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High glucose and fructose intake have been proven to display pro-inflammatory roles during the progression of inflammatory diseases. However, mannose has been shown to be a special type of hexose that has immune regulatory functions. In this review, we trace the discovery process of the regulatory functions of mannose and summarize some past and recent studies showing the therapeutic functions of mannose in inflammatory diseases. We conclude that treatment with mannose can suppress inflammation by inducing regulatory T cells, suppressing effector T cells and inflammatory macrophages, and increasing anti-inflammatory gut microbiome. By summarizing all the important findings, we highlight that mannose treatment is a safe and promising novel strategy to suppress inflammatory diseases, including autoimmune disease and allergic disease.

Over-express galactokinase (Galk1) in tissue plasminogen activator (tPA) producing CHO cells as a potential strategy to improve cell growth and product synthesis. tPA producing CHO cells were transfected with the galactokinase (Galk1) gene. CHO-Galk1 cells showed a 39% increase of the specific growth rate in galactose. Moreover, clones were able to use this hexose as their main carbon source to sustain growth contrary to their parental cell line. Metabolic Flux Analysis revealed that the CHO-Galk1 selected clone shows an active metabolism towards biomass and product synthesis, characterized by higher fluxes in the TCA cycle, which is consistent with increased cellular densities and final product concentration. This cellular engineering strategy, where modifications of key points of alternative carbon sources metabolism lead to an improved metabolism of these sugars, is a starting point towards the generation of new cell lines with reduced lactate synthesis and increased cell growth and productivity.

The effects of birth weight (BiW; low BiW [LBW] vs. high BiW [HBW]) and estimated breeding value (EBV) for protein deposition (low EBV [LBV] vs. high EBV [HBV]) on N retention, N efficiency, and concentrations of metabolites in plasma and urine related to N efficiency in growing pigs were studied. At an age of 14 wk, 10 LBW–LBV (BiW: 1.07 ± 0.09 [SD] kg; EBV: −2.52 ± 3.97 g/d, compared with an average crossbred pig with a protein deposition of 165 g/d), 10 LBW–HBV (BiW: 1.02 ± 0.13 kg; EBV: 10.47 ± 4.26 g/d), 10 HBW–LBV (BiW: 1.80 ± 0.13 kg; EBV: −2.15 ± 2.28 g/d), and 10 HBW–HBV (BiW: 1.80 ± 0.15 kg; EBV: 11.18 ± 3.68 g/d) male growing pigs were allotted to the experiment. The pigs were individually housed in metabolism cages and were subjected to an N balance study in two sequential periods of 5 d, after an 11-d dietary adaptation period. Pigs were assigned to a protein adequate (A) or protein restricted (R, 70% of A) regime in a change-over design. Pigs were fed 2.8 times the energy requirements for maintenance. Nontargeted metabolomics analyses were performed in urine and blood plasma samples. The N retention (in g/d) was higher in the HBW than in the LBW pigs (P < 0.001). The N retention (in g/[kg metabolic body weight (BW0.75) · d]) and N efficiency, however, were not affected by the BiW of the pigs. The N retention (P = 0.04) and N efficiency (P = 0.04) were higher in HBV than in LVB pigs on the A regime but were not affected by EBV in pigs on the R regime. Restricting the dietary protein supply with 30% decreased the N retention (P < 0.001) but increased the N efficiency (P = 0.003). Nontargeted metabolomics showed that a hexose, free amino acids (AA), and lysophosphatidylcholines were the most important metabolites in plasma for the discrimination between HBV and LBV pigs, whereas metabolites of microbial origin contributed to the discrimination between HBV and LBV pigs in urine. This study shows that BiW does not affect N efficiency in the later life of pigs. Nitrogen efficiency and N retention were higher in HBV than in LBV pigs on the A regime but similar in HBV and LBV pigs on the R regime. In precision feeding concepts aiming to further optimize protein and AA efficiency in pigs, the variation in EBV for protein deposition of pigs should be considered as a factor determining N retention, growth performance, and N efficiency.

We hypothesized that maternal nutrition during the first 50 d of gestation would influence the abundance of hexose transporters, SLC2A1, SLC2A3, and SLC2A5, and cationic amino acid transporters, SLC7A1 and SLC7A2, in heifer uteroplacental tissues. Angus-cross heifers (n = 43) were estrus synchronized, bred via artificial insemination, and assigned at breeding to 1 of 2 dietary intake groups (CON = 100% of requirements to achieve 0.45 kg/d of BW gain or RES = 60% of CON intake) and ovariohysterectomized on day 16, 34, or 50 of gestation (n = 6 to 9/d) in a completely randomized design with a 2 × 3 factorial arrangement of treatments. Uterine cross-sections were collected from the horn ipsilateral to the corpus luteum, fixed in 10% neutral buffered formalin, sectioned at 5 µm, and stained via immunofluorescence for transporters. For each image, areas of fetal membrane (FM; chorioallantois), luminal epithelium (ENDO), superficial glands (SG), deep glands (DG), and myometrium (MYO) were analyzed separately for relative intensity of fluorescence as an indicator of transporter abundance. Analysis of FM was only conducted for days 34 and 50. No transporters in target areas were influenced by a day × treatment interaction (P ≥ 0.06). In ENDO, all transporters were differentially abundant from days 16 to 50 of gestation (P ≤ 0.04), and SLC7A2 was greater (P = 0.05) for RES vs. CON. In SG, SLC7A1 and SLC7A2 were greater (P ≤ 0.04) at day 34 vs. day 16. In DG, SLC2A3 and SLC7A1 were greater (P ≤ 0.05) for CON vs. RES heifers; furthermore, SLC7A1 was greater (P < 0.01) at day 50 vs. days 16 and 34 of gestation. In MYO, SLC7A1 was greater (P < 0.01) for CON vs. RES and was greater (P = 0.02) at days 34 and 50 vs. day 16. There were no differences in FM (P ≥ 0.06). Analysis of all uterine tissues at day 16 determined that SLC2A1, SLC2A3, and SLC7A2 were all differentially abundant across uterine tissue type (P < 0.01), and SLC7A1 was greater (P = 0.02) for CON vs. RES. Analysis of all uteroplacental tissues at days 34 and 50 demonstrated that all transporters differed (P < 0.01) across uteroplacental tissues, and SLC7A1 was greater (P < 0.01) for CON vs. RES. These data are interpreted to imply that transporters are differentially affected by day of gestation, and that hexose and cationic amino acid transporters are differentially abundant across utero-placental tissue types, and that SLC7A1 is responsive to maternal nutritional treatment.

Objective Glucose is the major energy substrate of the brain and crucial for normal brain function. In diabetes, the brain is subject to episodes of hypo- and hyperglycemia resulting in acute outcomes ranging from confusion to seizures, while chronic metabolic dysregulation puts patients at increased risk for depression and Alzheimer's disease. In the present study, we aimed to determine how glucose is metabolized in different regions of the brain using imaging mass spectrometry (IMS). Methods To examine the relative abundance of glucose and other metabolites in the brain, mouse brain sections were subjected to imaging mass spectrometry at a resolution of 100 μm. This was correlated with immunohistochemistry, qPCR, western blotting and enzyme assays of dissected brain regions to determine the relative contributions of the glycolytic and pentose phosphate pathways to regional glucose metabolism. Results In brain, there are significant regional differences in glucose metabolism, with low levels of hexose bisphosphate (a glycolytic intermediate) and high levels of the pentose phosphate pathway (PPP) enzyme glucose-6-phosphate dehydrogenase (G6PD) and PPP metabolite hexose phosphate in thalamus compared to cortex. The ratio of ATP to ADP is significantly higher in white matter tracts, such as corpus callosum, compared to less myelinated areas. While the brain is able to maintain normal ratios of hexose phosphate, hexose bisphosphate, ATP, and ADP during fasting, fasting causes a large increase in cortical and hippocampal lactate. Conclusion These data demonstrate the importance of direct measurement of metabolic intermediates to determine regional differences in brain glucose metabolism and illustrate the strength of imaging mass spectrometry for investigating the impact of changing metabolic states on brain function at a regional level with high resolution., Highlights • Utilization of glucose for glycolysis or the pentose phosphate pathway (PPP) is region-specific. • IMS allows simultaneous measurement of glucose metabolites across brain regions. • PPP is high in thalamus, while glycolysis predominates in cortex and amygdala. • Fasting induces changes in lactate distribution but not glucose metabolites or ATP.

