Insulin expression and action in the central nervous system

Nakon njegovog otkrića početkom dvadesetog veka, dugo je smatrano da se insulin isključivo sintetiše u pankreasu i da u centralni nervni sistem (CNS) dospeva prolaskom kroz krvno-moždanu barijeru. Međutim, razvojem molekularno-bioloških metoda potvrđeno je prisustvo iRNK za preporoinsulin, samog (prepro)insulina, kao i C-peptida u nekim regionima mozga. Time je višestruko potvrđeno da se insulin, osim u pankreasu, sintetiše i u CNS. Nakon otkrića da se i receptor za insulin eksprimira u CNS, ispitivanja su bila usmerena ka upoznavanju dejstva ovog hormona u mozgu. Pokazano je da je, između ostalog, uključen u kontrolu apetita, regulaciji reprodukcije, ali i procesa vezanih za učenje i konsolidaciju memorije. Takođe je utvrđeno da su poremećaji dejstva insulina u CNS povezani sa razvojem nekih neurodegenerativnih bolesti. Iako je većina pomenutih efekata prvobitno pripisana insulinu koji iz sistemske cirkulacije dospeva u CNS, sve više se dizajniraju studije koje su orijentisane isključivo ka upoznavaju funkcije insulina koji nastaje u mozgu. Do sada je pokazano da se produkcija insulina u hipotalamusu smanjuje tokom stresnih situacija, što se negativno odražava na sintezu hormona rasta u adenohipofizi i njegovu sekreciju u sistemsku cirkulaciju. Nasuprot tome, pokazano je da kratkotrajno gladovanje povećava ekspresiju insulina u neuronima istog moždanog regiona ali i da ovaj fenomen nije povezan sa povećanjem stope ugradnje glukoznih transportera u ćelijsku membranu, niti sinteze glikogena u astrocitima. Biće potrebno sprovesti dodatne studije kako bi se u većoj meri upoznala uloga insulina koji nastaje unutar CNS.After being discovered in the early twentieth century, insulin was long considered to be exclusively produced in the β-pancreatic cells. Therefore the presence of this hormone in the central nervous system (CNS) was accounted for solely by its transport across the blood-brain barrier. However, owing to the advances in molecular biological techniques, it was established that the preproinsulin mRNA, the (pre)prounsulin peptide and C-peptide were also present in the CNS parenchyma. These findings unequivocally proved that, in addition to the pancreas, insulin was also produced in the CNS. After discovery that the insulin receptor was also expressed in the brain, numerous studies aimed to discover the insulin actions within the CNS. It was found that insulin was involved in the control of appetite, reproduction, learning and memory consolidation. Moreover, it was confirmed that the impairment of insulin signaling within the certain brain regions was associated with various neurodegenerative disorders. Although these effects were initially assigned to the action of the insulin transported from the circulation into the CNS, more studies were designed to uncover the roles of insulin produced in the CNS. It has been shown so far that stress decreases hypothalamic insulin production which subsequently results in the decreased growth hormone production and its secretion form adenohypophysis. Furthermore, short-term fasting increased hypothalamic insulin expression in rats, albeit this phenomenon did not result in either increased glucose uptake nor glycogen production in this brain region. More studies are needed to fully elucidate the role of the centrally produced insulin

Business of the Tourism Economy Enterprise in the Light of Socio- Economic Conditions

The aim of the research was to examine the correlation between the socioeconomic variables of employees (gender, age, level of education, monthly personal income of the respondents and monthly personal income of the respondent household, number of household members and number of household members who generate income) and opinion of respondents on the impact of activity assumed on their work and the work of other employees in their company, opinions on clients’ satisfaction with the work of their company, as well as opinions on the rational use of natural resources by their company. The survey involved a total of 188 respondents from 11 companies, of which 120 were male (63.8%) male and 68 female (36.2%) female. The T-test shows that respondents differ in terms of the kind of service they provide to clients and whether they meet their expectations. On the basis of the obtained results it is concluded that the linear combination of predictors used is shown to be significant for predicting all the dependent variables we have examined the opinion of the respondents

Analysis of the process crystallization of continuous cast special brass alloys with the acoustic emission method

