Glucose tolerance tests (GTT) showed that ksr1 -/- mice have a slight, but significant, decrease in glucose tolerance at early time points. This is in contrast to mark2 -/- mice, which have increased glucose tolerance (Fig. 4B and ). We found that deletion ofKSR1 in mark2 -/- mice does not revert the enhanced glucose tolerance observed in mark2 -/- mice. Instead, DKO mice have glucose tolerance similar to mark2 -/- mice. As glucose tolerance is a composite of the effects ofglucose on insulin secretion and the responsiveness of peripheral tissues for insulin-stimulated glucose uptake, the results could reflect a combination of increased insulin Figure 1. MARK2 interacts with KSR1. A. KSR1-FLAG, C-TAK1-HA, MARK2-HA and their respective vectors were transfected in combination in 293T cells. Thirty-six hours after transfection, cells were lysed and immunoprecipitated with FLAG- and HA-specific antibodies. Proteins were detected on a western blot using antibodies to each epitope tag. B. Schematic ofKSR1 constructs used. C. KSR1-FLAG WT or mutants were co-transfected with C-TAK1-HA, MARK2-HA, or empty vectors and cells were lysed and immunoprecipitations performed as in A. IP: immunoprecipitation, WCL: Whole Cell Lysate. * non-specific band.
As an animal moves through the fed, fasting and fasted states, its body switches to different types of metabolic fuels to stabilize blood glucose concentration. This transition is controlled in large part by the blood levels of insulin and glucagon, both of which are generated in a reciprocal manner by the pancreas in response to changing blood glucose levels. Insulin and glucagon are mutually antagonistic with respect to many aspects of intermediary metabolism and their effects on bioenergetics [25,34]. Insulin is a key regulator for carbohydrate and fat metabolism in the body. It enhances blood glucose uptake to form triglycerides and glycogen and suppresses pathways such as gluconeogensis and glycogenolysis . Glucagon, on the other hand, is secreted from the pancreas when blood glucose concentration is low. It inhibits glycolysis and stimulates hepatic glycogenolysis and gluconeogenesis in liver by increasing the concentration of cAMP . The elevated level of cAMP in turn activates a cascade of enzymes in the glycogen control circuitry that enhance the degradation of glycogen molecules . Insulin and glucagon, working in a reciprocal fashion, in conjunction with other hormonal regulators, such as leptin and epinephrine, maintain glucosehomeostasis in biological systems. Our physiological model also incorporates aspects of the Cori cycle, where lactate from muscle and erythrocytes is carried to the liver and converted to glucose for reuse by these tissues.
cell lines was only 14%, suggesting some degree of similarity at O-glycoproteome level. Moreover, the glycoproteome of all cell lines share similar biological and molecular functions, while having similar intracellular distribution (Figure 2). According to a STRING analysis, these glycoproteins show a significant degree of interaction, suggesting a high level of synergism towards common biological functions (Figure 3). Moreover, GO analysis suggests that many of these glycoproteins interact to drive cellular motion (Figures 3 and 4), as previously highlighted by our glycoproteomics studies in BC cell models (74) and tumours (67). Finally, GO term analysis suggests that these glycoproteins may contribute to sort and carry molecular information across different subcellular compartments. This hypothesis is further reinforced by the fact that all the identified glycoproteins may be found in more than one subcellular location, as highlighted by Figure 5. Supporting these observations, many intracellular proteins have been found at the cell membrane in cancer cells, constituting important sources of highly specific cancer biomarkers (174-177). In addition, the main represented functions and processes of these glycoproteins include substrate-specific transport and ion channel activities, suggesting key participation in cellular homeostasis, as well as in cytoskeletal protein binding, denoting a potential role in defining cellular shape. In turn, the main intracellular pathways in which these glycoproteins are prevalent include the ABC transporters network, several players in the regulationof the cytoskeleton, and proteoglycan-mediated signaling pathways (Figure 3). The majority of biological processes highlighted in the cytoscape analysis include cell-cell and cell-extracellular matrix adhesion mainly mediated by Integrin beta-1 (ITGB1), C-terminal focal adhesion targeting (FAT), and vinculin (VCL). Moreover, immunological processes such as Interleukin-2 (IL-2) secretion and activation of CD8 + αβ T cells are also mediated by hub
Figure 2.1 illustrates two different methods used to assess glucose tolerance. Figure 2.1A shows the curve of an intra-enteric glucose tolerance test (IEGGT) obtained by measuring blood glucose levels at several time points. This test is performed with animals anesthetized and consists in the administration of a bolus ofglucose directly in the gut. Blood glucose levels rise reaching a maximum point normally between 20 and 30 minutes after glucose infusion. Glucose levels start to decrease after they reach their maximum, however, blood glucose values do not normally return to the baseline value as it is evident by the curve of the figure 2.1A. Maintenance of high glucose levels during 120 minutes of the test may be explained due to different factors. Anesthesia reduces intestinal motility which leads to a delay in glucose absorption. Moreover, once glucose is given in the gut there is a lack in the signals given by the sense of a meal in the mouth that contribute to a faster disappearance ofglucose in the bloodstream.