Mice subjected to cold or caloric deprivation can reduce body temperature and metabolic rate and enter a state of torpor. Here we show that administration of pyruvate, an energy-rich metabolic intermediate, can induce torpor in mice with diet-induced or genetic obesity. This is associated with marked hypothermia, decreased activity, and decreased metabolic rate. The drop in body temperature correlates with the degree of obesity and is blunted by housing mice at thermoneutrality. Induction of torpor by pyruvate in obese mice relies on adenosine signaling and is accompanied by changes in brain levels of hexose bisphosphate and GABA as detected by mass spectroscopy-based imaging. Pyruvate does not induce torpor in lean mice but results in the activation of brown adipose tissue (BAT) with an increase in the level of uncoupling protein-1 (UCP1). Denervation of BAT in lean mice blocks this increase in UCP1 and allows the pyruvate-induced torpor phenotype. Thus, pyruvate administration induces torpor in obese mice by pathways involving adenosine and GABA signaling and a failure of normal activation of BAT.

Context: Olive oil is the major source of tyrosol which is a natural phenolic antioxidant. Olive oil constitutes a major component of the Mediterranean diet that is linked to a reduced incidence of chronic diseases. Objective: This study evaluates the effects of tyrosol on altered glycoprotein components in streptozotocin-induced diabetic rats. Materials and methods: Diabetes mellitus was induced in male Wistar rats by streptozotocin (40 mg/kg body weight). These rats were administered tyrosol (20 mg/kg body weight) and glibenclamide (600 μg/kg body weight) orally daily for 45 days. Plasma glucose, plasma insulin, glycoprotein components such as hexose, hexosamine, sialic acid and fucose in the plasma, liver and kidney, and histopathogy of tissues were analyzed. Results: Diabetic rats revealed significant (p

A novel, phosphate-binding exobiopolymer (EBP) produced by Acinetobacter haemolyticus MG606 was characterized and its biocompatibility evaluated in RAW 264.7 cells and in mice. EBP was identified as a 50 kDa heteropolysaccharide composed of pentose and hexose sugars. EBP exhibited cytotoxicity, stimulation of free radical production and loss of mitochondrial and lysosomal integrity in RAW 264.7 cells at 500 μg/mL concentration while lower concentrations exhibited no significant (p > 0.05) effect on these parameters. EBP exhibited dose-dependent mortality, body weight reduction, hypothermia and clinical signs of toxicity in mice following intraperitoneal administration. The LD50 of EBP was determined to be 92.31 mg/kg. Overall, the results of our study suggest that composition of EBP produced by A. haemolyticus MG606 is distinct from EBP produced by other Acinetobacter spp. The high biocompatibility supports application of EBP as a safe biosorbent for phosphate remediation.

Background l-Fucose (Fuc), a six-deoxy hexose monosaccharide, is present endogenously in humans and animals and has a wide range of biological functions. In the present study, we aimed to examine the effect of Fuc on obesity and hepatic steatosis in mice fed a high-fat diet (HFD). Methods C57BL/6 mice were fed a normal chow (NC) or HFD for 18 weeks to induce obesity and fatty liver. Fuc was administered intragastrically from the 8th week to the end of the experiment (18 weeks). Results Metagenomic analysis showed that HFD altered the genomic profile of gut microbiota in the mice; specifically, expression of alpha-l-fucosidase, the gene responsible for Fuc generation, was markedly reduced in the HFD group compared with that in the NC group. Fuc treatment decreased body weight gain, fat accumulation, and hepatic triglyceride elevation in HFD-fed mice. In addition, Fuc decreased the levels of endotoxin-producing bacteria of the Desulfovibrionaceae family and restored HFD-induced enteric dysbiosis at both compositional and functional levels. Conclusion Our findings suggest that Fuc might be a novel strategy to treat HFD-induced obesity and fatty liver.

Glycolysis, mitochondrial substrate oxidation, and the pentose phosphate pathway (PPP) are critical for neuronal bioenergetics and oxidation-reduction homeostasis, but quantitating their fluxes remains challenging, especially when processes such as hexose phosphate (i.e., glucose/fructose-6-phosphate) recycling in the PPP are considered. A hexose phosphate recycling model was developed which exploited the rates of glucose consumption, lactate production, and mitochondrial respiration to infer fluxes through the major glucose consuming pathways of adherent cerebellar granule neurons by replicating [(13)C]lactate labeling from metabolism of [1,2-(13)C2]glucose. Flux calculations were predicated on a steady-state system with reactions having known stoichiometries and carbon atom transitions. Non-oxidative PPP activity and consequent hexose phosphate recycling, as well as pyruvate production by cytoplasmic malic enzyme, were optimized by the model and found to account for 28 ± 2% and 7.7 ± 0.2% of hexose phosphate and pyruvate labeling, respectively. From the resulting fluxes, 52 ± 6% of glucose was metabolized by glycolysis, compared to 19 ± 2% by the combined oxidative/non-oxidative pentose cycle that allows for hexose phosphate recycling, and 29 ± 8% by the combined oxidative PPP/de novo nucleotide synthesis reactions. By extension, 62 ± 6% of glucose was converted to pyruvate, the metabolism of which resulted in 16 ± 1% of glucose oxidized by mitochondria and 46 ± 6% exported as lactate. The results indicate a surprisingly high proportion of glucose utilized by the pentose cycle and the reactions synthesizing nucleotides, and exported as lactate. While the in vitro conditions to which the neurons were exposed (high glucose, no lactate or other exogenous substrates) limit extrapolating these results to the in vivo state, the approach provides a means of assessing a number of metabolic fluxes within the context of hexose phosphate recycling in the PPP from a minimal set of measurements.

(2S,3R,4R,5S,6R)-2-Aryl-5,5-difluoro-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4-diols and (2S,3R,4R,5S,6R)-2-aryl-5-fluoro-5-methyl-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4-diols were discovered as dual inhibitors of sodium glucose co-transporter proteins (e.g. SGLT1 and SGLT2) through rational drug design, efficient synthesis, and in vitro and in vivo evaluation. Compound 6g demonstrated potent dual inhibitory activities (IC50 = 96 nM for SGLT1 and IC50 = 1.3 nM for SGLT2). It showed robust inhibition of blood glucose excursion in an oral glucose tolerance test (OGTT) in Sprague Dawley (SD) rats when dosed at both 1 mg/kg and 10 mg/kg orally. It also demonstrated postprandial glucose control in db/db mice when dosed orally at 10 mg/kg.

Over recent years, the presence of the sweet taste receptor TIR3 in rodent and human insulin-producing pancreatic islet β-cells was documented. The activation of this receptor by sweet-tasting sucralose mimics several biochemical and functional effects of d-glucose in the β-cells. The present study extends this analogy to the bioelectrical response of β-cells. In this respect, sucralose was inefficient in the absence of d-glucose, but induced on occasion electrical activity in mouse β-cells exposed to low non-stimulatory concentrations of the hexose and potentiated, in a concentration-related manner, the response to stimulatory concentrations of d-glucose. These data indicate that sucralose, acting as an agonist of the TIR3 receptor, exerts an excitatory effect upon pancreatic β-cell bioelectrical activity.

