Advanced glycation end-products (AGEs) are key players in pathogenesis of long-term vasc ular diabetes complications. Several enzymes such as fructosamine 3-kinase (FN3K) and glyoxalase I (GLO I) are crucial in preventing glycation processes. The aim of our study was to evaluate an association of FN3K (rs1056534, rs3848403) and GLO1 rs4746 polymorphisms with parameters of endothelial dysfun ction and soluble receptor for AGEs (sRAGE) in 595 diabetic and non-diabetic subjects. Genotypic and allelic frequencies of mentioned polymorphisms did not differ between subgroups. In diabetic patients significant differences were observed in sRAGE concentrations according to their rs1056534 and rs3848403 genotype. While GG and CG genotypes of rs1056534 with mutate d G allele were associated with significant decrease of sRAGE (GG: 1055±458 and CG: 983±363 vs. CC: 1796±987 ng/l, p<0.0001), in rs3848403 polymorphism TT genotype with mutated T allele was related with significant sRAGE increase (TT: 1365±852 vs. CT: 1016±401 and CC: 1087±508 ng/l, p=0.05). Significant differences in adhesion molecules were observed in genotype subgroups of GLO1 rs4746 polymorphism. In conclusion, this is the first study describing significant relationship of FN3K (rs1056534) and (rs3848403) polymorphisms with concentration of sRAGE in patients with diabetes., J. Škrha Jr., A. Muravská, M. Flekač, E. Horová, J. Novák, A. Novotný, M. Prázný, J. Škrha, J. Kvasnička, L. Landová, M. Jáchymová, T. Zima, M. Kalousová., and Obsahuje bibliografii
Type 1 diabetes mellitus (DM 1A) is an autoimmune disease belonging to the most frequent chronic diseases of the childhood and young adults. DM 1A results from immune-mediated destruction of the insulin-producing beta cells of the pancreas. It is a genetically determined disease and many genes or genetic regions were found to be associated with its induction. In addition to the insulin-dependent diabetes mellitus 1 (IDDM1) gene, which marks the HLA region, and IDDM2 which marks the insulin gene, significant associations of DM 1A to other IDMM genes or genetic regions we reported. We shortly review recent achievements in the field, and the state of current knowledge., D. Kantárová, M. Buc., and Obsahuje bibliografii a bibliografické odkazy
Metabolic disorders such as obesity, insulin resistance and other components of metabolic syndrome (MetS) are connected with birth weight. Low and high birth weight is associated with a higher risk of developing type 2 diabetes mellitus, the mechanism is not clear. In this study, we evaluated the association between birth weight and anthropometric as well as biochemical components of MetS in women with a history of gestational diabetes mellitus (GDM) in comparison with control women. In part of the GDM group, we re-evaluated metabolic changes over 5-8 years. Anthropometry, blood pressure, glucose metabolism during the 3-h oGTT, lipid profile, uric acid, thyroid hormones, and liver enzymes were assessed. From the analyzed components of MetS in adult women we proved the association of low birth weight (birth weight <25th percentile) with glucose processing, in particular among women with a history of GDM. Low birth weight GDM women revealed significantly higher postchallenge insulin secretion and lower peripheral insulin sensitivity. Re-examinations indicate this association persists long after delivery., D. Vejrazkova, P. Lukasova, M. Vankova, O. Bradnova, G. Vacinova, J. Vcelak, V. Cirmanova, K. Andelova, H. Krejci, B. Bendlova., and Obsahuje bibliografii
A large body of evidence has implicated reactive carbonyl compounds as glycotoxic mediators of carbonyl stress. This review is focused on the pathophysiological effects of α-oxoaldehydes in diabetes and related complications, summarizing the state-of-the-art on the endogenously produced carbonyls methylglyoxal, glyoxal and 3-deoxyglucosone, formed as glycolytic intermediates during metabolic conversion of glucose, via Maillard reaction by degradation of glycated proteins, and during lipid peroxidation process. Their role in the advanced glycation process and detrimental effects on vascular tissue are discussed., Z. Turk., and Obsahuje bibliografii a bibliografické odkazy
The aims of our study were to evaluate plasma levels of gut hormones in children with Type 1 diabetes mellitus (T1DM) in comparison with healthy contro ls and to corr elate plasma concentrations of gut hormones with blood biochemistry, markers of metabolic control and with anthropometric parameters. We measured postprandial levels of specific gut peptide hormones in T1DM children. Amylin, glucos e-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), ghrelin, leptin, pancreatic polypeptide (PP), and polypeptide YY (PYY) were assessed in 19 T1DM children and 21 healthy reference controls. Multiplex assay kit (LINCOplex®) was used for determination of the defined plasma hormone levels. T1DM subjects had significantly reduce d amylin (p<0.001) and ghrelin (p<0.05) levels, whereas GIP (p<0.05) was elevated when compared with healthy controls. Pl asma levels of other measured hormones did not differ statistically between the studied groups. Further analysis of T1DM patien ts demonstrated an association between body mass index and GL P-1 (r=0.4642; p<0.05), leptin (r=0.5151; p<0.05), and amylin (r=0.5193; p<0.05). Ghrelin levels positively correlated with serum HDL cholesterol (r=0.4760; p<0.05). An inverse co rrelation was demonstrated with triglycerides (TG) (r=-0. 