Glucose-dependent insulinotropic peptide (GIP) contributes to incretin effect of insulin secretion which is impaired in Type 2 diabetes mellitus. The aim of this study was to introduce a simple meal test for evaluation of GIP secretion and action and to examine GIP changes in Type 2 diabetic patients. Seventeen Type 2 diabetic patients, 10 obese non-diabetic and 17 nonobese control persons have been examined before and after 30, 60 and 90 min stimulation by meal test. Serum concentrations of insulin, C-peptide and GIP were estimated during the test. Impaired GIP secretion was found in Type 2 diabetic patients as compared with obese non-diabetic and non-obese control persons. The AUCGIP during 90 min of the meal stimulation was significantly lower in diabetic patients than in other two groups (p<0.03). Insulin concentration at 30 min was lower in diabetic than in non-diabetic persons and the GIP action was delayed. The ΔIRI/ΔGIP ratio increased during the test in diabetic patients, whereas it progressively decreased in obese and nonobese control persons. Simple meal test could demonstrate impaired GIP secretion and delayed insulin secretion in Type 2 diabetic patients as compared to obese non-diabetic and nonobese healthy control individuals., J. Škrha., and Obsahuje bibliografii a bibliografické odkazy
b1_Rats with diabetes induced by streptozotocin (STZ) and nicotinamide (NA) are often used in animal studies concerning various aspects of diabetes. In this experimental model, the severity of diabetes is different depending on doses of STZ and NA. Moreover, diabetic changes in rats with STZ-NA-induced diabetes are not fully characte rized. In our present study, metabolic changes and insulin secretion were investigated in rats with diabetes induced by administration of 60 mg of STZ and 90 mg of NA per kg body weight. Four to six weeks after diabetes induction, insulin, glucagon and some metabolic parameters were determined to evaluate the severity of diabetes. Moreover, insulin secretory capacity of pancreatic islets isolated from control and diabetic rats was compared. It was demonstrated that admi nistration of 60 mg of STZ and 90 mg of NA per kg body weight induced relatively mild diabetes, since insulin, glucagon an d other analyzed parameters were only slightly affected in diabetic rats compared with control animals. In vitro studies revealed that insulin secretory response was preserved in pancreatic islets of diabetic rats, however, was lower than in islets of control animals. This effect was observed in the presence of different stimuli. Insulin secretion induced by 6.7 and 16.7 mmol/l glucose was moderately reduced in islets of diabetic rats compared with control islets. In the presence of leucine with glutamine, insulin secretion appeared to be also decreased in islets of rats with STZ-NA-induced diabetes. Insulinotropic action of 6.7 mmol/l glucose with forskolin was also deteriorated in diabetic islets. Moreover, it was demonstrated that at a non-stimulatory glucose, pharmacological depolarization of plasma membrane with a concomit ant activation of protein kinase C evoked significant rise in insulin release in islets of control and diabetic rats., b2_However, in diabetic islets, this effect was attenuated. These results indicate that impairment in insulin secretion in pancreatic islets of rats with mild diabetes induced by STZ and NA result s from both metabolic and nonmetabolic disturbances in these islets., T. Szkudelski, A. Zywert, K. Szkudelska., and Obsahuje bibliografii a bibliografické odkazy
The microcirculation, like all physiological systems undergoes modifications during the course of pregnancy. These changes aid the adaption to the new anatomical and physiological environment of pregnancy and ensure adequate oxygen supply to the fetus. Even though the microcirculation is believed to be involved in major pregnancy related pathologies, it remains poorly understood. The availability of safe and non-interventional technologies enabling scientists to study the intact microcirculation of the pregnant patient will hopefully expand our understanding. In this article we review the physiological changes occurring in the microcirculation during pregnancy and the role of the microcirculation in gestational related pathologies. We will also describe the available techniques for the measurement and evaluation of the microcirculation. Lastly we will highlight the possible fields in which these techniques could be utilized to help provide a clearer view of the microcirculation in the pregnant woman., I. Abdo, R. B. George, M. Farrag, V. Cerny, C. Lehmann., and Obsahuje bibliografii