The above procedure would easily enable one systematically assign ranks to sampled observations drawn from a given population whether or not there are tied observations and simultaneously estimate the sum and mean of these ranks. Similarly, the method enables one to easily obtain more efficient estimates of the sum of squares and cross products of ranks of sample observations whether or not some or all of the observations are tied in values and hence assigned mean ranks. With these results, one may now proceed to estimate some ties adjusted statistics. For example, one may estimate ties adjusted Spearman rank correlation coefficient between pairs of observations drawn from populations X 1 and X 2 .
Stata 7 statistical software was used in the data analy- sis. Absolute and relative risk factor frequencies were calculated, in addition to their distribution according to age group. The data were expressed as means, confi- dence intervals or percentages. A 5% significance level was set. Categorical variables were compared using Pearson’s chi-square test. Continuous variables were compared using Student’s t-test or Anova. All of these statistic tests were bivariate and to control for effect of the study design (cluster sampling) it was used various “svy” Stata commands, creating clusters representing each one of the micro-regions in the state of RS. Logis- tic regression models, controlled for the effect of the study design, were applied to control for the effects of age and BMI on the associations found between the risk factors and the degree ofglucosehomeostasis
and 10% w/v) applied for 15 minutes to conspecifics elicited increase in swimming activity and in the area visited by the fish inside the tank. However, exposure to the epithelial alarm cue did not evoke any stress response: plasma osmolality, ions (sodi- um, chloride, magnesium, and potassium), glucoseand cortisol remained unchanged. In conclusion, the conspecific alarm cue of the jundiá induces behavioral responses but not an acute stress response upon short-term exposure, compatible with its role in fostering physical integrity without representing major stress activation. Considering that in the natural environment such stimuli must quickly disappear due to dilution and that rapid protection responses may be necessary upon the possibility of an approaching predator, a faster mechanism to assure survival may come into play, such as sympathetic nervous system activation. Comunicação química é amplamente utilizada por animais que vivem em ambiente aquático, onde sinais visuais e auditivos nem sempre são facilmente identificados. Os Ostariophysi são conhecidos por apresentarem células club na epiderme, as quais produzem e estocam substância de alarme que são liberadas para o ambiente quando a pele é lesionada. As respostas dos peixes a substância de alarme variam entre exploração ativa por refúgios até a parada completa de atividade locomotora. Neste estu- do, grande número de células club binucleadas (densidade média de 11 células/µm2) foram histologicamente observadas na epiderme do jundiá, Rhamdia quelen. Peixes expostos a extrato de pele de conspecíficos (2, 5, e 10% peso/vol) por 15 minutos apresentaram aumento da atividade locomotora e da área de dispersão. No entanto, essa exposição não promoveu nenhuma resposta de estresse - osmolalidade plasmática, íons (sódio, cloreto, magnésio e potássio), glicose e cortisol não sofreram alteração. Concluímos que a exposição aguda a extrato de pele de conspecíficos promovem respostas comportamentais de fuga, que essa espécie apresenta grande concentração de células club, as quais devem estar envolvidas nessas respostas e que a exposição aguda ao estímulo não promoveu respostas bioquímicas indicativas de estresse. Considerando que no ambiente natural tais estímulos devem desaparecer rapidamente dados a diluição do meio e que respostas rápidas de proteção devem ser desencadeadas frente à possibilidade de presença de predador, vias rápidas de suporte a essas respostas, como sistema nervoso simpático, por exemplo, devem estar envolvidos.