While effects of (a)biotic stress events in the phyllosphere have been studied intensively, possible influences of stress on the arbuscular mycorrhizal hyphosphere has scarcely been investigated. We hypothesised that stress challenge in the phyllosphere could alter primary metabolite profiles of the hyphosphere - the mycelial network connecting plants. Donor plants, connected to receiver plants by mycelial networks, were aphid-challenged during 84 h. Primary metabolite profiles in the hyphosphere were investigated. Gene-expression of plant defence gene PR1 was measured in one of the receiver plants during the challenge. Hexose levels in the hyphosphere increased when donor plants were aphid-challenged. This change in metabolic profile was influenced by leaf sampling from receiver plant. PR1 expression increased in donor plants 48 h after challenge, and consequently 60 h after, in receiver plants. We conclude that aphid infestation of donor plants modified primary carbon metabolism in the hyphosphere. Plant defence response in receiver plants, occurred 12 h after detection of response in the aphid-challenged donor plants. While this work is the first to reveal primary metabolic profiles of the AM hyphosphere, more work is needed to elucidate the possible role of transient changes of hexose metabolism in stress response and signalling processes in the hyphosphere of connected plants.

Besides the liver, which has always been considered the major source of endogenous glucose production in all post-absorptive situations, kidneys and intestines can also produce glucose in blood, particularly during fasting and under protein feeding. However, observations gained in different experimental animals have given ambiguous results concerning the presence of the glucose-6-phosphatase system in the small intestine. The aim of this study was to better define the species-related differences of this putative gluconeogenic organ in glucose homeostasis. The components of the glucose-6-phosphatase system (i.e., glucose-6-phosphate transporter and glucose-6-phosphatase itself) were analyzed in homogenates or microsomal fractions prepared from the small intestine mucosae and liver of rats, guinea pigs, and humans. Protein and mRNA levels, as well as glucose-6-phosphatase activities, were detected. The results showed that the glucose-6-phosphatase system is poorly represented in the small intestine of rats, on the other hand, significant expressions of glucose-6-phosphate transporter and of the glucose-6-phosphatase were found in the small intestine of guinea pigs and homo sapiens. The activity of the recently described fructose-6-phosphate transporter&ndash, intraluminal hexose isomerase pathway was also present in intestinal microsomes from these two species. The results demonstrate that the gluconeogenic role of the small intestine is highly species-specific and presumably dependent on feeding behavior (e.g., fructose consumption) and the actual state of metabolism.

Elevated growth in breast cancer (BC) activates hypoxia-inducible factor (HIF1α) and downstream, facilitative glucose transporter 1 (GLUT1), which can be visualized with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG). GLUT5 (fructose) and GLUT2 (glucose/fructose) might provide alternative targets for BC imaging as to why effects of hypoxia on GLUT1/2/5 levels and function were examined in human BC models. GLUT1/2/5 and HIF1α mRNA was analyzed in BC patient biopsies. In MCF10A, MCF7, and MDA-MB231 cells, [18F]FDG, 6-deoxy-6-[18F]fluoro-d-fructose (6-[18F]FDF) and [18F]-fluoroazomycin arabinoside were used in radiotracer experiments, whereas GLUT1/2/5 mRNA was analyzed with real-time PCR and protein levels determined via Western blot/immunohistochemistry. Positron emission tomography imaging was performed in MCF7 and MDA-MB231 tumor-bearing mice. Glucose/fructose/cytochalasin B reduced cellular 6-[18F]FDF uptake by 50%, indicating functional involvement of GLUT2. With GLUT5 staining lower than GLUT1, 6-[18F]FDF revealed lower uptake than [18F]FDG [standardized uptake value (SUV)6-[18F]FDF, 120 min 0.77 ± 0.06 vs. SUV[18F]FDG, 120 min 1.08 ± 0.07] in MDA-MB231 tumors and was blocked by 20% with cytochalasin B after 10 min. Whereas correspondence between 6-[18F]FDF uptake and GLUT5 protein was low, high GLUT2 levels were detected in all cell lines and tumor models. Besides GLUT1, GLUT5 seems to be regulated under hypoxia on the molecular and functional level. Additionally, results strongly support a functional involvement of GLUT2 in fructose metabolism, possibly by compensating for the weaker expression and function of GLUT5 in BC.-Hamann, I., Krys, D., Glubrecht, D., Bouvet, V., Marshall, A., Vos, L., Mackey, J. R., Wuest, M., Wuest, F. Expression and function of hexose transporters GLUT1, GLUT2, and GLUT5 in breast cancer-effects of hypoxia.

The epidemiological studies have shown that antibiotic treatment increases the susceptibility to inflammatory bowel disease development. The disturbance of mucus layer integrity might be one of the possible mechanisms. The aim of the present study was to investigate the effect of antibiotic ceftriaxone treatment on glycoproteins level and its carbohydrate composition in surface mucus layer of rat intestine. The study was done on male Wistar rats (140-160 g). Ceftriaxone (300 mg/kg, i.m.) was administered once a day for 14 days. The surface mucus from terminal ileum and colon were collected on the 15th, 29th and 72nd days of the experiment. Total level of mucus glycoproteins, hexoses, hexosamines, fucose and sialic acids were measured. Ceftriaxone administration did not affect the levels of glycoproteins in rat ileum. In the colon, the levels of glycoprotein were 1.3-fold decreased (Р < 0.05) on the 72nd day of the experiment. These changes were accompanied by the 1.2-fold decrease of hexoses (Р < 0.05) and 3.1-fold (Р < 0.05) decrease of fucose level and 1.5-fold (Р < 0.05) increase of the levels of sialic acids in the surface mucus of the rat colon. Thus, ceftriaxone administration induces the long-term changes in the levels of glycoproteins and carbohydrates composition in the rat colon surface mucus. This could potentially explain the susceptibility to inflammatory bowel disea­ses development.

Use of [18F]FDG-positron emission tomography (PET) in clinical breast cancer (BC) imaging is limited mainly by insufficient expression levels of facilitative glucose transporter (GLUT)1 in up to 50% of all patients. Fructose-specific facilitative hexose transporter GLUT5 represents an alternative biomarker for PET imaging of hexose metabolism in BC. The goal of the present study was to compare the uptake characteristics of selected hexose-based PET radiotracers in murine BC model EMT6. Uptake of 1-deoxy-1-[18F]fluoro-d-fructose (1-[18F]FDF), 6-deoxy-6-[18F]fluoro-d-fructose (6-[18F]FDF), 1-deoxy-1-[18F]fluoro-2,5-anhydro-mannitol (1-[18F]FDAM), 2-deoxy-2-[18F]fluoro-d-glucose (2-[18F]FDG), and 6-deoxy-6-[18F]fluoro-d-glucose (6-[18F]FDG) was studied in EMT6 cells, tumors, and muscle and correlated to GLUT1 and GLUT5 expression levels. Fructose-derivative 6-[18F]FDF revealed greater tumor uptake than did structural analog 1-[18F]FDF, whereas 1-[18F]FDAM with locked anomeric configuration showed similar low tumor uptake to that of 1-[18F]FDF. Glucose-derivative 6-[18F]FDG reached maximum tumor uptake at 20 minutes, with no further accumulation over time. Uptake of 2-[18F]FDG was greatest and continuously increasing owing to metabolic trapping through phosphorylation by hexokinase II. In EMT6 tumors, GLUT5 mRNA expression was 20,000-fold lower compared with GLUT1. Whereas the latter was much greater in tumor than in muscle tissue (GLUT1 50:1), the opposite was found for GLUT5 mRNA expression (GLUT5 1:6). GLUT5 protein levels were higher in tumor versus muscle tissue as determined by Western blot and immunohistochemistry. Our data suggest that tumor uptake of fructose metabolism-targeting radiotracers 1-[18F]FDF, 6-[18F]FDF, and 1-[18F]FDAM does not correlate with GLUT5 mRNA levels but is linked to GLUT5 protein levels. In conclusion, our results highlight the importance of detailed biochemical studies on GLUT protein expression levels in combination with PET imaging studies for functional characterization of GLUTs in BC.

