Current knowledge suggests a complex role of C-peptide in human physiology, but its mechanism of action is only partially understood. The effects of C-peptide appear to be variable depending on the target tissue, physiological environment, its combination with other bioactive molecules such as insulin, or depending on its concentration. It is apparent that C-peptide has therapeutic potential for the treatment of vascular and nervous damage caused by type 1 or late type 2 diabetes mellitus. The question remains whether the effect is mediated by the receptor, the existence of which is still uncertain, or whether an alternative non-receptor-mediated mechanism is responsible. The Institute of Endocrinology in Prague has been paying much attention to the issue of C-peptide and its metabolic effect since the 1980s. The RIA methodology of human C-peptide determination was introduced here and transferred to commercial production. By long-term monitoring of C-peptide oGTT-derived indices, the Institute has contributed to elucidating the pathophysiology of glucose tolerance disorders. This review summarizes the current knowledge of C-peptide physiology and highlights the contributions of the Institute of Endocrinology to this issue., Daniela Vejrazkova, Marketa Vankova, Petra Lukasova, Josef Vcelak, Bela Bendlova., and Obsahuje bibliografii
Lipoprotein (a) [Lp(a)] is an LDL-like particle that contains an apolipoprotein B100 molecule covalently bound to a plasminogen-like glycoprotein, apolipoprotein (a) [apo(a)]. Epidemiological evidence supports a direct and causal association between Lp(a) levels and coronary risk. On the contrary, a few prospective findings demonstrate inverse association of Lp(a) levels with risk of type 2 diabetes (T2DM). The aim of our study was to evaluate the association of Lp(a) with indicators of insulin resistance (IR) and metabolic syndrome (MS), which precede development of T2DM. We enrolled 607 asymptomatic dyslipidemic subjects (295 men and 312 women, mea n age 45.6±14.0 years) into our cross-sectional study. Lp(a) concentrations correlated inversely with TG, AIP, insulin, HOMA, C-peptide, BMI, waist circumference, and number of MS components (p<0.01 for all). Subjects with MS had significantly lower Lp(a) concentrations in comparison with those without the presence of this phenotype (p<0.0001). Serum concentrations of Lp(a) in the lower (1th 3rd) quartiles of insulin and HOMA were significantly higher than in the 4 th quartile of these insulin resistance markers (p<0.001). Odds ratios of having increased markers of IR (TG, HOMA) and MS in top quartile of Lp(a) also indicate inverse association of Lp(a) with IR. The results of our study support an inverse association of Lp(a) levels with IR and MS that precedes overt T2DM diagnosis., H. Vaverková, D. Karásek, M. Halenka, L. Cibíčková, V. Kubíčková., and Obsahuje bibliografii
In experimental and human diabetes mellitus, evidence for an impaired function of the vascular endothelium has been found and has been suggested to contribute to the development of vascular complications in this disease. The aim of the study was to evaluate possible regional hemodynamic in vivo differences between healthy and diabetic rats which would involve nitric oxide (NO). Central hemodynamics and regional blood flow (RBF) were studied using radioactive microspheres in early streptozotocin (STZ)-diabetic rats and compared to findings in healthy control animals. This method provides a possibility to study the total blood flow and vascular resistance (VR) in several different organs simultaneously. L-NAME iv induced widespread vasoconstriction to a similar extent in both groups. In the masseter muscle of both groups, acetylcholine 2 μg/kg per min, induced a RBF increase, which was abolished by pretreatment with L-NAME, suggesting NO as a mediator of vasodilation. In the heart muscle of both groups, acetylcholine alone was without effect while the combined infusion of acetylcholine and L-arginine induced an L-NAME-sensitive increase in RBF. The vasodilation induced by high-dose acetylcholine (10 μg/kg per min) in the kidney was more pronounced in the STZ-diabetic rats. The results indicate no reduction in basal vasodilating NO-tone in the circulation of early diabetic rats. The sensitivity to vasodilating effects of acetylcholine at the level of small resistance arterioles vary between tissues but was not impaired in the diabetic rats. In the heart muscle the availability of L-arginine was found to limit the vasodilatory effect of acetylcholine in both healthy and diabetic rats. In conclusion, the results indicate a normal action of NO in the investigated tissues of the early STZ-diabetic rat., E. Granstam, S.-O. Granstam., and Obsahuje bibliografii
Arterial sites with low wall shear stress (WSS) are more prone to the development of atherosclerotic plaques, as was observed in carotid arteries in subjects with atherosclerosis risk factors. Type 2 diabetes mellitus (DM), hypertension, hyperlipidemia and other components of the metabolic syndrome, are associated with high risk for symptomatic cerebrovascular disease. It was shown by others that untreated type 2 DM is associated with lower WSS in common carotid arteries. However, the cardiovascular risk of type 2 DM could be modified by therapy. The aim of our study was to test the hypothesis that treated type 2 DM subjects with metabolic syndrome still have lower WSS in common carotid arteries than healthy controls. We enrolled 26 compensated DM subjects with metabolic syndrome, treated by metformin, statins and ACEI for more than 6 months, and 22 aged-comparable healthy controls. Wall shear rate (WSR) was used as a measure of WSS. A linear 3-11 MHz probe was used to measure blood velocity and internal diameter in the common carotid arteries. We compared observed values of WSR adjusted for age by ANCOVA. Wall shear rate was significantly lower in DM group than in control subjects: peak (systolic) values of wall shear rate were 410±130 s-1 vs. 487±111 s-1 (p<0.005). DM subjects had significantly lower WSR, because of both thinner lumen and slower blood flow velocities. Lower WSR was accompanied by higher IMT (0.73±0.12 mm vs. 0.64±0.11 mm, p<0.001). Treated subjects with compensated type 2 DM with metabolic syndrome still have atherogenic hemodynamic profile. These findings might help to understand faster progression of atherosclerosis in diabetic subjects with metabolic syndrome despite up-to-date medication., E. Chytilová ...[et al.]., and Obsahuje seznam literatury
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