Obesity in T1DM patients is associated with the components of metabolic syndrome. The influence of controlled fasting and low calorie diet (LCD) on insulin sensitivity and glucose metabolism was studied in 14 obese patients with type 1 diabetes mellitus (T1DM) (42.6±9.4 years, BMI 32.4±2.1 kg m−2). Insulin sensitivity in obese T1DM patients was measured using a hyperinsulinemic-euglycemic clamp before fasting, immediately after 7 days of fasting, and after 21 days of LCD. Glucose oxidation and non-oxidative glucose disposal were measured before and during the clamp by indirect calorimetry. In the control group of 13 of non-obese T1DM patients (36.9±13.9 years, BMI 22.6±2.1 kg m−2), only one hyperinsulinemiceuglycemic clamp was performed. Obese T1DM patients lost 6.1±1.1 kg after fasting and maintained reduction in body weight after 21 days of LCD. Fasting transiently reduced insulinmediated glucose disposal in the clamp (from 9.69±1.48 to 6.78±1.21 mg min−1 kg−1, P<0.001). This was caused by reduced glucose oxidation after the fasting period (from 2.81±0.52 to 0.88±0.98 mg min−1 kg−1, P<0.001). We conclude that one week of fasting transiently decreased insulin-mediated glucose disposal in T1DM patients. This was caused by reduced glucose oxidation., F. Musil, ... [et al.]., and Obsahuje seznam literatury
The present investigation was directed to study the effect of in vitro or ex vivo NO donors, sodium nitroprusside and molsidomine, using isolated sliced adipose tissue or in the form of immobilized and perfused adipocytes on the basal and isoprenaline-stimulated lipolysis. The results demonstrated that 1) in vitro application of sodium nitroprusside to perfused adipocytes or molsidomine to sliced adipose tissues affects isoprenaline-induced lipolysis in two ways, an increase in lipolysis at low isoprenaline concentrations (which means the sensitization of adipose tissues to adrenergic effect by NO) and decreased adrenergic agonist-stimulated lipolysis at higher concentration of isoprenaline (a decrease in the maximum lipolytic effect of isoprenaline), 2) low concentrations of molsidomine alone induced lipolysis from adipose tissue which attained more than 60 % of that by isoprenaline (pD2 value for molsidomine = 11.2, while pD2 for isoprenaline = 8.17) while sodium nitroprusside did not affect the basal lipolysis significantly, 3) in vivo administration of molsidomine for 2 days reduced the maximum lipolytic effect of isoprenaline and (only non-significantly) increased the sensitivity to low doses of isoprenaline. In conclusion the present data demonstrate that NO plays an important role in adrenergic lipolysis in adipose tissues and further investigations are needed to unravel the exact role of NO in lipolysis., D. Lincová, D. Mišeková, E. Kmoníčková, N. Canová, H. Farghali., and Obsahuje bibliografii
Thiazolidinediones are insulin-sensitizing drugs acting through peroxisome proliferator- activated receptor (PPAR)-γ. The aim of our study was to evaluate the effect of 5-month treatment with PPAR-γ agonist – rosiglitazone (4 mg/day), on the circulating markers of endothelial dysfunction and to evaluate the role of changes in endocrine function of adipose tissue in this process. Biochemical and metabolic parameters, circulating adiponectin, resistin, ICAM-1, VCAM-1, E-selectin, P-selectin, PAI-1, myeloperoxidase (MPO), and matrix metalloproteinase-9 (MMP-9) concentrations were assessed in 10 women with type 2 DM before and after rosiglitazone treatment and in a control group of healthy women. At baseline, diabetic group had significantly higher serum concentrations of glucose, glycated hemoglobin, V-CAM and PAI-1 compared to control group. Adiponectin levels tended to be lower in diabetic group, while resistin concentrations did not differ from control group. Rosiglitazone treatment improved diabetes compensation, significantly reduced VCAM-1, PAI-1 and E-selectin concentrations and increased adiponectin levels, while it did not affect serum resistin concentrations. Adiponectin concentrations at baseline were inversely related to E-selectin and MPO levels, this correlation disappeared after rosiglitazone treatment. We conclude that 5-month rosiglitazone treatment significantly reduced several markers of endothelial dysfunction. This effect could be at least in part attributable to marked increase of circulating adiponectin levels., R. Doležalová, M. M. Haluzík, L. Bošanská, Z. Lacinová, Z. Kasalová, T. Štulc, M. Haluzík., and Obsahuje bibliografii a bibliografické odkazy