5674; p<0.01), insulin dosage (r= -0.5366; p<0.05), and HbA1c% (r= -0.6864; p<0.01). Leptin was inversely correlated with TG (r= -0.6351; p<0.01). Stepwise regression analysis was performed to enlighten the predictive variables. Our study demonstrated an altered secretion pattern of gut peptide hormones in T1DM children. A close correlation was revealed between these peptides as well as with blood biochemistry, markers of me tabolic control and with anthropometric parameters. Further studies are essential to explore this issue in T1DM children., M. Huml ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Diabetes mellitus is associated with a variety of cardiovascular complications including impaired cardiac muscle function. The effects of insulin treatment on heart rate, body temperature and physical activity in the alloxan (ALX)-induced diabetic rat were investigated using in vivo biotelemetry techniques. The electrocardiogram, physical activity and body temperature were recorded in vivo with a biotelemetry sy stem for 10 days before ALX treatment, for 20 days following administration of ALX (120 mg/kg) and thereafter, for 15 days whilst rats received daily insulin. Heart rate declined rapi dly after administration of ALX. Pre-ALX heart rate was 321 ± 9 beats per minute, falling to 285 ± 12 beats per minute 15-20 days after ALX and recovering to 331±10 beats per minute 5-10 days after commencement of insulin. Heart rate variabilit y declined and PQ, QRS and QT intervals were prolonged after administration of ALX. Physical activity and body temperature declined after administration of ALX. Pre-ALX body temperature was 37.6 ± 0.1 °C, falling to 37.3 ± 0.1 °C 15-20 days after ALX an d recovering to 37.8±0.1 °C 5-10 days after commencement insulin. ALX-induced diabetes is associated with disturbances in heart rhythm, physical activity and body temperature that are variously affected during insulin treatment., F. C. Howarth ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Elevated levels of insulin have been reported to induce both an arterial vasodilation mediated by nitric oxide (NO), and vasoconstriction mediated by endothelin and reactive oxygen radicals. Metformin, used to control blood glucose levels in type 2 diabetes, has also been shown to cause NO-mediated dilation of conduit arteries. It is possible that these contradictory vascular effects are due to a non-direct action on arteries. Therefore, the direct effect of high levels of insulin and metformin infusion on resistance artery diameter was evaluated. Experiments were carried out on the anesthetized pig; blood flow and pressure were measured in the iliac artery. An adjustable snare was applied to the iliac above the pressure and flow measurement site to induce step decreases (3-4 occlusions at 5 min intervals were performed for each infusion) in blood flow, and hence iliac pressure, and the conductance (Δflow / Δpressure) calculated. Saline, insulin (20 and 40 mUSP/l/min), and metformin (1 μg/ml/min) were infused separately downstream of the adjustable snare and their effect on arterial conductance assessed. Insulin at both infusion rates and metformin caused a significant reduction in peripheral vascular conductance. In conclusion, hyperinsulinemia and metformin infusion constrict resistance arterial vessels in vivo., F. Markos, C. M. Shortt, D. Edge, T. Ruane-O'Hora, M. I. M. Noble., and Obsahuje bibliografii
PPAR-α agonists improve insulin sensitivity in rodent models of obesity/insulin resistance, but their effects on insulin sensitivity in humans are less clear. We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-α agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate. At baseline, body mass index, serum glucose, triglycerides, glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes, while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group (n=10). No differences were found in serum resistin levels between obese and control group. Fenofibrate treatment decreased serum triglyceride concentrations, while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration. Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment. All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration. We conclude that administration of PPAR-α agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus. The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-α expression in human liver and muscle., K. Anderlová, R. Doležalová, J. Housová, L. Bošanská, D. Haluzíková, J. Křemen, J. Škrha, M. Haluzík., and Obsahuje bibliografii a bibiografické odkazy
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