The plant may perceive and respond to microbial invasion by sending the proper signals thus orchestrating a complex network of interactions; and most land plants can enter into symbioses with mycorrhizal fungi (Smith and read, 2008). A number of features including fungal infection of the host plant, transcriptional activation of a subset of plant genes and formation of an intracellular interface where nutrient exchange occurs being the direct effect on host ionome (Stracke et al., 2002; Bidartondo et al., 2002; Genre et al., 2008; Bonfante and Genre, 2010). Actually, genetic and molecular analyses in the model legumes Medicago truncatula and Lotus japonicus identified multiple genes that are required for mycorrhizal symbiosis (novero et al., 2002; Bais et al., 2004; Harrison, 2005; maeda et al., 2006; Kiriachek et al., 2009). merging information from transcriptomics, metabolomics and proteomics into consistent models, it will be possible to describe and predict the behaviour of biological systems, for example with respect to endogenous or environmental changes (Holger and rainer, 2006). ionomics of symbiotic interactions has the ability to capture information about the functional state of a host under different conditions, driven by genetic and developmental differences induced by mycorrhizal fungus (williams and Salt, 2009).
One of the limitations to this investigation is that we did not register psychophysiological correlates of infant emotion regulation during the Shape Sorter Task. Therefore, the validity of the three proposed styles of emotion regulation remains an open issue. Analyzing relations to future child adaptive outcomes would also contribute to this end. Additionally, we did not control for the mother’s behavior in the Shape Sorter Task, which may have conditioned the scoring of this measure. Nevertheless, Diener et al. (2002) demonstrated that emotion regulation skills seem to become organized into patterns or styles starting as early as the end of the first year of life. This suggests that the infant is considerably influencing the final score on the Shape Sorter Task. If this is not the case, however, and it is the mother’s behavior that is greatly influencing the infant’s emotional regulation style, there is a theoretical expectation that the infant will internalize these patterns and emotional regulation strategies (Sroufe, 1996). Therefore, the interaction during the Shape Sorter Task may be considered a reflection of the way the dyad has been resolving emotionally activating situations. Based on this framework, the results will be an index to the child’s style of emotion regulation that he/she will use
In this study, we chose to use the oral glucose tolerance test (OGTT) to measure insulin sensitivity. Even though the glucose clamp technique  is widely accepted as the standard reference for directly determining metabolic insulin sensitivity in humans, this method requires anesthesia, which is known to influence glycemia even in a fasting state. Additionally, OGTT reflects the efficiency with which the organism disposes ofglucose after an oral glucose load. Thus, it provides useful information about glucose tolerance, and the OGTT data allow for the assessment of one of the surrogate validated indices of insulin sensitivity, the homeo- stasis model assessment (HOMA-IR index). In addition, the grey mouse lemur does not allow for large blood volume sampling because it has a low circulating blood volume. Thus, OGTT was the most suitable method to evaluate the glucose tolerance and insulin resistance of this primate model. Markers of insulin sensitivity were assessed through OGTT and the HOMA-IR index in two different groups of mouse lemurs: one group after 21 months of chronic CR or RSV treatment and another group after 33 months of chronic CR or RSV treatment. The resting metabolic rate (RMR) was also assessed, as it is a relevant component of daily energy expenditure estimation and a widely used predictive factor of body mass gain in human studies . RMR has also been associated with metabolic syndrome in humans . We were therefore interested in evaluating the relationships between this parameter and markers of insulin sensitivity.
