Autor seznamuje se současnými názory na etiopatogenezu diabetes mellitus 2. typu (DM2T). Ukazuje toto onemocnění jako nemoc chronickou a progredující, a proto vyžadující dynamický přístup k léčbě. Na těchto základech potom předkládá současné armamentárium perorálních antidiabetik i možnosti jejich kombinace. Vedle stávajících léčebných možností ukazuje také další, v bezprostřední budoucnosti využitelné novinky v této lékové skupině., Jindřich Olšovský, and Lit. 7
The concentration-dependence of tert-butyl hydroperoxide (BHP) inhibitory effect on oxygen consumption in isolated rat liver mitochondria was measured in the presence of various respiratory substrates. Strong inhibitory effect at low concentrations of BHP (15-30 μM) was found for oxoglutarate and palmitoyl carnitine oxidation. Pyruvate and glutamate oxidation was inhibited at higher concentrations of BHP (100-200 μM). Succinate oxidation was not affected even at 3.3 mM BHP. Determination of mitochondrial membrane potential has shown that in the presence of NADH-dependent substrates the membrane potential was dissipated by BHP but was completely restored after addition of succinate. Our data thus indicate that beside peroxidative damage of complex I also various mitochondrial NADH-dependent dehydrogenases are inhibited, but to a different extent and with different kinetics. Our data also show that succinate could be an important nutritional substrate protecting hepatocytes during peroxidative damage., R. Endlicher ... [et al.]., and Obsahuje seznam literatury
Diabetes mellitus is relatively frequently associated with fatty liver disease. Increased oxidative stress probably plays an important role in the development of this hepatopathy. One of possible sources of reactive oxygen species in liver is peroxisomal system. There are several reports about changes of peroxisomal enzymes in experimental diabetes, mainly enzymes of fatty acid oxidation. The aim of our study was to investigate the possible changes of activities of liver peroxisomal enzymes, other than enzymes of beta-oxidation, in experimental diabetes mellitus type 2. Biochemical changes in liver of experimental animals suggest the presence of liver steatosis. The changes of serum parameters in experimental group are similar to changes in serum of patients with non-alcoholic fatty liver disease. We have shown that diabetes mellitus influenced peroxisomal enzymes by the different way. Despite of well-known induction of peroxisomal beta-oxidation, the activities of catalase, aminoacid oxidase and NADH-cytochrome b5 reductase were not significantly changed and the activities of glycolate oxidase and NADP-isocitrate dehydrogenase were significantly decreased. The effect of diabetes on liver peroxisomes is probably due to the increased supply of fatty acids to liver in diabetic state and also due to increased oxidative stress. The changes of metabolic activity of peroxisomal compartment may participate on the development of diabetic hepatopathy., L. Turecký, V. Kupčová, E. Uhlíková, V. Mojto., and Obsahuje bibliografii
In as early as 1997, the World Health Organization officially recognized obesity as a chronic disease. The current epidemic of obesity and overweightness has aroused great interest in the study of adipose tissue formation. The transcription factor peroxisome proliferator-activated receptor γ (PPARγ) binds to the target gene promoter regulatory sequences, acting as a key factor in regulating the differentiation of preadipocytes in the adipose tissue, and plays an important role in regulating the adipocyte metabolism. A further understanding of the structure and expression characteristics of PPARγ, in addition to its mechanisms of action in adipocyte differentiation, may be applied to control obesity and prevent obesity-related diseases. In this article, recent studies investigating the effect of regulating PPARγ on adipocyte differentiation are reviewed. In particular, the structural characteristics, expression patterns, and molecular mechanisms of PPARγ function in adipocyte differentiation are considered., Hui Wu, Xiaohua Li, Chunyan Shen., and Obsahuje bibliografii
Several studies have shown that peroxynitrite (ONOO– ), formed upon the reaction of •NO and O2–, is increased in many cardiovascular diseases and is detrimental to myocardial function. Proteins associated with Ca2+ homeostasis regulation in the heart may be involved in these effects. Thus, the aim of this study was to elucidate the mechanisms associated with ONOO– -induced effects. We evaluated [Ca2+]i regulation, sarco/endoplasmic reticulum Ca2+- binding proteins, and phosphorylation levels of the ryanodine receptor in isolated rat myocytes. Electrical field-induced intracellular Ca2+ transients and contractions were recorded simultaneously. Myocytes superfused with 3-morpholinosydnonimine N-ethylcarbamide (SIN-1), an ONOO– donor, decreased the amplitude of Ca2+ transients and contraction in a dose-response (1–200 µM) manner. Similarly, SIN-1 increased half-time decay in a concentration-dependent manner. Co-infusion of the ONOO– donor with FeTMPyP (1 µM), an ONOO– decomposition catalyst, inhibited the effects induced by ONOO– . Impaired sarcoplasmic reticulum Ca2+ uptake caused by ONOO– (SIN-1 200 µM) was confirmed by a reduction of caffeine-evoked Ca2+ release along with prolongation of the half-time decay. Surprisingly, ONOO– induced a spontaneous Ca2+ transient that started at the beginning of the relaxation phase and was inhibited by tetracaine. Also, reduced phosphorylation at the ryanodine receptor 2 (RyR2)-Ser-2814 site was observed. In conclusion, deficient sarco/endoplasmic reticulum Ca2+-ATPase-mediated Ca2+ uptake concomitant with augmented Ca2+ release by RyR2 in myocytes may be associated with modification of myocyte Ca2+ handling by ONOO– . Thus, development of cardiac failure in diabetes, nephropathy, or hypertension may be related with elevated ONOO–in cardiac tissue.