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Signalling of protein kinase B and expression of cyclooxygenase in early phases of diabetic nephropathy
Ždychová, Jana ; Komers, Radko (advisor) ; Haluzík, Martin (referee) ; Matoušovic, Karel (referee) ; Škrha, Jan (referee)
Introduction: Renal hypertrophy, extracellular matrix accumulation, aItered apoptosis as well as changes in regional hemodynamics have been implicated in the pathophysiology of nephropathy in diabetes mellitus (DM). On the molecular level the detailed mechanisms for development of diabetic nephropathy (DN) have becn intensively studied. Insulin induces a variety of biologicaI effects in a number of cell types via phosphatidylinositol-3 kinase (PI3K)/Akt kinase signaling pathway. Considering multiple function of Akt that incIude potentiaIly hannful pro-growth effects mediated by mTOR and cyclooxygenas-2 (COX-2), as well as protective effects mediated by endotheliaI nitric oxide synthase (eNOS), it is possible that aIterations in activities of Akt may play role in the pathophysiology ofDN. Renal corticaI activity and expression of Akt, its down-strearn effectors mTOR, eNOS, and "C<JIX-:Z. as well as PTEN, an endogenous Akt inhibitor, were investigated in streptozotocin (STZ): diabetic rats as a model of Type 1 DM with different levels of glycenůc control, and in Zucker ~d.iabetic fatty rats, a model ofDM2, and in nondiabetic rats as controls. Methods: Akt activity was measured by kinase assay. Protein expressions were measured by .immunoblotting and immunohistochemistry in renal cortex of 4- and 12- week old...
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Gene polymorphisms of antioxidant enzymes and diabetes mellitus
Flekač, Milan ; Škrha, Jan (advisor) ; Bendlová, Běla (referee) ; Rybka, Jaroslav (referee)
Paraoxonase 1 (PON1), an antioxidant enzyme closely associated with HDL(high-density lipoproteins), preserves LDL (low density lipoproteins) against oxidation. Less protection may be therefore supposed by decreased PON1 activity.This study was undertaken to investigate the association of PON1 gene polymorphisms with diabetic angiopathy and to evaluate the relationship of these polymorphisms with PON1 activity. Total of 86 Type 1 (T1DM) and 246 Type 2 (T2DM) diabetic patients together with 110 healthy subjects were examined. DNA isolated from leukocytes was amplified with polymerase chain reaction (PCR) followed by restriction enzyme digestion. The products were analyzed for L55M and Q192R polymorphisms in coding region and for -107 C/T and -907 G/C in promotor sequence of PON1. Serum enzyme activity was measured spectrophotometrically. Significant differences were found between T1DM or T2DM and control persons in L55M polymorphism (allele M more frequent in T1DM and T2DM vs. controls, p<0,05) and Q192R polymorphism (R allele less frequent in T1DM and T2DM vs. controls, p<0,01) of the PON1 gene. Serum PON1 activity was significantly decreased in T1DM (110±68 nmol/ml/min) and T2DM patients (118±69 nmol/ml/min) compared to the control persons (203±58 nmol/ml/min), both p<0,01. The presence of MM and QQ...
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název v anglickém jazyce není uveden
Kasalová, Zdislava ; Škrha, Jan (advisor) ; Piťha, Jan (referee) ; Kittnar, Otomar (referee)
Diabetes mellitus, hypercholesterolaemia and arterial hypertension are the best known risk factors of atherosclerosis- the most common macrovascular disease. The aim of our work was to asses influence of this risk factors on microcirculation. We supposed, that the smallest vessels are the most sensitive to the noxious influence and that microvascular disorder will be early indicator of vascular impairment. Our work has shown, that risk factors influence on microcirculation is completely different, in the contrast with relatively uniform influence on macrovaslular level. Diabetes mellitus presents two completely different entities, from the microvascular point of view. Pathogenesis of microvascular and macrovascular complications in Type 1 and Type 2 diabetes mellitus is the same- it is the long- term hyperglycaemia, but it's influence on microvascular reactivity is completelly different. In Type 1 diabetic patients, microvascular reactivity impairment develops later, and it is in correlation with presence and severity of the most common microvascular complication- peripheral neuropathy. On the contrary, in Type 2 diabetes mellitus microvascular reactivity impairment occures in early stage of this dissease and is not connected with presence and severity of peripheral neuropathy. In patients with...
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