The current article presents recent findings on the metabolic effects of fructose.Fructose has always been considered as a simple 'caloric' hexose only metabolized by splanchnic tissues. Nevertheless, there is growing evidence that fructose acts as a second messenger and induces effects throughout the human body.Recent discoveries made possible with the evolution of technology have highlighted that fructose induces pleiotropic effects on different tissues. The fact that all these tissues express the specific fructose carrier GLUT5 let us reconsider that fructose is not only a caloric hexose, but could also be a potential actor of some behaviors and metabolic pathways. The physiological relevance of fructose as a metabolic driver is pertinent regarding recent scientific literature.

The importance of the hydrogen bonding interactions in the GLUT-hexose binding process (GLUT=hexose transporter) has been demonstrated by studying the binding of structurally modified d-fructose analogues to GLUTs, and in one case its transport into cells. The presence of a hydrogen bond donor at the C-3 position of 2,5-anhydro-d-mannitol derivatives is essential for effective binding to GLUT5 and transport into tumor cells. Surprisingly, installation of a group that can function only as a hydrogen bond acceptor at C-3 resulted in selective recognition by GLUT1 rather than GLUT5. A fluorescently labelled analogue clearly showed GLUT-mediated transport and low efflux properties of the probe. This study reveals that a single positional modification of a 2,5-anhydro-d-mannitol derivative is sufficient to switch its binding preference from GLUT5 to GLUT1, and uncovers general scaffolds that are suitable for the potential selective delivery of molecular payloads into tumor cells via GLUT transport machinery.

The presence of a mixture of progestogens at ng/L concentration levels in surface waters is a worldwide problem. Only a few studies explore the effect of progestogen treatment in a mixture as opposed to individual chemicals to shed light on how non-target species respond to these contaminants. In the present study, we used an invertebrate model species, Lymnaea stagnalis, exposed to a mixture of four progestogens (progesterone, levonorgestrel, drospirenone, and gestodene) in 10ng/L concentration for 3 weeks. Data at both physiological and cellular/molecular level were analyzed using the ELISA technique, stereomicroscopy combined with time lapse software, and capillary microsampling combined with mass spectrometry. The treatment of adult Lymnaeas caused reduced egg production, and low quality egg mass on the first week, compared to the control. Starting from the second week, the egg production, and the quality of egg mass were similar in both groups. At the end of the third week, the egg production and the vitellogenin-like protein content of the hepatopancreas were significantly elevated in the treated group. At the cellular level, accelerated cell proliferation was observed during early embryogenesis in the treated group. The investigation of metabolomic changes resulted significantly elevated hexose utilization in the single-cell zygote cytoplasm, and elevated adenylate energy charge in the egg albumen. These changes suggested that treated snails provided more hexose in the eggs in order to improve offspring viability. Our study contributes to the knowledge of physiological effect of equi-concentration progestogen mixture at environmentally relevant dose on non-target aquatic species.

Enzymatic hydrolysis of lactose is a crucial step to improve the efficiency and selectivity of membrane-based separations toward the recovery of milk oligosaccharides free from simple sugars. Response surface methodology was used to investigate the effects temperature (25.9 to 54.1 &deg, C) and amount of enzyme (0.17 to 0.32% w/w) at 1, 2, and 4 h of reaction on the efficiency of lactose hydrolysis by Aspergillus oryzae &beta, galactosidase, preservation of major goat whey oligosaccharides, and on the de-novo formation of oligosaccharides. Lactose hydrolysis above 99% was achieved at 1, 2, and 4 h, not being significantly affected by temperature and amount of enzyme within the tested conditions. Formation of 4 Hexose (Hex) and 4 Hex 1 Hex and an increased de-novo formation of 2 Hex 1 N-Acetyl-Neuraminic Acid (NeuAc) and 2 Hex 1 N-Glycolylneuraminic acid (NeuGc) was observed in all treatments. Overall, processing conditions using temperatures &le, 40 &deg, C and enzyme concentration &le, 0.25% resulted in higher preservation/formation of goat whey oligosaccharides.

Calorie restriction (CR) can prolong the human lifespan, but enforcing long-term CR is difficult. Therefore, a compound that reproduces the effect of CR without CR is needed. In this review, we summarize the current knowledge on compounds with CR mimetic (CRM) effects. More than 10 compounds have been listed as CRMs, some of which are conventionally categorized as upstream-type CRMs showing glycolytic inhibition, while the others are categorized as downstream-type CRMs that regulate or genetically modulate intracellular signaling proteins. Among these, we focus on upstream-type CRMs and propose their classification as compounds with energy metabolism inhibition effects, particularly glucose metabolism modulation effects. The upstream-type CRMs reviewed include chitosan, acarbose, sodium-glucose cotransporter 2 inhibitors, and hexose analogs such as 2-deoxy-d-glucose, d-glucosamine, and d-allulose, which show antiaging and longevity effects. Finally, we discuss the molecular definition of upstream-type CRMs.

To test the effect of adding different monosaccharide groups to a non-phloem-mobile insecticide on the phloem mobility of the insecticide, a series of conjugates of different monosaccharides and fipronil were synthesized using the trichloroacetimidate method. Phloem mobility tests in castor bean ( Ricinus communis L.) seedlings indicated that the phloem mobility of these conjugates varied markedly. L-Rhamnose-fipronil and D-fucose-fipronil displayed the highest phloem mobility among all of the tested conjugates. Conjugating hexose, pentose, or deoxysugar to fipronil through an O-glycosidic linkage can confer phloem mobility to fipronil in R. communis L. effectively, while the -OH orientation of the monosaccharide substantially affected the phloem mobility of the conjugates.

Objective To investigate the protective role of Cardiospermum halicacabum (C. halicacabum) leaf extract on glycoprotein metabolism in streptozotocin (STZ)-induced diabetic rats. Methods Diabetes was induced in male albino Wistar rats by intraperitonial administration of STZ. The C. halicacabum leaf extract (CHE) was administered orally to normal and STZ–diabetic rats for 45 days. The effects of C. halicacabum leaf extract (CHE) on plasma and tissue glycoproteins (hexose, hexosamine, fucose and sialic acid) were determined. Results The levels of plasma and tissues glycoproteins containing hexose, hexosamine and fucose were significantly increased in STZ–induced diabetic rats. In addition, the level of sialic acid significantly increased in plasma and liver while decreased in kidney of STZ–induced diabetic rats. After administration of CHE to diabetic rats, the metabolic alteration of glycoprotein reverted towards normal levels. Conclusions The present study indicates that the CHE possesses a protective effect on abnormal glycoprotein metabolism in addition to its antihyperglycemic activity.

Plasmodium falciparum requires glucose as its energy source to multiply within erythrocytes but is separated from plasma by multiple membrane systems. The mechanism of delivery of substrates such as glucose to intraerythrocytic parasites is unclear. We have developed a system for robust functional expression in Xenopus oocytes of the P. falciparum asexual stage hexose permease, PfHT1, and have analyzed substrate specificities of PfHT1. We show that PfHT1 (a high-affinity glucose transporter, K m ≈ 1.0 mM) also transports fructose ( K m ≈ 11.5 mM). Fructose can replace glucose as an energy source for intraerythrocytic parasites. PfHT1 binds fructose in a furanose conformation and glucose in a pyranose form. Fructose transport by PfHT1 is ablated by mutation of a single glutamine residue, Q169, which is predicted to lie within helix 5 of the hexose permeation pathway. Glucose transport in the Q169N mutant is preserved. Comparison in oocytes of transport properties of PfHT1 and human facilitative glucose transporter (GLUT)1, an archetypal mammalian hexose transporter, combined with studies on cultured P. falciparum , has clarified hexose permeation pathways in infected erythrocytes. Glucose and fructose enter erythrocytes through separate permeation pathways. Our studies suggest that both substrates enter parasites via PfHT1.