Previous data suggest that type 1 diabetes mellitus leads to the deterioration of myocardial intercellular communication mediated by connexin-43 (Cx43) channels. We therefore aimed to explore Cx43, PKC signaling and ultrastructure in non -treated and omega-3 fatty acid (omega-3) treated spontaneously diabetic Goto-Kakizaki (GK) rats considered as type 2 diabetes model. Four-week-old GK and non-diabetic Wistar-Clea rats were fed omega -3 (200 mg/kg/day) for 2 months and compared with untreated rats. Realtime PCR and immunoblotting were performed to determine Cx43, PKC- epsilon and PKC-delta expression. In situ Cx43 was examined by immunohistochemistry and subcellular alterations by electr on microscopy. Omega-3 intake reduced blood glucose, triglycerides, and cholesterol in diabetic rats and this was associated with improved integrity of cardiomyocytes and capillaries in the heart. Myocardial Cx43 mRNA and protein levels were higher in diab etic versus non- diabetic rats and were further enhanced by omega-3. The ratio of phosphorylated (functional) to non-phosphorylated Cx43 was lower in diabetic compared to non- diabetic rats but was increased by omega-3, in part due to up -regulation of PKC-epsilon. In addition, proapoptotic PKC-delta expression was decreased. In conclusion, spontaneously diabetic rats at an early stage of disease benefit from omega-3 intake due to its hypoglycemic effect, upregulation of myocardial Cx43, and preservation of cardiovascular ultrastructure. These findings indicates that supplementation of omega-3 may be beneficial also in the management of diabetes in humans., J. Radosinska, L. H. Kurahara, K. Hiraishi, C. Viczenczova, T. Egan Benova, B. Szeiffova Bacova, V: Dosenko, J. Navarova, B. Obsitnik, I. Imanaga, T. Soukup, N. Tribulova., and Obsahuje bibliografii
The study aimed to evaluate if the monitoring of advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), lipoperoxides (LPO) and interleukin-6 (IL-6) in plasma could help to predict development of diabetic complications (DC). Clinical and biochemical parameters including AGEs, AOPP, LPO and IL-6 were investigated in patients with type 2 diabetes mellitus (DM2) with (+DC) and without (-DC) complications. AGEs were significantly higher in both diabetic groups compared to controls. AGEs were also significantly higher in group +DC compared to -DC. AGEs significantly correlated with HbA1c. We observed significantly higher AOPP in both diabetic groups in comparison with controls, but the difference between -DC and +DC was not significant. LPO significantly correlated with BMI. IL-6 were significantly increased in both diabetic groups compared to controls, but the difference between -DC and +DC was not significant. There was no significant correlation between IL-6 and clinical and biochemical parameters. These results do not exclude the association between IL-6 and onset of DC. We suggest that the measurement of not only HbA1c, but also AGEs may be useful to predict the risk of DC development in clinical practice. Furthermore, the measurement of IL-6 should be studied as adjunct to HbA1c monitoring., V. Jakuš, E. Šándorová, J. Kalninová, B. Krahulec., and Obsahuje bibliografii
Monoamine oxidase (MAO, type A and B) and semicarbazide-sensitive amine oxidase (SSAO) metabolize biogenic amines, however, the impact of these enzymes in arteries from patients with type 2 diabetes remains poorly understood. We investigated the kinetic parameters of the enzymes to establish putative correlations with noradrenaline (NA) content and patient age in human mesenteric arteries from type 2 diabetic patients. The kinetic parameters were evaluated by radiochemical assay and NA content by high-performance liquid chromatography (HPLC). The activity of MAO-A and SSAO in type 2 diabetic vascular tissues was significantly lower compared to the activity obtained in non-diabetic tissues. In the correlation between MAO-A (Km) and NA content, we found a positive correlation for both the diabetic and non-diabetic group, but no correlation was established for patient age. In both groups, MAO-B (Vmax) showed a negative correlation with age. The results show that MAO-A and SSAO activities and NA content of type 2 diabetic tissues are lower compared to the non-diabetic tissues, while MAO-B activity remained unchanged. These remarks suggest that MAO-A and SSAO may play an import ant role in vascular tissue as well as in the vascular pathophysiology of type 2 diabetes., S. F. Nunes ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Acute streptozotocin diabetes mellitus (DM) as well as remote ischemic preconditioning (RPC) has shown a favorable effect on the postischemic-reperfusion function of the myocardium. Cardioprotective mechanisms offered by these experimental models involve the mitochondria with the changes in functional properties of membrane as the end-effector. The aim was to find out whether separate effects of RPC and DM would stimulate the mechanisms of cardioprotection to a maximal level or whether RPC and DM conditions would cooperate in stimulation of cardioprotection. Experiments were performed on male Wistar rats divided into groups: control, DM, RPC and DM treated by RPC (RPC+DM). RPC protocol of 3 cycles of 5-min hind limb ischemia followed by 5-min reperfusion was used. Ischemicreperfusion injury was induced by 30-min ischemia followed by 40-min reperfusion of the hearts in Langendorff mode. Mitochondria were isolated by differential centrifugation, infarct size assessed by staining with 1 % 2,3,5-triphenyltetrazolium chloride, mitochondrial membrane fluidity with a fluorescent probe DPH, CoQ9 and CoQ10 with HPLC. Results revealed that RPC as well as DM decreased the infarct size and preserved mitochondrial function by increasing the mitochondrial membrane fluidity. Both used models separately offered a sufficient protection against ischemic-reperfusion injury without an additive effect of their combination., M. Ferko, I. Kancirová, M. Jašová, I. Waczulíková, S. Čarnická, J. Kucharská, O. Uličná, O. Vančová, M. Muráriková, T. Ravingerová, A. Ziegelhöffer., and Obsahuje bibliografii
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