Baclofen is the only clinically available metabotropic GABAB receptor agonist. In our experiment, we tested the hypothesis that long-term baclofen administration can impair learning and memory in rats. The experiment consisted of three parts. In the first part of the study the drug was administered simultaneously with the beginning of the behavioral tests. In the second and third part of the experiment baclofen was administered daily for 14 days and for one month before the tests. In each part of the experiment, adult rats were randomly divided into four treatment groups. Three groups were given an injection of baclofen at doses of 1 mg/kg, 5 mg/kg, 10 mg/kg, while the fourth group was injected with saline. The injections were given after each session. Spatial learning and memory were tested using the Morris water maze, involving three types of tests: Acquisition, Probe, and Re-acquisition. This work reveals that baclofen did not affect spatial learning at any of the tested doses and regardless of the length of administration. Memory was observed to be affected, but only at the highest dose of baclofen and only temporarily. This conclusion is in line with previously published clinical cases., M. Holajová, M. Franěk., and Seznam literatury
Autophagy-lysosomal pathway is a cellular mechanism ensuring degradation of various macromolecules like proteins or triacylglycerols (TAG). Its disruption is related to many pathological states, including liver steatosis. We compared the effect of short- and long-established steatosis on the intensity of autophagy-lysosomal pathway in rat liver. The experiments were carried out on 3-month old Wistar rats fed standard (SD) or highfat diet for 2 (HF-2) or 10 (HF-10) weeks. HF diet administered animals accumulated an increased amount of TAG in the liver (HF-2→HF-10). Autophagy flux was up-regulated in HF-2 group but nearly inhibited after 10 weeks of HF administration. The expression of autophagy related genes was up-regulated in HF-2 but normal in HF-10. In contrast, total activities of two lysosomal enzymes, lysosomal lipase (LAL) and acid phosphatase, were unaffected in HF-2 but significantly increased in HF-10 groups. mRNA expression of lysosomal enzymes was not affected by the diet. We conclude that in a state of metabolic unbalance (steatosis), autophagy machinery and lysosomal enzymes expression are regulated independently. The accumulation of TAG in the liver is associated with the increase of total LAL activity and protein expression. In contrast, the autophagy response is bi-phasic and after rapid increase it is significantly diminished. This may represent an adaptive mechanism that counteracts the excessive degradation of substrate, i.e. TAG, and eliminate over-production of potentially hazardous lipiddegradation intermediates., Z. Papáčková, ... [et al.]., and Obsahuje seznam literatury
Benzodiazepines seem to be frequently abused in conjunction with opioids. Fluoxetine was reported to block morphine locomotor sensitization in rats. Sensitization has been implicated in some aspects of drug abuse. We have investigated the effect of alprazolam (0.25 mg/kg) and fluoxetine (5 mg/kg) on the development and expression of sensitization to the locomotor stimulant effect of morphine (10 mg/kg) in mice. Sensitization was produced by daily injections of morphine (10 mg/kg) for 10 days. There was a clear sensitization of locomotor activity produced by morphine in photocell activity cages but co-administration of alprazolam with morphine had no effect on the degree of sensitization. Alprazolam was also without effect on the expression of the sensitized response to morphine in mice sensitized with morphine alone. Fluoxetine partly reduced both the development and expression of morphine sensitization. In conclusion, the present experiments have not yielded evidence that alprazolam may influence the development or the expression of sensitization to morphine. However, they have corroborated and extended results indicating that fluoxetine can attenuate, to a certain level, the development and expression of morphine sensitization., M. Votava, M. Kršiak, V. Moravec., and Obsahuje bibliografii
The relationships between exercise and metabolites as well as between exercise and sarcoplasmic reticulum function were studied in gastrocnemius muscle of ovariectomized-trained rats. Prolonged moderate-intensity exercise, treadmill up-hill run for 90 min with a 10° incline, decreased the muscle glycogen content. Exercise until exhaustion further lowered the glycogen concentration to 13 % of the control, together with a significant decrease of ATP and glucose-6-phosphate concentrations. Also, Ag+-induced Ca2+release, measured in whole muscle homogenate, showed a 30 % reduction on exhaustion, while Ca2+ uptake was unaffected by this exercise. ATPase activities, of both homogenate and SR vesicles, and Ca2+ transport in the latter preparation were not altered on exhaustion. It could be concluded from these results that muscular fatigue in ovariectomized rats after aerobic exercise is caused by the change in energy supply and Ca2+ release from the SR, this latter possibly due to metabolites generated by the exercise., I. Gigli, L. E. Bussmann., and Obsahuje bibliografii
