The Impact of DJOS Surgery, a High Fat Diet and a Control Diet on the Enzymes of Glucose Metabolism in the Liver and Muscles of Sprague-Dawley Rats

The prevalence of diabetes type 2 (T2DM) and obesity is growing exponentially and becoming a global public health problem. The enzymes of glucose metabolism play a role in the pathogenesis of insulin resistance and T2DM. A pathophysiological link between different dietary patterns, HFD, obesity, T2DM and the enzymes of glucose metabolism can be used as a potential target in therapeutic strategies for the treatment of obesity, and T2DM. The aim of this study was to measure the impact of DJOS bariatric surgery and different types of dietary patterns on glycogen synthase kinase 3 α (GSK-3α), glycogen phosphorylase (PYGM, PYGL), and phosphofructokinase (PFK-1) concentrations in liver and soleus muscle tissues of rats. After 8 weeks on a high-fat diet (HF) or control diet (CD), rats underwent duodenal-jejunal omega switch (DJOS) or SHAM (control) surgery. After surgery, for the next 8 weeks, half of DJOS/SHAM animals were kept on the same diet as before, and half had a changed diet. The concentrations of GSK-3α, PYGM, PYGL and PFK-1 were measured in the soleus muscles and livers of the Sprague-Dawley rats. The type of diet applied before/after surgery had stronger impact on levels of selected metabolic enzymes than DJOS or SHAM surgery. The impact of DJOS surgery was visible for GSK-3α and PYGL concentration in the liver but not in the soleus muscle tissue. The type of bariatric surgery had an impact on liver GSK-3α concentration in all studied groups except the CD/CD group, where the impact of diet was stronger. DJOS bariatric surgery influenced the level of PYGL in the livers of rats maintained on the CD/CD diet but not from other groups. The dietary patterns applied before and after bariatric surgery, had a stronger impact on enzymes’ concentrations than DJOS surgery, and the strong, deleterious effect of an HF was observed. A change of the diet per se showed a negative impact on the enzymes’ tissue concentration

Aktywność enzymów antyoksydacyjnych i stężenie aldehydu dimalonowego jako wykładniki stresu oksydacyjnego u kobiet z subkliniczną nieautoimmunologiczną nadczynnością tarczycy

Introduction: The recent investigations point out the significant role of oxidative stress in the development of thyroid gland disease. The present study was designed to investigate the variation of oxidative stae in women with non-autoimmunological subclinical hyperthyroidism. Material and methods: The study was conducted on 20 females with non-autoimmunological subclinical hyperthyroidism and 15 healthy women. Manganase-containing superoxide dismutase (Mn-SOD) and extracellular superoxide dismutase (EC-SOD) plasma activity, and malondialdehyde (MDA) plasma concentration were measured. Results: EC-SOD plasma activity was significantly higher in women with subclinical hyperthyroidism when compared with the control group (13.3 &#177; 2.1 vs. 10.9 &#177; 1.4 NU/ml; p < 0.05), unlike Mn-SOD (4.2 &#177; 0.5 vs. 4.0 &#177; 1.0 NU/ml). MDA plasma concentration increased significantly in women with subclinical hyperthyroidism (3.5 &#177; 1.2 vs. 2.0 &#177; 0.6 &#956;mol/l; p < 0.05). Conclusions: The increased EC-SOD plasma activity may reflect disturbances of oxidative state in subclinical hyperthyroidism. Parallel increase of MDA plasma concentration may indicate enhancement of lipid peroxidationin in patients with subclinical hyperthyroidism.Wstęp: Badania z ostatnich lat wskazują na udział stresu oksydacyjnego w rozwoju schorzeń gruczołu tarczowego. Celem niniejszej pracy jest ocena zmian stanu oksydacyjnego u kobiet z subkliniczną nieautoimmunologiczną nadczynnością tarczycy. Materiał i metody: Badania przeprowadzono u 20 kobiet z subkliniczną nadczynnością tarczycy oraz u 15 zdrowych kobiet. Wykonywano oznaczenia aktywności dysmutazy ponadtlenkowej - izoformy manganowej (Mn-SOD) i miedziowo-cynkowej (EC-SOD), a także stężenia aldehydu dimalonowego (MDA) w osoczu. Wyniki: U kobiet z subkliniczną nadczynnością tarczycy stwierdzono w osoczu wyższą w porównaniu z grupą kontrolną aktywność ECSOD (13,3 &#177; 2,1 vs. 10,9 &#177; 1,4 NU/ml; p < 0,05), natomiast aktywności Mn-SOD nie różniły się pomiędzy grupami (4,2 &#177; 0,5 vs. 4,0 &#177; 1,0 NU/ml). Badania wykazały również, że u kobiet z nadczynnością tarczycy w porównaniu z grupą kontrolną występuje wyższe stężenie MDA w osoczu niż w grupie kobiet zdrowych (3,5 &#177; 1,2 vs. 2,0 &#177; 0,6 &#956;mol/l; p < 0,05). Wnioski: W grupie chorych z subkliniczną nadczynnością tarczycy występują zaburzenia równowagi oksydacyjnej, przejawiające się wzrostem aktywności EC-SOD w osoczu. Towarzyszy temu podwyższone stężenie MDA, świadczące o nasileniu peroksydacji lipidów w tej grupie chorych