A third, and perhaps most important, implication of this work is that a normal function of activated macrophages is to suppress the BMP pathway in a paracrine manner in their microenvironment. In the short term, this has effects beneficial to wound healing: it decreases endothelial cell-cell junctions  to improve macro- phage invasion , and induces a metabolic shift , increased proliferation  and migration  to support wound healing. In normal injury, this is terminated by negative feedback signaling arising from both within the macrophage (eg via Smad6, Fig. 5E) and from the nearby vascular mural cells [11,22]. Moreover, suppression of Smad6 not only acts as negative feedback, allowing reactivation of the BMP pathway, but also may directly disinhibit NF-kB activation . Smad6 inhibition thus may be part of a short term activation and long term inhibition program. In PAH, either the presence of a BMPR2 mutation or, potentially, other genetic or environmental factors, results in continued suppression of the BMP pathway and a persistent inflammatory state.
We would like to thank Prof. Ana L. P. Miranda and Rogerio A. Panizzutti for the helpful support. This research was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ). The funding agencies had no role in the study design, data collection, data analysis, decision to publish or preparation of the manuscript. All authors have contributed to the conception and design or analysis and interpretation of the data, drafting the article, revising it critically for important intellectual content and have given their final approval of the version to be published.
in this study. Type 2 diabetes mellitus was observed in 11 patients (33.3%), andglucose intolerance was observed in 4 patients (12.1%). Mean plasma fasting glucose levels were 109.77 ± 44.19 mg/dl (75-320) in the preoperative period. All Silastic® ring sleeve gastrectomy procedures were performed by the same surgical team using the same anesthetic technique. The patients were monitored for at least 12 months after surgery.
Some of the most successful neuroregu- lators experimentally used so far in crusta- ceans are serotonin (5-hydroxytryptamine, 5-HT) and some of its related drugs or modu- lators, like fenfluramine (a serotonin releaser) and fluoxetine (a serotonin potentiator) (7). As part of our research directed at the understanding of hormone release regula- tion in crustaceans, in the present investiga- tion we studied the effect of serotonin and fluoxetine on blood glucose levels in the decapods Chasmagnathus granulata and Or- conectes limosus.
To perform the test a load source (ZD 10/90, no. 46/79) has been used. The test was conducted in accordance with STN 42 0310. As a result of this test, the variable Rm ( tensile strength ) and A6 (elongation) have been obtained. The values (Rm, A6) are arithmetical averages of values obtained from 3 samples poured under identical conditions, to eliminate effect of random events and to ensure that the measurements was objective. From this values the graphs was created (figure 2 – 3), on which is represented relation of tensile strength and elongation from amount of re-melts and filter attendance.
The mechanism of action of GLP1 during fasting essentially involves the secretion ofglucose-dependent insulin and inhibition of glucagon. Recent studies have demonstrated, however, that its action in the postprandial state occurs through deceleration of gastric emptying, leading to reduced entry ofglucose in circulation. (26) The concomitant use of prokinetic agents,
Figure 1). Therefore, we prepared duplicate samples for RNA-seq at 3 h, 6 h, 9 h, and 24 h after glucose deprivation. The control samples with 25 mM glucose were prepared in triplicate. RNA-seq analysis was performed using the ELAND_RNA of CASAVA software and hg19 human genome database as a reference. This analysis resulted in alignments with 14202,16218 genes from each sample, out of a total of 21407 annotated genes in the database (Table S2). Gene expression was calculated for every gene and given a value corresponding to ‘read per kilobase of exon model’ (RPKM), which is the number of reads aligning to a gene, divided by the length of the gene and the total number of reads . We selected three samples (I, II and III) derived from cells incubated in 25 mM glucose medium. Four samples (0 mM Glucose 6 h-I, II, Glucose 9 h-I and II) were selected as glucose- deprivation samples. We analyzed genes that were differentially expressed in cells incubated in medium lacking glucose (0 mM glucose) and medium containing 25 mM glucose using the ‘Find Significant Pathway’ analysis software package (Avadis NGS software, Table 1). Table 1 shows the most significantly affected pathways i.e., 9 up- and 11 down-regulated pathways (p,0.0001). Figure 1. The glycosylation induced under glucose deprivation was not regulated by OGT and O -GlcNAcase. A, An immunoblot showing CTD110.6 antibody and anti-CD98HC antibody reaction over the time course during incubation of T24 cells in glucose-deprived medium (0 mM glucose). B, The effects of tunicamycin treatment on the expression of proteins that reacted with CTD110.6 and anti-CD98HC antibodies under glucose deprivation. An anti-a-tubulin antibody was used as an internal control. Note that N-GlcNAc 2 -modified glycoproteins are undetectable after