Whether nectarivores or frugivores place selective pressure on the plants they feed on, in terms of nectar or fruit traits, is much debated. Globally sugar preferences, concentration preference and digestive ability of avian nectarivores have been extensively researched. In contrast, relatively little is known about mammalian nectarivores or frugivores in terms of these, particularly Old World species. Consequently effect of sugar type and concentration on food preference in Wahlberg's epauletted fruit bat Epomophorus wahlbergi was investigated. Pair-wise choice tests were conducted using equicaloric hexose and sucrose solutions at five different concentrations (5%-25%). It was expected that they would prefer hexose sugars as these are dominant in available indigenous fruits. However, bats preferred hexoses only when offered dilute (5%) concentrations. From 10% to 25% they showed a decrease in volume intake. Their body mass was generally higher and similar after feeding during the night with the exception of 5% concentration where the mean body mass decreased. When E. wahlbergi were offered a range of sucrose or hexose solutions (10%-25%) respectively, they showed no concentration preference in terms of total volume consumed, nor energy intake. These findings suggest that these fruit bats do not appear to act as a selective pressure on sugar composition in Old World fruit. In fruit bats with high energy requirements, dietary flexibility may be an advantage when faced with seasonal and unpredictable fruit availability.

A polyhydric alcohol (PAL) was isolated from Taxus cuspidata and its immunostimulatory activities were assessed. The primary monosaccharide composition of the PAL was determined to be glucose, where HPAEC analysis showed no significant amount of any other sugars. However, glycerol and xylitol were identified as the main sugar alcohols. Fourier-transform infrared (FT-IR) analysis indicated that the purified PAL is a complex glycitol, which structurally contains significant amount of hydroxyl groups. MALDI-TOF mass spectroscopy also demonstrated that PAL is a complex glycitol built in hexose polymerization. Enzyme linked immunosorbent assay showed that the PAL stimulates the release of the proinflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. Furthermore, treatment of RAW 264.7 cells with PAL for 24h remarkably increased the phosphorylation levels of ERK, p38 and JNK in a dose-dependent manner, whereas the total protein levels of ERK (t-ERK), p38 (t-p38) and JNK (t-JNK) remained unchanged. These results clearly demonstrate that PAL stimulates the immune response in RAW 264.7 cells through the activation of MAPKs (ERK, p38 and JNK) signaling pathway. To the best of our knowledge, this is the first study to demonstrate the primary structure and immune-stimulating activities of PAL from the fruit of T. cuspidata.

Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound, 3-hydroxymethyl xylitol (3-HMX), has been isolated, and its optimum dose has been determined in a short duration study and patented. In addition, the long-term effect of 3-HMX in type 2 diabetic rats on antihyperglycemic, antioxidants, antihyperlipidemic, and protein metabolism and kidney marker enzymes was investigated, and its effect was shown previously. In this study, we investigated the effect of 3-HMX on plasma and tissue glycoproteins in streptozotocin-diabetic rats. Animals were divided into five groups viz., control group, 3-HMX (40 mg/kg of body weight) treated group, diabetic group, diabetic+3-HMX (40 mg/kg of body weight), and diabetic+glibenclamide (600 μg/kg of body weight). 3-HMX was administered orally at a dose of 40 mg/kg of body weight for 45 days. The study shows significant increases in the level of sialic acid except kidney and elevated levels of hexose, hexosamine, and fucose in the liver and kidney of diabetic rats, and the treatment with 3-HMX and glibenclamide showed reversal of these parameters toward normalcy. Thus, the study indicates that 3-HMX possesses a significant beneficial effect on glycoprotein components.

We are investigating non-absorbable polymeric conjugates bearing glucosides via a ω-amino triethylene glycol linker as oral anti-diabetic drugs that suppress an increase in the blood glucose level after meals through inhibition of Na+/glucose cotransporter (SGLT1). When the linker was bound to phloridzin, which is a SGLT1 inhibitor, to yield a precursor of the conjugate, the in vitro inhibitory effect on SGLT1-mediated d -glucose uptake was reduced to about one-tenth that of phloridzin. The inhibitory effect was recovered completely when the precursor was immobilized on the surface of poly(amidoamine) (PAMAM) dendrimers (generation: 3.0) by coupling with one-eighth or less of the terminal carboxyl groups. We considered that the phloridzin-derived glucose moiety on the dendrimer surface was prerequisite for SGLT1 inhibition but that the aglycon part was not always required for the inhibition. Commercially used arbutin, a SGLT1 substrate, was substituted for phloridzin whose aglycon is composed of toxic phloretin. The in vitro inhibitory effect of arbutin was about one-thirtieth that of intact phloridzin; however, the inhibitory effect of the PAMAM dendrimer–arbutin conjugates was as strong as that of the PAMAM dendrimer–phloridzin conjugates. Rat experiments further showed that the PAMAM dendrimer–arbutin conjugates significantly suppressed d -glucose-induced hyperglycemic effects. The dendritic conjugate bearing arbutin appears to be a good candidate as an oral anti-diabetic drug.

SUMMARYRecent research has shown that nectar properties of flowers pollinated by generalist avian nectarivores differ markedly from those of flowers pollinated by specialist avian nectarivores. In particular, flowers pollinated by generalist avian nectarivores tend to have very dilute nectar dominated by hexose sugars. To establish whether pollinator-mediated selection can explain these traits, we tested nectar sugar preferences and digestive capabilities of the village weaver (Ploceus cucullatus), a common generalist passerine nectarivore in South Africa. When offered pairwise choices of equicaloric hexose and sucrose solutions, village weavers preferred hexose solutions at 5% and 10% sucrose equivalents (SE) but did not show significant preference for either type of sugar when higher concentrations were offered (15%, 20% and 25% SE). Birds were less efficient at absorbing sucrose than hexose sugars, as revealed by high-performance liquid chromatography (HPLC) analysis of excreta sugar content. This was true at both concentrations tested (8.22% and 25%), although apparent sucrose assimilation rates were still relatively high (89.6±2.9% at low concentrations and 93.6±1.7% at high concentrations). Transit times indicated that sucrose also passes through the digestive tract faster than hexose sugars, particularly when consumed at high concentrations. This may limit the rate at which sucrose can be hydrolyzed before absorption. These results indicate that hexose preferences in generalist avian nectarivores may help explain the low sucrose content in flowers pollinated by these birds. Moreover, the preference for hexose sugars in weavers was most evident at the low concentrations (ca. 9% sugar by mass) that are typical of nectar in flowers pollinated by generalist avian nectarivores.

Summary A Plasmodium falciparum hexose transporter (PfHT) has previously been shown to be a facilitative glucose and fructose transporter. Its expression in Xenopus laevis oocytes and the use of a glucose analogue inhibitor permitted chemical validation of PfHT as a novel drug target. Following recent re-annotations of the P. falciparum genome, other putative sugar transporters have been identified. To investigate further if PfHT is the key supplier of hexose to P. falciparum and to extend studies to different stages of Plasmodium spp., we functionally analysed the hexose transporters of both the human parasite P. falciparum and the rodent parasite Plasmodium berghei using gene targeting strategies. We show here the essential function of pfht for the erythrocytic parasite growth as it was not possible to knockout pfht unless the gene was complemented by an episomal construct. Also, we show that parasites are rescued from the toxic effect of a glucose analogue inhibitor when pfht is overexpressed in these transfectants. We found that the rodent malaria parasite orthologue, P. berghei hexose transporter (PbHT) gene, was similarly refractory to knockout attempts. However, using a single cross-over transfection strategy, we generated transgenic P. berghei parasites expressing a PbHT-GFP fusion protein suggesting that locus is amenable for gene targeting. Analysis of pbht-gfp transgenic parasites showed that PbHT is constitutively expressed through all the stages in the mosquito host in addition to asexual stages. These results provide genetic support for prioritizing PfHT as a target for novel antimalarials that can inhibit glucose uptake and kill parasites, as well as unveiling the expression of this hexose transporter in mosquito stages of the parasite, where it is also likely to be critical for survival.