Changes in Liver Gene Expression and Plasma Concentration of Rbp4, Fetuin-A, and Fgf21 in Sprague-Dawley Rats Subjected to Different Dietary Interventions and Bariatric Surgery

Purpose. To study the effect of duodenal-jejunal omega switch (DJOS) in combination with different dietary patterns on the retinolbinding protein (RBP4), fetuin-A, and fibroblast growth factor 21 (FG F21) plasma levels and their hepatic gene expressions in rats. Methods. A high-fat diet (HF) was given to 28 rats and 28 more were fed with a control diet (CD) for 2 months. After that, half of each group underwent either DJOS or SHAM surgery. For the next 2 months, half of the animals in each operation group were kept on the same diet as before and half of them had the diet changed. After 16 weeks of the experiment RBP4, fetuin-A, and FGF21 plasma levels as well as liver Rbp4, Ahsg, and Fgf2I gene expressions were measured. Results. DJOS had a reductive impact on plasma levels of RBP4, fetuin-A, and FGF21 and Rbp4, Ahsg, and Fgf21 relative gene expression in the liver when compared to SHAM. The HF/HF group expressed significantly higher RBP4 and fetuin-A plasma levels in comparison to the control. The HF diet used before and/or after surgery led to upregulation of Rbp4, Ahsg, and Fgf2I relative gene expression. The lowest levels of analyzed parameters were observed in the CD/CD group. Conclusions: The efficiency of DJOS surgery, measured by hepatokines' plasma levels and their gene expressions in the liver, depends on the type of diet applied before and after surgery. Manipulation of dietary patterns can lead to marked improvements in metabolic profile after DJOS surgery

Centrally injected histamine increases posterior hypothalamic acetylcholine release in hemorrhage-hypotensive rats

Histamine, acting centrally as a neurotransmitter, evokes a reversal of hemorrhagic hypotension in rats due to the activation of the sympathetic and the renin-angiotensin systems as well as the release of arginine vasopressin and proopiomelanocortin-derived peptides. We demonstrated previously that central nicotinic cholinergic receptor's are involved in the pressor effect of histamine. The aim of the present study was to examine influences of centrally administrated histamine on acetylcholine (ACh) release at the posterior hypothalamus a region characterized by location of histaminergic and cholinergic neurons involved in the regulation of the sympathetic activity in the cardiovascular system in hemorrhage-hypotensive anesthetized rats. Hemodynamic and microdialysis studies were carried out in Sprague-Dawley rats. Hemorrhagic hypotension was induced by withdrawal of a volume of 1.5 ml blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP), heart rate (HR), and an increase in extracellular posterior hypothalamic ACh and choline (Ch) levels by 56% and 59%, respectively. Intracerebroventricularly (icy.) administered histamine (50, 100, and 200 nmol) dose- and time-dependently increased MAP and HR and caused an additional rise in extracellular posterior hypothalamic ACh and Ch levels at the most by 102%, as compared to the control saline-treated group. Histamine H1 receptor antagonist chlorpheniramine (50 nmol; i.c.v.) completely blocked histamine-evoked hemodynamic and extracellular posterior hypothalamic ACh and Ch changes, whereas H2 and H3/H4 receptor blockers ranitidine (50 nmol; i.c.v.) and thioperamide (50 nmol; i.c.v.) had no effect

The mediation of the central histaminergic system in the pressor effect of intracerebroventricularly injected melittin, a phospholipase A(2) activator, in normotensive rats

Melittin is a polypeptide component of bee venom that leads to an increase in arachidonic acid release and subsequently in prostaglandin synthesis by activating phospholipase A(2). Recently we demonstrated that centrally or peripherally administrated melittin caused pressor effect and central thromboxane A(2) (TXA(2)) and cholinergic system mediated these effects of melittin. Also centrally injected histamine leads to pressor and bradycardic response by activating central histamine receptors in normotensive rats and central cholinergic system involved the effects of histamine. The present study demonstrates an involvement of the central histaminergic system in melittin-induced cardiovascular effect in normotensive rats. Experiments were carried out in male Sprague Dawley rats. Intracerebroventricularly (i.c.v.) injected melittin (0.5, 1 and 2 nmol) caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR) as we reported previously. Moreover, H-2 receptor antagonist ranitidine (50 nmol; icy.) almost completely and H-3/H-4 receptor antagonist thioperamide (50 nmol; i.c.v.) partly blocked melittin-evoked cardiovascular effects, whereas H-1 receptor blocker chlorpheniramine (50 nmol; icy.) had no effect. Also centrally injected melittin was accompanied by 28% increase in extracellular histamine concentration in the posterior hypothalamus, as shown in microdialysis studies. In conclusion, results show that centrally administered melittin causes pressor and bradycardic response in conscious rats. Moreover, according to our findings, there is an involvement of the central histaminergic system in melittin-induced cardiovascular effects