Analyses of possibilities of monitoring the crystallization process of continuously cast special brass alloys with acoustic emission and for establishing a correlation between the microstructure and the recorded acoustic emission signals. With appropriate selection of parameters for gravitational casting process, continuous casting was performed and samples with a macrostructure typical of continuous casting were obtained. A laboratory plant for the simulation of the continuous casting and for the analysis of the crystallization process with acoustic emission was designed. Different energy levels in samples with different macrostructure, as well as in the defective and non-defective samples, were observed. Two types of sources of signals were defined: the signal during solidification of correct crystallization and macrostructure of continuous casting and acoustic emission signal during solidification of samples in with flaws. To check the obtained results, after completion of the crystallization process, the samples were submitted to external with mechanical loading. The acoustic activity by loading is in accordance with the results of on-line monitoring of the crystallization process with acoustic emission. The results obtained show that it is possible to use the acoustic emission for monitoring the crystallization process by continuous and gravitational casting

Analysis of the financial position of enterprises in privatization in the agricultural sector in Serbia

Privatization as a phase of the transitional process also included agriculture. The most attractive enterprises in agriculture, primarily in the food industry, were privatized in the first wave, while the process of privatization of other less attractive companies was slowed down and implemented mainly by the auction model. The remaining companies waiting for the privatization process are not attractive and there are problems that are expressed through poor financial position and relatively low potential. An exception is made by PKB Corporation, which has a potential and relatively stable market, making this company an acceptable option for investors. The financial position of the companies that are ready for privatization at this moment and which is one of the factors of negative influence on the decision of the investor was analyzed using the Altman Z'-score model, the Kralicek Quick test and the balanced growth model. All tests have shown that the analyzed companies are in a bad financial position and that the future investor will have to invest significant funds in financial consolidation, balancing cash flows and investment in order to ensure adequate development and efficient business

Research of the influence of socio-economic conditions of work on results of business operations of hotel enterprises

The aim of the research is to examine the correlation between the socioeconomic variables of employees (gender, age, level of education, monthly personal income of respondents and monthly personal income of the respondent household, number of members in the household and number of household members who generate income) and opinion of the respondents on the influence of the activities of the presumed on their work and the work of other employees in their hotel, opinions on the satisfaction of dense services, and opinions on the rational use of natural resources by their hotel companies. A total of 205 respondents participated in the survey, out of which 17 questionnaires did not meet the criteria for further analysis, while 188 questionnaires were further analyzed, 120 of them (63.8%) male and 68 respondents (36.2%) female sex. The T-test shows that respondents have different opinions about the services provided to guests and whether they meet their expectations. Namely, men are more satisfied than women in terms of the opinion that guests are satisfied with their work. Also, the obtained results show that more educated men with higher personal monthly income consider that their hotel has a good image of guests, partners and the public, but other groups of respondents. On the basis of the obtained results, it is concluded that the linear combination of predictors used is shown to be significant for predicting all the dependent variables that were examined by the respondents' opinion

Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats

Non-diabetic and alloxan-induced diabetic rats were fed with standard laboratory food enriched with 20% virgincoconut oil for 16 weeks. In non-diabetic animals coconut oil improved insulin sensitivity and ability to controlglycaemia and decreased the serum triglycerides for almost 50% in comparison with controls. Supplementationwith coconut oil caused liver steatosis in both non-diabetic and diabetic animals. However, the severity ofsteatosis was lower in diabetic animals compared to non-diabetic animals. Coconut oil had no effects on hearthistology, ascending and abdominal aorta wall thickening and atherosclerotic plaques development neither innon-diabetic nor in diabetic animals. While alloxan treatment caused Type I diabetes in rats, supplementationwith coconut oil in combination with the alloxan unexpectedly resulted in Type II diabetes. The development ofsevere insulin resistance and deterioration in serum lipid profile implied that the use of coconut oil is contra-indicated in diabetic condition

Antioxidant defense system in the prefrontal cortex of chronically stressed rats treated with lithium