In addition to classic functions of facilitating hepatobiliary secretion and intestinal absorption of lipophilic nutrients, bile acids (BA) are also endocrine factors and regulate glucoseand lipid metabolism. Recent data indicate that antiobesity bariatric procedures e.g. Roux-en-Y gastric bypass surgery (RYGB), which also remit diabetes, increase plasma BAs in hu- mans, leading to the hypothesis that BAs may play a role in diabetes resolution following surgery. To investigate the effect of RYGB on BA physiology and its relationship with glu- cose homeostasis, we undertook RYGB and SHAM surgery in Zucker diabetic fatty (ZDF) and normoglycemic Sprague Dawley (SD) rats and measured plasma and fecal BA levels, as well as plasma glucose, insulin, Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY), 2 days before and 3, 7, 14 and 28 days after surgery. RYGB decreased body weight and in- creased plasma GLP-1 in both SD and ZDF rats while decreasing plasma insulin and glu- cose in ZDF rats starting from the first week. Compared to SHAM groups, both SD-RYGB and ZDF-RYGB groups started to have increases in plasma total BAs in the second week, which might not contribute to early post-surgery metabolic changes. While there was no sig- nificant difference in fecal BA excretion between SD-RYGB and SD-SHAM groups, the ZDF-RYGB group had a transient 4.2-fold increase (P<0.001) in 24-hour fecal BA excretion on post-operative day 3 compared to ZDF-SHAM, which paralleled a significant increase in plasma PYY. Ratios of plasma and fecal cholic acid/chenodeoxycholic acid derived BAs were decreased in RYGB groups. In addition, tissue mRNA expression analysis suggested early intestinal BA reabsorption and potentially reduced hepatic cholic acid production in RYGB groups. In summary, we present novel data on RYGB-mediated changes in BA me- tabolism to further understand the role of BAs in RYGB-induced metabolic effects
Unlike the prefrontal cortex, the hypothalamus has been largely studied with respect to the mechanisms ofglucose interaction with neurons. In this region, glucose-inhibited andglucose-excited neurons have been characterized, both types displaying abnormal response to glucose varia- tions in obese rats. Particularly in the medial hypothal- amus, increment ofglucose levels has been shown to decrease firing rate of NPY-expressing glucose-inhibited neurons while increasing that of POMC-expressing neu- rons, thus leading to feeding inhibition [13,50-52]. Thus, failure of i.c.v. glucose to consistently inhibit feeding in the fish-oil group could rely on impaired glucose action on these neurons. This notion is compatible with the demonstration that glucose transporter 2 null mice be- came hyperphagic, had disrupted hypothalamic neuropep- tides expression, and failed to respond with hypophagia to either i.c.v. or intraperitoneal glucose .
To test these hypotheses, we developed a virtual foraging task. In each trial, human partici- pants chose between two “foraging environments” with different possible “energy” gains and associated probabilities, in which they would forage for up to three consecutive “days” (see Fig 1A for illustration). At the time of choice, an energy bar depicted participants’ current in- ternal state. Participants were instructed that on each foraging day, they would lose one energy point, and gain energy according to the statistics of the chosen environment. Successive days in the task required the integration of risks from multiple foraging attempts. For each trial, partic- ipants made a single decision between the two foraging environments for the indicated number of days. Losing all energy points on any day in a given foraging period was framed as “starva- tion” but was not explicitly punished. Each trial was independent. We did not give feedback on choice outcomes of their choices or intermediate states of the foraging sequence. At the end of the experiment, participants were rewarded for the endpoint foraging outcome of two random- ly selected trials. Starvation meant that participants did not win anything from the trial. We hy- pothesized that participants would compute the probability of starvation for the foraging environments and base their decisions on this metric.