Annona and ginger have prominent uses in traditional medicine; their therapeutic properties have not been sufficiently explored. The ameliorative effect of Annona or ginger extracts on hyperglycaemia associated with oxidative stress, inflammation, and apoptosis in experimentally induced diabetes was addressed. Type 1 diabetes in male rats was induced by a single injection of streptozotocin (STZ; 40 mg/kg, i.p.), then Annona (100 mg/kg) or ginger (200 mg/kg) extracts were orally administered daily for 30 days. The Annona and ginger extracts ameliorated hyperglycaemia, insulin level, glycosylated haemoglobin (HbA1c) and insulin resistance (HOMA-IR) levels in the diabetic rats. The treatments significantly ameliorated liver function enzymes and total proteins; this was confirmed by histopathological examination of liver sections. Annona and ginger extracts significantly reduced elevated malondialdehyde (MDA) and restored activity of antioxidant enzymes in the liver such as glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) and the hepatic content of reduced glutathione (GSH). The oxidative stressdependent inflammation was regulated by both Annona and ginger extracts, which was indicated by down-regulation of TNF-α, NF-κB, pro-apoptotic proteins Bax, p53, and anti-apoptotic protein Bcl-2. Moreover, the expression of insulin receptor (INSR) and glucose transporter 2 (GLUT2) genes was markedly regulated by both these extracts. The results suggest that Annona and ginger extracts ameliorate the hepatic damage resulting from diabetes by advocating antioxidants and modulating apoptotic mediator proteins in the liver of diabetic rats. In conclusion, Annona and ginger extracts have a potential therapeutic effect in the treatment of diabetes and its complications.
This study investigates the effects of long-term treatment with sulodexide (SLX) on norepinephrine (NE)-induced contractions, acetylcholine(Ach)-induced relaxations, acute cyclooxygenase blockade by diclofenac (DIC) in isolated femoral arteries (FA) and the parameters of oxidative phosporylation in liver mitochondria. 15-weeks old Wistar rats were divided into four groups: control (C; injected with saline solution), treated control (C+SLX), diabetic (DM) and treated diabetic (DM+SLX). Diabetes was induced with a single i.v. dose of streptozotocin (STZ) 45 mg.kg-1. SLX was administered i.p., at dose 100 IU.kg-1 daily for 5 weeks. Vascular responses of isolated femoral arteries were measured using Mulvany-Halpern myograph. Respiratory function of the mitochondria was determined using voltamperometric method on oxygraph Gilson. In diabetic rats the amplitude of maximal response to NE was elevated. DIC pretreatment decreased the amplitudes of NE-induced contractions in all groups of rats. SLX treatment decreased sensitivity of FA to NE and caused higher relaxatory responses to Ach in C and DM. Oxygen consumption and phosphorylation rates ([QO2(S3)], [QO2(S4)] and (OPR)) and respiratory control ratio (RCR) were decreased in the mitochondria of DM rats. Mitochondria of C rats were not affected with SLX treatment. Administration of SLX in DM rats was associated with increase of RCR, other parameters were not affected. Our findings suggest that SLX treatment might be associated with vasculoprotective effects during diabetes and improvement of mitochondrial function., L. Dobiaš, M. Petrová, R. Vojtko, O. Uličná, O. Vančová, V. Kristová., and Obsahuje bibliografii
The aim of this study was to explore the changes in the adipokines leptin and adiponectin in obese patients with type 1 diabetes mellitus (T1DM) who underwent seven days of fasting and 21 days of low-calorie diet (LCD). The plasma leptin and adiponectin concentrations were measured in 14 obese patients with T1DM at baseline, immediately after 7 days of fasting, and after 21 days of LCD. 13 non-obese patients with T1DM were studied only after an overnight fasting. Bioimpedance technique was used for determination of body composition. Obese T1DM patients lost 6.0 kg (6.0; 6.8) (median, 25 %; 75 %) and decreased their fat tissue after fasting and LCD. Plasma leptin in obese T1DM was significantly higher than in non-obese T1DM patients: 9.10 (5.06; 25.89) vs. 1.71 (1.12; 7.08) μg ∙ l-1 and transiently decreased immediately after fasting: 3.45 μg ∙ l-1 (1.47; 7.00), (P<0.05). Adiponectin/leptin ratio in obese T1DM was significantly lower than in non-obese T1DM patients: 0.67 (0.57; 1.49) vs. 3.50 (2.46; 6.30) ∙ 103 and transiently increased immediately after fasting: 2.22 (1.26; 3.24) ∙ 103, (P<0.05). We conclude that obese patients with T1DM are characterized by hyperleptinemia that is reduced by prolonged fasting, but only slightly affected by low calorie diet., F. Musil, V. Blaha, A. Ticha, R. Hyspler, M. Haluzik, J. Lesna, A. Smahelova, L. Sobotka., and Obsahuje bibliografii
