regulatory and effector immune cells. We showed there was no change in the gut permeability with respect to the study group. We also proved that the transfer of human gut microbiota...
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Quantification of insulin secretion after administration of whey proteins in healthy subjects and in patients with type 2 diabetes
Wildová, Elena ; Anděl, Michal (advisor) ; Pelikánová, Terezie (referee) ; Škrha, Jan (referee)
INTRODUCTION: Milk and milk proteins have higher insulinogenic index than glycemic index. This feature is mainly attributed to whey proteins. The main goal of this thesis was to evaluate a C-peptide response after administration of whey proteins in healthy individuals (study 1) and in patients with type 2 diabetes mellitus (study 2) in comparison to other experimental stimulation tests. METHODS: Eight young, healthy (7 males, 1 female; aged 20-26 years), non-obese (BMI: 17 - 25.9 kg/mš) participants with normal glucose tolerance were enrolled for study 1. Each individual underwent six C-peptide secretion tests in total. Three secretion tests measured C-peptide response to orally administered substances: whey proteins only (OWT), whey proteins with glucose (OWGT) and glucose only (OGTT, reference); while the other three secretion tests measured C-peptide response to intravenously administered substances: arginine (AST), glucagon (GST) and glucose (IVGTT, reference). Sixteen overweight (BMI 26,4 - 29,8 kg/m2) patients with type 2 diabetes mellitus, good glycemic control and with preserved fasting serum C-peptide levels (0,94 ± 0, 07 nmol/l) were enrolled for study 2. Two oral stimulation tests - one with 75 g of glucose (OGTT) and the other with 75 g of whey proteins (OWIST) - were used for assessing...
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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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Quantification of insulin secretion after administration of whey proteins in healthy subjects and in patients with type 2 diabetes
Wildová, Elena ; Anděl, Michal (advisor) ; Pelikánová, Terezie (referee) ; Škrha, Jan (referee)
INTRODUCTION: Milk and milk proteins have higher insulinogenic index than glycemic index. This feature is mainly attributed to whey proteins. The main goal of this thesis was to evaluate a C-peptide response after administration of whey proteins in healthy individuals (study 1) and in patients with type 2 diabetes mellitus (study 2) in comparison to other experimental stimulation tests. METHODS: Eight young, healthy (7 males, 1 female; aged 20-26 years), non-obese (BMI: 17 - 25.9 kg/mš) participants with normal glucose tolerance were enrolled for study 1. Each individual underwent six C-peptide secretion tests in total. Three secretion tests measured C-peptide response to orally administered substances: whey proteins only (OWT), whey proteins with glucose (OWGT) and glucose only (OGTT, reference); while the other three secretion tests measured C-peptide response to intravenously administered substances: arginine (AST), glucagon (GST) and glucose (IVGTT, reference). Sixteen overweight (BMI 26,4 - 29,8 kg/m2) patients with type 2 diabetes mellitus, good glycemic control and with preserved fasting serum C-peptide levels (0,94 ± 0, 07 nmol/l) were enrolled for study 2. Two oral stimulation tests - one with 75 g of glucose (OGTT) and the other with 75 g of whey proteins (OWIST) - were used for assessing...
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Energy metabolism control, selected genetic and hormonal factor
Vejražková, Daniela ; Bendlová, Běla (advisor) ; Rossmeisl, Martin (referee) ; Pelikánová, Terezie (referee)
I I I I I I I 4, CONCLUSIONS r) The postulatedaim of thework was fulfilled: Quite a large cohorts of DM2 patients,direct offspring of DM2 patients,and obese subjectsas well as a group of women suffering from PCOS, and sufficiently large groupof controlsubjectswerecompleted a. All the probands underwenta detailed anthropometricand biochemical characeterization b. The DNA bank was establishedandcompleted An electronicdatabasewas established Molecular geneticmethodsPCR, RFLP, andSSCP wereestablishedandoptimized Specific polymorphismsin the selectedcandidategenes were genotypedand unique data regarding genotypic frequenciesof these polymorphisms in Czech population wereobtained Genetic, biochemical and anthropometric data underwent statistical analysis. Especially associationsbetweengeneticpolymorphisms/adipocytokineconcentrations andanthropometric/biochemicalparametersweretested Final resultswere evaluatedand possibleeffectof the studiedgeneticpolymorphisms and/oradipocytokineson body compositionanďor biochemical statuswas assessed. Also an eventual involvement of the studied genetic and hormonal factors in aethiopathogenesisof obesity,DMZ, metabolicsyndrome,and PCOS was considered Main resultsand conclusionsof theresearchwerepublishedin scientificjournals.The publicationsrepresentthepivotal partof...
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The use of magnetic resonance spectroscopy for studying glucose metabolism
Kratochvílová, Simona ; Pelikánová, Terezie (advisor) ; Štich, Vladimír (referee) ; Polák, Jan (referee)
Magnetic resonance spectroscopy (MRS) is a noninvasive technique that enables to follow metabolic processes in selected tissues in vivo. Recently the attention has been focused on metabolic mapping in target organs of insulin action to describe the pathophysiology of insulin resistance. The aim of our study was to present the practical application of ³¹P (phosphorus) MRS and ¹H (proton) MRS in metabolic studies of skeletal muscle in insulin resistant subjects and in subjects with impaired fasting glucose. The third study was aimed to evaluate the brain metabolism with ¹H MRS in healthy controls and subjects with type 1 diabetes during hyperinsulinemia. ¹H and ³¹P MRS were performed using a MR Scanner Siemens Vision operating at 1,5 Tesla. To assess the parameters of glucose metabolism and insulin action oral glucose tolerance test and hyperinsulinemic euglycemic clamp were performed. The study 1 was aimed to evaluate the skeletal muscle (m. soleus) energetic metabolism in the offspring of hypertensive parents (OH) with a higher level of insulin resistance. The concentrations of selected high energy phosphates (phosphocreatine, inorganic phosphate, adenosintriphosphate, phosphomonoesters, phosphodiesters) were evaluated with ³¹P MRS. Their amount in OH was comparable to healthy controls. However we...
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Insulin resistance and postprandial state in type 2 diabetes. The effect of meal frequency and composition on glucose metabolism and other manifestations of the metabolic syndrome
Thieme, Lenka ; Pelikánová, Terezie (advisor) ; Kunešová, Marie (referee) ; Šmahelová, Alena (referee)
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...
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