Here we have investigated the inhibitory properties of green tea catechins on the Plasmodium falciparum hexose transporter (PfHT), the Babesia bovis hexose transporter 1 (BboHT1) and the mammalian facilitative glucose transporters, GLUT1 and GLUT5, expressed in Xenopus laevis oocytes. (-)-Epicatechin-gallate (ECG) and (-)-epigallocatechin-gallate (EGCG) inhibited D-glucose transport by GLUT1 and PfHT, and D-fructose transport by GLUT5, with apparent K(i) values between 45 and 117 microM. BboHT1 was more potently inhibited by the ungallated catechins (-)-epicatechin (EC) and (-)-epigallocatechin (EGC), with apparent K(i) values of 108 and 168 microM, respectively. Site-directed mutagenesis experiments provided little further support for previously reported models of catechin binding to hexose transporters. Furthermore, P. falciparum growth inhibition by catechins was not affected by the external D-glucose concentration. Our results provide new data on the inhibitory action of catechins against sugar transporters but were unable to elucidate the antimalarial mechanism of action of these agents.

Post-receptor signalling molecules that convey the signal from the activated insulin receptor to the actual process of Glut4 translocation and hexose uptake are poorly understood. Various studies have suggested a requirement of the lipid kinase phosphatidylinositol-3 kinase (P13-kinase) in this process. PI3kinase regulates the activation status of the small GTP-binding protein Rac which, in turn, is able to activate another G-protein Rho. Rac and Rho are known to regulate the structure of the membrane- and cytoplasmic actin-cytoskeleton. We have examined whether Rac and Rho transfer the signals generated by PI3kinase towards insulin-stimulated hexose uptake. For that purpose, we expressed in 3T3-L1 adipocytes the dominant-negative mutant of Rac N17 using vaccinia virus-mediated gene transfer. The expression levels of the Rac N17 protein were monitored by Western blotting. The abrogation of endogenous Rac signalling by expression of Rac N17 was inferred from the observed loss of arachidonic acid release in response to insulin. Basal and insulin-stimulated hexose transport were not affected by expression of the Rac Nl7 mutant. A possible contribution of Rho.GTP to stimulation of hexose uptake was examined by pre-incubation of adipocytes with lysophosphatidic acid (LPA). We observed a profound effect of LPA on the structure of the cytoskeleton and on the phosphorylation of Focal Adhesion Kinase (p125 FAK ), indicating that 3T3-L1 adipocytes respond to LPA and that Rho was activated by LPA. However, no effect was detected on the basal or on the insulin-stimulated hexose transport. We conclude that Rac and Rho are unlikely to be involved in insulin-stimulated hexose transport, suggesting a possible contribution of other signalling pathways, downstream of PI3kinase to this process.

Although fructose is commonly used as a sweetener, its effects on brain function are unclear. Using rat hippocampal slices, we found that fructose and mannose, like pyruvate, preserve ATP levels during 3-h of glucose deprivation. Similarly, fructose and mannose restored synaptic potentials (excitatory postsynaptic potential, EPSPs) depressed during glucose deprivation. However, restoration of synaptic responses was slow and only partial with fructose. EPSPs supported by mannose were inhibited by cytochalasin B (CCB), a glucose transport inhibitor, but were not inhibited by alpha-cyano-4-hydroxycinnamate (4-CIN), a monocarboxylate transport inhibitor, indicating that neurons use mannose via glucose transporters. In contrast, both CCB and 4-CIN depressed EPSPs supported by fructose, suggesting that fructose may be taken up by non-neuronal cells through CCB sensitive hexose transporters and metabolized to a monocarboxylate for subsequent use during neuronal respiration. Supporting this possibility, 20 minutes of oxygen deprivation in the presence of fructose resulted in functional and morphological deterioration whereas oxygen deprivation in the presence of glucose or mannose had minimal toxic effects. These results indicate that neuronal fructose utilization differs from glucose and mannose and likely involves release of monocarboxylates from glia.

Background The role of neural regulation in expression and function of intestinal hexose transporters is unknown. The aim of this study is to determine the role of intestinal innervation in gene expression and function of the membrane hexose transporters, SGLT1, GLUT2, and GLUT5 in the enterocyte. We hypothesize that denervation of the small intestine decreases expression of hexose transporters, which leads to decreased glucose absorption. Methods Six groups of Lewis rats were studied ( n = 6 each) as follows: control, 1 week after sham laparotomy, 1 and 8 weeks after syngeneic (no immune rejection) orthotopic small-bowel transplantation (SBT) (SBT1 and SBT8) to induce complete extrinsic denervation, and 1 and 8 weeks after selective disruption of intrinsic neural continuity to jejunoileum by gut transection and reanastomosis (T/A1 and T/A8). All tissue was harvested between 8 am and 10 am . In duodenum, jejunum, and ileum, mucosal messenger RNA (mRNA) levels were quantitated by real-time polymerase chain reaction (PCR), protein by Western blotting, and transporter-mediated glucose absorption using the everted sleeve technique. Results Across the 6 groups, the relative gene expression of hexose transporter mRNA and protein levels were unchanged, and no difference in transporter-mediated glucose uptake was evident in any region. The glucose transporter affinity (K m ) and functional transporter levels (V max ) calculated for duodenum and jejunum showed no difference among the 6 groups. Conclusion Baseline regulation of hexose transporter function is not mediated tonically by intrinsic or extrinsic neural continuity to the jejunoileum.

Certain glycan motifs in glycoproteins are involved in several biological events and diseases. To understand the roles of these motifs, a method is needed to identify the glycoproteins that carry them. We previously demonstrated that liquid chromatography-multiple-stage mass spectrometry (LC-MSn) allowed for differentiation of oligosaccharides attached to Lewis-motifs, such as Lewisx(Lex, Galbeta1-4(Fucalpha1-3)GlcNAc) from other glycans. We successfully discriminated Lex-conjugated oligosaccharides from other N-linked oligosaccharides derived from mouse kidney proteins by using Lewis-motif-distinctive ions, a deoxyhexose (dHex)+hexose (Hex)+N-acetylhexsosamine (HexNAc) fragment (m/z 512), and a Hex+HexNAc fragment (m/z 366). In the present study, we demonstrated that this method could be used to identify the Lex-conjugated glycoproteins. All proteins in the mouse kidney were digested into peptides, and the fucosylated glycopeptides were enriched by lectin-affinity chromatography. The resulting fucosylated glycopeptides were subjected to two different runs of LC-MSn using a Fourier- transform ion cyclotron resonance mass spectrometer (FTICR-MS) and an ion trap-type mass spectrometer. After the first run, we picked out product ion spectra of the expected Lex-conjugated glycopeptides based on the presence of Lewis-motif-distinctive ions and assigned a peptide+HexNAc or peptide+(dHex)HexNAc fragment in each spectrum. Then the fucosylated glycopeptides were subjected to a second run in which the peptide-related fragments were set as precursor ions. We successfully identified gamma-glutamyl transpeptidase 1 (gamma-GTP1), low-density lipoprotein receptor-related protein 2 (LRP2), and a cubilin precursor as Lex-conjugated glycoproteins by sequencing of 2-5 glycopeptides. In addition, it was deduced that cadherin 16, dipeptidase I, H-2 class I histocompatibility antigen, K-K alpha precursor (H2-Kk), and alanyl (membrane) aminopeptidase could be Lex-conjugated glycoproteins from the good agreement between the experimental and theoretical masses and fragment patterns. The results indicated that our method could be applicable for the identification and screening of glycoproteins carrying target glycan-motifs, such as Lewis epitopes.

