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The role of protein kinase C in the pathogenesis of insulin resistance and its complications
Marková, Irena
Charles University in Prague, Faculty of Science Department of Biochemistry The role of protein kinase C in the pathogenesis of insulin resistance and its complications Mgr. Irena Marková Ph.D. thesis Supervisor: Doc. RNDr. František Novák, CSc. Faculty of Science, Charles University in Prague Department of Biochemistry Consultant Supervisor: Ing. Ludmila Kazdová, CSc. Institute for Clinical and Experimental Medicine in Prague Department of Metabolism and Diabetes Prague 2010 2 INTRODUCTION Metabolic syndrome (MS) represents a cluster of metabolic disorders that increase the risk of type 2 diabetes (DM2) and cardiovascular diseases [1]. The relevancy of MS is shown by its high prevalence and also by the fact that it plays a key role in the pathogenesis of many disorders, especially DM2, obesity, hypertension, cardiovascular diseases and others [2]. MS is characterized by tissue resistance to insulin action, hyperinsulinemia, impaired glucose tolerance and dyslipidemia, essential hypertension, abdominal (visceral) obesity, hyperuricaemia, coagulation disturbances and fibrinolysis, and endothelial dysfunction [3]. Insulin resistance (IR) is a basic metabolic abnormality of MS. It is a common pathological state in which target cells fail to respond to ordinary levels of circulating insulin [4]. It results in...
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The role of protein kinase C in the pathogenesis of insulin resistance and its complications
Marková, Irena
Charles University in Prague, Faculty of Science Department of Biochemistry The role of protein kinase C in the pathogenesis of insulin resistance and its complications Mgr. Irena Marková Ph.D. thesis Supervisor: Doc. RNDr. František Novák, CSc. Faculty of Science, Charles University in Prague Department of Biochemistry Consultant Supervisor: Ing. Ludmila Kazdová, CSc. Institute for Clinical and Experimental Medicine in Prague Department of Metabolism and Diabetes Prague 2010 2 INTRODUCTION Metabolic syndrome (MS) represents a cluster of metabolic disorders that increase the risk of type 2 diabetes (DM2) and cardiovascular diseases [1]. The relevancy of MS is shown by its high prevalence and also by the fact that it plays a key role in the pathogenesis of many disorders, especially DM2, obesity, hypertension, cardiovascular diseases and others [2]. MS is characterized by tissue resistance to insulin action, hyperinsulinemia, impaired glucose tolerance and dyslipidemia, essential hypertension, abdominal (visceral) obesity, hyperuricaemia, coagulation disturbances and fibrinolysis, and endothelial dysfunction [3]. Insulin resistance (IR) is a basic metabolic abnormality of MS. It is a common pathological state in which target cells fail to respond to ordinary levels of circulating insulin [4]. It results in...
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The role of protein kinase C in the pathogenesis of insulin resistance and its complications
Marková, Irena ; Novák, František (advisor) ; Zeman, Miroslav (referee) ; Zídková, Jarmila (referee)
18 effects of TZDs are probably due to the remodeling of adipose tissue and increased adiponectin secretion. SUMMARY Studying the pathogenesis of insulin resistance and the role of PKC in insulin resistance In HHTg rats, elevated serum triglycerides and FFA were associated with the ectopic accumulation of triglycerides in tissues and reduced insulin sensitivity of peripheral tissues. Impaired glucose utilization in the peripheral tissues was associated with the reduced activity of GS in skeletal muscle. Decreased GS activity and glucose utilization in peripheral tissues indicate a possible defect in insulin signal transduction. In line with this, our results show that skeletal muscle IR was associated with the increased activation and translocation of PKC θ. Nutritionally induced obesity of HHTg rats resulted, in many cases, in the further deterioration of metabolic abnormalities associated with IR. We found that PKC θ, in particular, could contribute to the metabolic abnormalities associated with IR and obesity. The age-related increase in IR and deterioration of some parametres of carbohydrate and lipid metabolism, were not associated, in HHTg rats, with obesity but with increased serum levels of triglycerides and FFA. The age-related worsening of IR in HHTg rats was accompanied by increased...
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