The influence of neuropeptide Y on the cardiovascular regulation

In this review we present influences of the neuropeptide Y (NPY), a 36-amino acid peptide which belongs to the pancreatic polypeptide family, on the central and peripheral cardiovascular regulation. NPY has been detected in many central nervous system areas, including arcuate and paraventricular nuclei of the hypothalamus, nucleus of the solitary tract (NTS) and rostral ventral-lateral medulla (RVLM). Moreover, it is released from postganglionic neurons of the sympathetic nervous system and platelets. Both at the central and peripheral level, NPY acts as a peptide neuromodulator secreted together with classical neurotransmitters. It influences the cardiovascular center function acting directly on RVLM and hypothalamic neurons and indirectly – via regulation of the baroreceptor reflex sensitivity at NTS level. Interestingly, the activation of different types of NPY receptors in different central nervous system areas can cause various, even opposite, effects in the cardiovascular regulation. There is an increase in NPY synthesis and release in conditions of disturbed circulatory homeostasis, for instance in haemorrhagic shock. In critical haemorrhagic hypotension, NPY probably activates compensatory mechanisms leading to maintenance of blood pressure values necessary to survive. Thus, we conclude that further studies are needed to clarify NPY functions in conditions of hyper- and hypotension.W niniejszej pracy przedstawiono wpływ neuropeptydu Y (NPY), peptydu zbudowanego z 36 aminokwasów, należącego do rodziny polipeptydów trzustkowych, na ośrodkową oraz obwodową regulację układu krążenia. NPY jest obecny w wielu obszarach ośrodkowego układu nerwowego, takich jak jądra łukowate, przykomorowe podwzgórza, jądro pasma samotnego (NTS) czy też przednia brzuszno-boczna część rdzenia przedłużonego (RVLM). Ponadto jest on uwalniany z pozazwojowych neuronów układu współczulnego oraz z płytek krwi. NPY działa zarówno w ośrodkowym, jak i obwodowym układzie nerwowym jako neuromodulator uwalniany łącznie z klasycznymi neurotransmiterami. Wpływa on na funkcje ośrodka sercowo-naczynioruchowego w sposób bezpośredni, działając na RVLM oraz neurony podwzgórza, jak również pośrednio, poprzez wpływ na czułość odruchu z baroreceptorów tętniczych na poziomie NTS. Co ciekawe, aktywacja różnych typów receptorów NPY w ośrodkowym układzie nerwowym może powodować różne, a nawet przeciwstawne efekty w regulacji czynności układu krążenia. W stanie zaburzonej homeostazy krążeniowej, np. podczas wstrząsu krwotocznego, dochodzi do wzrostu syntezy i uwalniania NPY, który prawdopodobnie aktywuje mechanizmy kompensacyjne prowadzące do utrzymania niezbędnych do przeżycia wartości ciśnienia krwi. Przedstawiona analiza wskazuje na konieczność prowadzenia dalszych badań nad rolą NPY w stanie hiper- i hipotensji

Influence of thyroliberin on central cardiovascular regulation

Thyroliberin (thyrotropin releasing hormone – TRH) is a tripeptide synthesized mainly in the paraventricular nucleus of the hypothalamus. It is a component of the hypothalamic–pituitary–thyroid axis, in which it intensifies the synthesis and secretion of the thyroid stimulating hormone. It also regulates the release of other hormones (prolactin, vasopressin) and neurotransmitters in the central nervous system (noradrenaline and adrenaline). Acting as a neuromodulator, TRH affects many functions of the central nervous system. In the present review, we demonstrate interactions between the thyroliberinergic system and other neuronal systems, especially the role of TRH in the central cardiovascular regulation. The differences between TRH-induced effects in normotension, hypertension and hypotension have been presented.Tyreoliberyna (thyrotropin releasing hormone – TRH) to tripeptyd syntetyzowany głównie w jądrze przykomorowym podwzgórza. Jest składową osi podwzgórze–przysadka–tarczyca, w której nasila procesy syntezy i wydzielania hormonu tyreotropowego. Wpływa także na uwalnianie innych hormonów (prolaktyna, wazopresyna) i neuroprzekaźników w ośrodkowym układzie nerwowym (noradrenalina i adrenalina). Działając jako neuromodulator, TRH wpływa na wiele funkcji ośrodkowego układu nerwowego. W pracy przedstawiono współzależności między układem tyreoliberynergicznym a innymi układami neuronalnymi, ze szczególnym uwzględnieniem znaczenia THR w ośrodkowej regulacji układu krążenia. Zwrócono uwagę na różnice w działaniu TRH w stanach normotensji, hipertensji oraz hipotensji