Oligofructose, a natural food ingredient, is the product of partial enzymatic hydrolysis of inulin. This nondigestible oligosaccharide is fermented by colonic bacteria to produce mainly short-chain fatty acids, L-lactate, and CO2 and the energy necessary for bacterial growth. It also increases fecal mass. Based on biochemical balance charts for carbon atoms, metabolic pathways, and energy yield to the host, the caloric value of a fructosyl unit of oligofructose is calculated to be 25-35% that of a digested molecule of hexose. The caloric value of oligofructose is thus likely to be close to 1 kcal/g.

The optimal conditions for the hydrolysis of hexose and hexosamine components in the mucosaccharide fraction of red cell stroma were found to be 2 N HCl at 92° C. for 3 hours. The hydrolysate of stroma was converted by concentration, neutralization and ion exchange technique to a form in which the hexose and hexosamine components could be assertained. By determining the recovery and standard deviation the methods were found reproduceable. The normal values of total aldohexose, galactose, glucose and hexosamine concentrations were determined in stroma in about 20 cases of each of the following species: human, bovine, pig, and horse. The stroma was divided into two parts with a chloro-form-methanol mixture (2:1) and the hexose and hexosamine concentrations in each part were determined. Pig stroma, contrary to that of the other species, had markedly more hexoses in the lipid fraction than in the stroma residue fraction. The content of glucose in both fractions was the same in human stroma, but there were more hexoses and hexosamines in the stroma residue fraction. The hexosamine content in the lipid extract fraction of horse and human stroma was very low.

Five subfractions were isolated on DEAE-cellulose from samples of a commercially available human transferrin preparation and their carbohydrate composition was analysed. Hexosamine, galactose and total hexose were determined in four subfractions and sialic acid in all five. The data obtained indicate that the excess number of electrophoretic bands observed in transferrin from this source is due to the loss of carbohydrates which only affects sialic acid and none of the other sugar types. The availability of the penultimate galactose residues as the terminal residues in the subfractions deficient in sialic acid was also confirmed by a biological test utilizing the rat liver. The reason for the gradual loss of sialic acid from transferrin is unknown. Freezing-thawing and lyophilization did not detectably affect the sialic acid content of purified transferrin. However, free sialic acid did appear in some preparations on storage. It is concluded that similar changes in the carbohydrate composition of other plasma glycoproteins before, during, or after purification can be expected to exert an adverse effect on their usefulness as metabolic tracers.

Expression and function of hexose transporters vary diurnally in rat small intestine; however, this subject remains unexplored in mice.The aim of the study was to investigate the diurnal expression and function of hexose transporters SGLT1, GLUT2, and GLUT5 in mouse small bowel.Twenty-four c57bl6 mice maintained in a 12-h light/dark room (6 AM: -6 PM: ) were sacrificed at 9 AM: , 3 PM: , 9 PM: , and 3 AM: (n = 6 each). In duodenal, jejunal, and ileal mucosa, total cellular mRNA and protein levels were quantitated by real-time PCR and semiquantitative Western blotting, respectively. The everted sleeve technique measured transporter-mediated glucose uptake at 9 AM: and 9 PM: .mRNA expression of SGLT1, GLUT2, and GLUT5 varied diurnally in all three intestinal segments (por= 0.03). SGLT1, GLUT2, and GLUT5 protein levels varied diurnally in duodenum and jejunum (p0.05) but not in ileum. Transporter-mediated glucose uptake was greater at 9 PM: than 9 AM: (por= 0.04) in all three segments. V (max) was greater in duodenum (10 vs 6 nmol/cm/s) and jejunum (8 vs 5 nmol/cm/s) at 9 PM: compared to 9 AM: (p = 0.01); K (m) remained unchanged. mRNA levels of intestinal hexose transporters varied diurnally. Protein levels peaked 6-12 h later during dark cycle when70% of food intake occurred; glucose transport followed a similar pattern with increased uptake at 9 PM: .Hexose transporter expression and function vary diurnally with nocturnal feeding patterns of mice.

Babesia are tick-transmitted haemoprotozoan parasites that infect cattle, with an estimated 500 million at risk worldwide. Here, two predicted hexose transporters (BboHT1 and 2) have been identified within the Babesia bovis genome. BboHT1, having 40% and 47% amino acid sequence similarity compared with the human (GLUT1) and Plasmodium falciparum (PfHT) hexose transporters, respectively, is the only one that could be characterised functionally after expression in Xenopus laevis oocytes. Radiotracer studies on BboHT1 showed that it is a saturable, Na(+)-independent, stereo-specific hexose transporter, with a K(m) value for glucose of 0.84+/-0.54 mM (mean+/-SEM). Using D-glucose analogues, hydroxyl positions at O-4 and O-6 have been identified as important for ligand binding to BboHT1. D-glucose transport was inhibited maximally by cytochalasin B (50 microM). A long-chain O-3 hexose derivative (compound 3361) that selectively inhibits PfHT also inhibited relatively potently BboHT1, with an apparent K(i) value of 4.1+/-0.9 microM (mean+/-SEM). Compound 3361 did not inhibit B. bovis proliferation in in vitro growth assays but inhibited invasion of glucose-depleted bovine erythrocytes. Taken together with results of inhibition studies with cytochalasin B and beta-glucogallin, these data provide new insights into glucose metabolism of erythrocytic-stage Babesia infections.

The hexose transmembrane transporters SGLT1 and GLUT2 are present in low quantities in ileum where little glucose absorption occurs normally; however, glucose uptake in ileum is highly adaptable after small bowel resection.Ileal adaptability for glucose absorption after jejunal resection is mediated predominately by upregulation of GLUT2.Rats underwent 70% proximal-based jejunoileal resection. Transporter-mediated glucose uptake was measured in proximal and distal remnant ileum 1 and 4 wk postoperatively (n = 6 rats, each) and in corresponding ileal segments in control and 1 wk sham laparotomy rats (n = 6, each) without and with selective inhibitors of SGLT1 and GLUT2. In separate groups of rats (n = 6, each), protein (Western blots), mRNA (reverse transcriptase polymerase chain reaction [RT-PCR]), and villus height (histomorphology) were measured.After 70% proximal intestinal resection, there was no dramatic change in protein or mRNA expression per cell of either SGLT1 or GLUT2, but median glucose uptake (nmol/cm/min) increased markedly from 52 (range 28-63) in controls to 118 (range 80-171) at 1 wk, and 203 (range 93-248) at 4 wk (por = 0.04 each) correlating with change in villus height (por = 0.03).Ileal adaptation for glucose transport occurs through cellular proliferation (hyperplasia) and not through cellular upregulation of glucose transporters.

This study was designed to examine the impact of a principal component of hot red peppers and chilli peppers, capsaicin, on alterations in lipid peroxidation, membrane-bound enzyme profiles and glycoprotein levels during benzo(a)pyrene (BP)-induced lung cancer in Swiss albino mice. BP (50 mgkg−1) induced deleterious changes that were revealed by alterations in lipid peroxidation, membrane-bound enzyme (Na+/K+ATPase, Ca2+ATPase and Mg2+ATPase) activity, levels of total protein and protein-bound carbohydrate components (sialic acid, hexose, hexosamine, hexuronic acid and fucose). Pre-co-treatment with capsaicin (10 mgkg−1) restored the detrimental effects induced by BP, indicating its protective role in BP-induced lung cancer.