Background This study aimed to investigate the effects of lithium treatment on gene expression and activity of the prefrontal antioxidant enzymes: copper, zinc superoxide dismutase (SOD1), manganes superoxide dismutase (SOD2), catalase (CAT), and glutathione peroxidase (GPx) in animals exposed to chronic restraint stress (CRS). Methods The investigated parameters were quantified using real-time RT-PCR, Western blot analyses, and assays of enzyme activities. Results We found that lithium treatment decreased gene expression of SOD2, as well as the activities of SOD1 and SOD2 in chronically stressed rats to the levels found in unstressed animals. However, lithium treatment in animals exposed to CRS increased prefrontal GPx activity to the levels found in unstressed animals. Conclusions These findings confirm that treatment with lithium induced the modulation of prefrontal antioxidant status in chronically stressed rats. Our results may be very important in biomedical research for understanding the role of lithium in maintaining the stability of prefrontal antioxidant defense system in neuropsychiatric disorders caused by chronic stress

The effect of long-term high-dose coconut oil supplementation on rat sliver and serum lipids

We investigated the effect of long-term high-dose virgin coconut oil (VCO) supplementation on rat liver and serum lipid status. Animals were divided into two groups with 8 of them in each: normally fed (Control group) and the group fed with coconut oil at a concentration of 20% in food (VCO group). The experiment lasted for four months. On the last day of the experiment animals were killed, and blood and liver tissue were collected. In serum we measured the levels of total cholesterol (TC), high-density lipoproteins (HDL), non-HDL lipoproteins, triglycerides (TG), aspartate aminotransferase (9\.ST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). We also measured both liver and serum levels of high mobility group protein B 1 (HMGB 1) and haptoglobin (HP), as ,.vell as the liver level of NF-KB p65/ p-NF-KB p65 transcription factor, together with the histopathology analysis on liver slices and liver Comet assay. The results show that coconut oil do not change serum TC and HDL, but reduces non-HDL and TG levels (10% and 50%, respectively) comparing to control. As a result, atherogenic index of serum (AI) is strongly reduced in VCO group versus control. As for the liver status, results show that coconut supplementation increases AST, ALT and ALP levels in VCO group (50%, 30% and 60%, respectively) comparing to control. This effect is caused by the accumulation of coconut oil fat in liver, as confirmed by the histopathology showing signs of mild nonalcoholic steatohepatitis in VCO group, followed with the increased %of DNA in comet tail. The liver inflammation in VCO group is further demonstrated with the liver HP, HMGBl and p-NF-KB p65 level increase, and increase in nuclear level ofNF­kB p65, but not accompanying serum HP and HMGBl increase. In conclusion, our results show that coconut oil supplementation, despite causing mild and localized steatohepatitis, also lowers serum atherogcnic index, a predictor of cardiovascular risk

The effect of long-term high-dose coconut oil supplementation on rat sliver and serum lipids

We investigated the effect of long-term high-dose virgin coconut oil (VCO) supplementation on rat liver and serum lipid status. Animals were divided into two groups with 8 of them in each: normally fed (Control group) and the group fed with coconut oil at a concentration of 20% in food (VCO group). The experiment lasted for four months. On the last day of the experiment animals were killed, and blood and liver tissue were collected. In serum we measured the levels of total cholesterol (TC), high-density lipoproteins (HDL), non-HDL lipoproteins, triglycerides (TG), aspartate aminotransferase (9\.ST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). We also measured both liver and serum levels of high mobility group protein B 1 (HMGB 1) and haptoglobin (HP), as ,.vell as the liver level of NF-KB p65/ p-NF-KB p65 transcription factor, together with the histopathology analysis on liver slices and liver Comet assay. The results show that coconut oil do not change serum TC and HDL, but reduces non-HDL and TG levels (10% and 50%, respectively) comparing to control. As a result, atherogenic index of serum (AI) is strongly reduced in VCO group versus control. As for the liver status, results show that coconut supplementation increases AST, ALT and ALP levels in VCO group (50%, 30% and 60%, respectively) comparing to control. This effect is caused by the accumulation of coconut oil fat in liver, as confirmed by the histopathology showing signs of mild nonalcoholic steatohepatitis in VCO group, followed with the increased %of DNA in comet tail. The liver inflammation in VCO group is further demonstrated with the liver HP, HMGBl and p-NF-KB p65 level increase, and increase in nuclear level ofNF­kB p65, but not accompanying serum HP and HMGBl increase. In conclusion, our results show that coconut oil supplementation, despite causing mild and localized steatohepatitis, also lowers serum atherogcnic index, a predictor of cardiovascular risk