Diabetes mellitus (DM) has been known for many years to be associated with poor cardiovascular prognosis. Due to the sensitive neuropathy, the coronary artery disease in diabetic patients is frequently asymptomatic. Also twelve leads resting ECG can be within normal limits even in an advanced stage of coronary artery disease. Therefore in addition to the standard ECG other electrocardiographic procedures started to be studied in order to find some typical signs of myocardial damages caused by DM. Repeatedly reported results showed in DM patients without cardiovascular complications the tachycardia, shortening of the QRS and QT intervals, increase of the dispersion of QT interval, decreased amplitudes of depolarization waves, shortened activation time of ventricular myocardium and a flattening of T waves confirmed by the lower value of maximum and minimum in repolarization body surface isopotential maps. Most of these changes are even more pronounced in patients with cardiac autonomic neuropathy. Comparison with similar ECG changes in other diseases suggests that the electrocardiographic changes in DM patients are not specific and that they are particularly caused by an increased tone of the sympathetic nervous system what was indirectly confirmed by the heart rate variability findings in these patients., O. Kittnar., and Obsahuje bibliografii
Cortisone acetate test was performed in twelve young adult patients with diabetes mellitus type 1, after dexamethasone administration to suppress endogenous cortisol production. Previous screening revealed that all of the subjects had peak cortisol responses in the range from subnormal to normal, as determined by a low-dose Synacthen test. The aim was to find out whether these patients would exhibit different conversion of cortisone to cortisol by 11β-hydroxysteroid dehydrogenase. Using multifactorial ANOVA the following significant relationships were obtained between cortisol or cortisol/cortisone ratio measured during the test and other para meters examined a) before dexamethasone suppression and b) du ring the test: a) Cortisol at 120 th minute negatively correlated with daily insulin dose and positively with basal aldosterone. Cortisol/cortisone ratio at 60th, 120th, 180th, and 240th minute negatively correlated with basal aldosterone/plasma reni n activity ratio, urinary free cortisol/24 hours and positively with basal dehydroepindrosterone sulphate. b) Cortisol at 120th minute negatively correlated with suppressed basal serum glycemia; cortisol/cortisone ratio during the whole test negatively correlated with supressed basal ACTH. The examination of peripheral metabolism of cortisol using cortisone acetate test in patients with di abetes mellitus type 1 showed adaptive changes of 11β-hydroxysteroid dehydrogenace activity associated with altered cortisol tissue supply., K. Šimůnková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Objective: To examine the impact of family history of diabetes mellitus 2 (DM 2) on insulin sensitivity and secretion in lean women with polycystic ovary syndrome (PCOS). Thirteen healthy women (C), 14 PCOS without family history of DM 2 (FH-) and 8 PCOS with family history of DM 2 (FH+) were examined using euglycemic hyperinsulinemic clamp and an arginine secretion test (insulin and glucagon at fasting glycemia (AIRFG and AGRFG) and at hyperglycemia (AIR14 and AG 14)). FH+ women were more insulin resistant than FH- with lower insulin sensitivity index corrected per lean body mass (p<0.05). They had significantly higher triglycerides (p<0.05) and lower HDL-cholesterol (p<0.05) than C or FH- women. Concerning insulin secretion, AIR FG was increased in FH+ women comparing FH- women (p<0.05). Disposition indices derived from AIRFG or AIR14 and insulin sensitivity index did not differ between FH+ or FH-. Thus, women with PCOS with the concomitant family history of DM 2 have lower insulin sensitivity than healthy control women. Insulin resistance observed in these women with PCOS is compensated by increased insulin secretion., J. Vrbíková, T. Grimmichová, K, Dvořáková, M. Hill, S. Stanická, K. Vondra., and Obsahuje bibliografii a bibliografické odkazy
The aim of our study was to evaluate rapid insulin pulses and insulin secretion regularity in fasting state in lean women with polycystic ovary syndrome (PCOS) in comparison to lean healthy women. PCOS (n=8) and controls (n=7) underwent every minute blood sampling for 60 min. Insulin pulsatility was assessed by deconvolution and insulin secretion regularity by approximate entropy methodology. PCOS had higher testosterone (p<0.02), prolactin (p<0.05) and lower sex hormone binding globulin (SHBG) (p<0.0006) levels than controls. Approximate entropy, insulin pulse frequency, mass, amplitude and interpulse interval did not differ between PCOS and controls. PCOS had broader insulin peaks determined by a common half-duration (p<0.07). Burst mass correlated positively with testosterone (p<0.05) and negatively with SHBG (p<0.0004) and common half-duration correlated positively with prolactin (p<0.008) and cortisol levels (p<0.03). Approximate entropy positively correlated with BMI (p<0.04) and prolactin (p<0.03). Lean PCOS patients tended to have broader insulin peaks in comparison to healthy controls. Prolactin, androgens and cortisol might participate in alteration of insulin secretion in PCOS-affected women. Body weight and prolactin levels could influence insulin secretion regularity., T. Grimmichová, J. Vrbíková, P. Matucha, K. Vondra, P. P. Veldhuis, M. L. Johnson., and Obsahuje bibliografii a bibliografické odkazy
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