The ethanolic extracts of a mangrove plant Ceriops tagal (Family Rhizophoraceae) and its sequential fractions thereof were studied for their effect on 3H-2-deoxyglucose uptake by L6 rat muscle cells cultured to the myotube stage. Among these, the n-hexane soluble fraction of ethanolic extract of the leaves of C. tagal enhanced 3H-2-deoxyglucose uptake even at 2 microg mL(-1) concentration with half maximum activity at 10 microg mL(-1), comparable with insulin (1 microM) and metformin (400 microM). This enhancement in glucose uptake was found to be insulin independent and in contrast to insulin, its effect was also prevalent in undifferentiated myoblasts. It may be concluded from the results that n-hexane soluble fraction of ethanolic extract of C. tagal have the property to stimulate the glucose uptake, which might be a useful source for the isolation of new antihyperglycemic compounds.

Intestinal membrane permeability is an important factor affecting the bioavailability of drugs. As a strategy to improve membrane permeability, membrane transporters are useful targets since essential nutrients are absorbed efficiently via specific transporters. For example, there are reports that intestinal hexose transporters could be used as a tool to improve permeability; however, there has been no direct evidence that the transporter protein, sodium/glucose cotransporter 1 (SGLT1), is involved in the transport of hexose analogs. Accordingly, we examined directly whether the intestinal membrane permeability of hexose analogs can be improved by utilizing SGLT1. Three hexose-quinoline derivatives were synthesized and their interactions with SGLT1 were evaluated. Among the three derivatives, the glucose-quinoline molecule exhibited an inhibitory effect on D-glucose uptake by both rat intestinal brush-border membrane vesicles (BBMVs) and Xenopus oocytes expressing SGLT1. In addition, significant uptake of the glucose-quinoline derivative by Xenopus oocytes expressing SGLT1 was observed by both an electrophysiological assay and direct measurement of the uptake of the compound, while the galactose-quinoline derivative did not show significant uptake via SGLT1. Thus, it was directly demonstrated that SGLT1 could be used as a tool for the improvement of intestinal membrane permeability of drugs by modification to the glucose analogs.

To investigate the effect of mannose on lipopolysaccharide (LPS) induced acute lung injury (ALI) in rats.Ten groups of Sprague-Dawley rats were used: 1) the control group received an intratracheal instillation of saline, 2) the LPS group received an intratracheal instillation of LPS (3 mg/kg), 3-6) the mannose groups were injected i.v. with 15, 45, 135, and 405 mg/kg mannose, 7-9) the glucose, galactose, and fructose groups were injected with different hexoses (135 mg/kg), and 10) the dexamethasone (DXM) group was injected with DXM (2 mg/kg). In groups 2-8, LPS was administered after injection of drugs. Lung wet/dry weight ratio, permeability index (PPI), total leukocytes and polymorphonuclear neutrophils (PMNs) counts in bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) and superoxide dismutase (SOD) activity, tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 in lung and BALF were determined.Pre-treatment with mannose attenuated pulmonary edema and protein exudation in a dose-dependent manner, the maximal effect was similar to or greater than that of DXM. Mannose also prevented the inflammatory cell accumulation, although the maximal effect was weaker than that of DXM. Mannose was more effective than DXM in inhibiting MPO activity and restoring SOD activity. Moreover, it inhibited production of TNF-alpha and IL-10. Histological changes of the lungs were also ameliorated by mannose. There were no significant improvements observed in rats pre-treated with glucose, galactose or fructose.Mannose is effective in reducing LPS-induced ALI.

Earlier studies have shown a correlation between the presence of a 77 kDa protein in the proteins extracted from young adult Drosophila melanogaster (D.m.) and the autosomal longevity allele. A2 at the JmA locus. In this study, a 77 kDa protein has been isolated from pupae of D.m. of a long-lived strain of genotype A2A2, and was purified by DEAE chromatography, ConA column chromatography, and two cycles of gel filtration. The purified protein has a molecular weight of 76,600 (by SDS-PAGE), an isoelectric point of pH 6.5, and molar extinction coefficient A(280(1%) = 18.3. It is a glycoprotein containing 3.3% hexose. Supplementing the food of D.m. with the purified protein at 5 x 10(-4) micrograms/ml, beginning at day 5 after emergence, resulted in an increase in the survival rate and maximal life span of both short-lived and long-lived strains of D.m.

Hexose transporter mRNA and protein levels follow a diurnal rhythm in rat jejunum. Their coordinated expression and resultant function throughout the small bowel is not well understood. We hypothesized that hexose transporter levels and glucose absorption follow a coordinated, site-specific diurnal rhythm in rat duodenum and jejunum, but not in ileum.Sprague-Dawley rats were housed in a strictly maintained, 12-h, light/dark room [light 6 am to 6 pm] with free access to water and chow. Mucosa was harvested from duodenum, jejunum, and ileum at 3 am, 9 am, 3 pm, and 9 pm, and full thickness 1-cm segments were harvested at 9 am, and 9 pm (n = 6 for each segment at each time point). mRNA levels were determined by reverse-transcription, real-time polymerase chain reaction (nor = 5), protein levels by semiquantitative Western blotting (nor = 5), and transporter-mediated glucose uptake by everted sleeve technique (n = 6).mRNA levels of SGLT1 and GLUT5 followed a temporally coordinated, diurnal rhythm in all 3 segments (P.01), while mRNA for GLUT2 and protein levels for SGLT1 and GLUT2 varied diurnally only in duodenum and jejunum (P.05) but not in ileum (P.10). SGLT1 and GLUT5 mRNA induction decreased aborally. Baseline SGLT1 and GLUT5 mRNA levels and SLGT1 and GLUT2 protein levels did not vary aborally (P.05 for all). GLUT2 mRNA baseline levels were decreased in ileum (P.01). Glucose uptake varied diurnally in duodenum and jejunum with no difference in ileum. Transporter-mediated glucose uptake was greater in duodenum and jejunum compared with ileum.Regulation of hexose absorption in rat small bowel seems to be site-specific and mediated by multiple mechanisms.

Nectarivorous bats include very dilute nectar in their natural diet, and recent work with Pallas's long-tongued bat Glossophaga soricina showed that sugar (energy) intake rate decreased at dilute sucrose solutions. However, chiropterophillous nectar is composed mainly of the hexoses glucose and fructose. Because bats fed hexose nectar would save the delay of hydrolyzing sucrose, we hypothesized that sugar intake rate should be higher on this diet than on sucrose nectar. We compared intake response in Pallas's long-tongued bats offered 1 : 1 glucose-fructose (hexose) and sucrose diets at 5%, 10%, 20%, 30%, and 40% (mass/volume) sugar solutions. We also tested the hypothesis that sucrose hydrolysis limits food intake in bats. Intake response was the same in bats fed both types of diet: sugar intake rate was lower in dilute solutions and then increased with sugar concentration. Similar intake responses in both diets indicate that sucrose hydrolysis alone does not limit food intake and support the idea that the burden of processing excess water in dilute solutions plays a major role.

The metabolism of D-glucose was recently reported to be impaired in pancreatic islets from second generation rats depleted in long-chain polyunsaturated ω3 fatty acids. Considering the increased clearance of circulating non-esterified fatty acids prevailing in these rats, a possible inhibition of glucokinase in insulin-producing cells by endogenous long-chain fatty acyl-CoA was considered. The present study was mainly aimed at assessing the validity of the latter proposal. The activity of glucokinase in islet homogenates, as judged from the increase in D-glucose phosphorylation rate in response to a rise in the concentration of the hexose represented, in the ω3-depleted rats, was only 81.8 ± 4.8% (n = 11; p