Toxic influence of high oxygen concentration on pulmonary function and structures has been known for many years. However, the influence of high oxygen concentration breathing on defensive respiratory reflexes is still not clear. In our previous experiments, we found an inhibitory effect of 100 % oxygen breathing on cough reflex intensity in healthy guinea pigs. The present study was designed to detect the effects of hyperoxia on cough reflex in guinea pigs with allergic airway inflammation. In the first phase of our experiment, the animals were sensitized with ovalbumin. Thirty-two sensitized animals were used in two separate experiments according to oxygen concentration breathing: 100 % or 50 % oxygen for 60 h continuously. In each experiment, one group of animals was exposed to hyperoxia, another to ambient air. The cough reflex was induced both by aerosol of citric acid before sensitization, then in sensitized animals at 24 h and 60 h of exposition to oxygen/air in awake animals, and by mechanical stimulation of airway mucosa in anesthetized animals just after the end of the experiment. In contrast to 50 % oxygen, 100 % oxygen breathing leads to significant decrease in chemically induced cough in guinea pigs with allergic inflammation. No significant changes were present in cough induced by mechanical stimulation of airways., M. Brozmanová, J. Hanáček, M. Tatár, A. Strapková, P. Szépe., and Obsahuje bibliografii
The present experiments were performed to evaluate if increased heart tissue concentration of fatty acids, specifically myristic, palmitic and palmitoleic acids that are believed to promote physiological heart growth, can attenuate the progression of unloading-induced cardiac atrophy in rats with healthy and failing hearts. Heterotopic abdominal heart transplantation (HTx) was used as a model for heart unloading. Cardiac atrophy was assessed from the ratio of the native- to-transplanted heart weight (HW). The degree of cardiac atrophy after HTx was determined on days 7, 14, 21 and 28 after HTx in recipients of either healthy or failing hearts. HTx of healthy hearts resulted in 23±3, 46±3, 48±4 and 46±4 % HW loss at the four time-points. HTx of the failing heart resulted in even greater HW losses, of 46±4, 58±3, 66±2 and 68±4 %, respectively (P<0.05). Activation of “fetal gene cardiac program” (e.g. beta myosin heavy chain gene expression) and “genes reflecting cardiac remodeling” (e.g. atrial natriuretic peptide gene expression) after HTx was greater in failing than in healthy hearts (P<0.05 each time). Exposure to isocaloric high sugar diet caused significant increases in fatty acid concentrations in healthy and in failing hearts. However, these increases were not associated with any change in the course of cardiac atrophy, similarly in healthy and post-HTx failing hearts. We conclude that increasing heart tissue concentrations of the fatty acids allegedly involved in heart growth does not attenuate the unloading-induced cardiac atrophy., M. Pokorný, I. Mrázová, J. Malý, J. Pirk, I. Netuka, Z. Vaňourková, Š. Doleželová, L. Červenková, H. Maxová, V. Melenovský, J. Šochman, J. Sadowski, L. Červenka., and Seznam literatury
Transthoracic echocardiography (TTE) has become an important modality for the assessment of cardiac structure and function in animal experiments. The acquisition of echocardiographic images in rats requires sedation/anesthesia to keep the rats immobile. Commonly used anesthetic regimens include intraperitoneal or inhalational application of various anesthetics. Several studies have compared the effects of anesthetic agents on echocardiographic parameters in rats; however, none of them examined the effects of different concentrations of inhalational anesthetics on echocardiographic parameters. Accordingly, the aim of this study was to examine the effects of different concentrations of isoflurane used for anesthesia during TTE examination in rats on basic echocardiographic parameters of left ventricular (LV) anatomy and systolic function. TTE examinations were performed in adult male Wistar rats (n=10) anesthetized with isoflurane at concentrations of 1.5-3 %. Standard echocardiograms were recorded for off-line analysis. An absence of changes in basic echocardiographic parameters of LV anatomy and systolic function was found under isoflurane anesthesia using concentrations between 1.5-2.5 %. An isoflurane concentration of 3 % caused a small, but statistically significant, increase in LV chamber dimensions without a concomitant change in heart rate or fractional shortening. For the purpose of TTE examination in the rat, our results suggest that isoflurane concentrations ≤ 2.5 % can be safely recommended., H. Říha ... [et al.]., and Obsahuje seznam literatury