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Sample records for augments glucose mediated

  1. High glucose augments stress-induced apoptosis in endothelial cells

    Institute of Scientific and Technical Information of China (English)

    Wenwen Zhong; Yang Liu; Hui Tian

    2009-01-01

    Hyperglycemia has been identified as one of the important factors involved in the microvascular complications of diabetes, and has been related to increased cardiovascular mortality. Endothelial damage and dysfunction result from diabetes; therefore, the aim of this study was to determine the response of endothelial cells to stressful stimuli, modelled in normal and high glucose concentrations in vitro. Eahy 926 endothelial cells were cultured in 5 mmol/L or 30 mmol/L glucose conditions for a 24 hour period and oxidative stress was induced by exposure to hydrogen peroxide (H2O2) or tumour necrosis factor- α (TNF- α ), following which the protective effect of the glucocorticoid dexamethasone was assessed. Apoptosis, necrosis and cell viability were determined using an ELISA for DNA fragmentation, an enzymatic lactate dehydrogenase assay and an MTT assay, respectively. High glucose significantly increased the susceptibility of Eahy 926 cells to apoptosis in the presence of 500 μmol/L H2O2, above that induced in normal glucose (P<0.02). A reduction of H2O2- and TNF- α -induced apoptosis occurred in both high and low glucose after treatment with dexametha-sone (P<0.05). Conclusion high glucose is effective in significantly augmenting stress caused by H2O2, but not in causing stress alone. These findings suggest a mechanism by which short term hyperglycemia may facilitate and augment endothelial damage.

  2. Histidine augments the suppression of hepatic glucose production by central insulin action.

    Science.gov (United States)

    Kimura, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-Ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime; Kaneko, Shuichi; Kasuga, Masato; Inoue, Hiroshi

    2013-07-01

    Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA levels and augmented HGP suppression by insulin. This suppression of hepatic gluconeogenesis by histidine was abolished by hepatic STAT3 deficiency or hepatic Kupffer cell depletion. Inhibition of HGP by histidine was also blocked by ICV administration of a histamine H1 receptor antagonist. Therefore, histidine activates hepatic STAT3 and suppresses HGP via central histamine action. Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H1 receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. These findings suggest that central histidine action is independent of central insulin action, while both have additive effects on HGP suppression. Our results indicate that central histidine/histamine-mediated suppression of HGP is a potential target for the treatment of type 2 diabetes.

  3. Berberine activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes.

    Science.gov (United States)

    Kim, So Hui; Shin, Eun-Jung; Kim, Eun-Do; Bayaraa, Tsenguun; Frost, Susan Cooke; Hyun, Chang-Kee

    2007-11-01

    It has recently been known that berberine, an alkaloid of medicinal plants, has anti-hyperglycemic effects. To explore the mechanism underlying this effect, we used 3T3-L1 adipocytes for analyzing the signaling pathways that contribute to glucose transport. Treatment of berberine to 3T3-L1 adipocytes for 6 h enhanced basal glucose uptake both in normal and in insulin-resistant state, but the insulin-stimulated glucose uptake was not augmented significantly. Inhibition of phosphatidylinositol 3-kinase (PI 3-K) by wortmannin did not affect the berberine effect on basal glucose uptake. Berberine did not augment tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate (IRS)-1. Further, berberine had no effect on the activity of the insulin-sensitive downstream kinase, atypical protein kinase C (PKCzeta/lambda). However, interestingly, extracellular signal-regulated kinases (ERKs), which have been known to be responsible for the expression of glucose transporter (GLUT)1, were significantly activated in berberine-treated 3T3-L1 cells. As expected, the level of GLUT1 protein was increased both in normal and insulin-resistant cells in response to berberine. But berberine affected the expression of GLUT4 neither in normal nor in insulin-resistant cells. In addition, berberine treatment increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 cells, which has been reported to be associated with GLUT1-mediated glucose uptake. Together, we concluded that berberine increases glucose transport activity of 3T3-L1 adipocytes by enhancing GLUT1 expression and also stimulates the GLUT1-mediated glucose uptake by activating GLUT1, a result of AMPK stimulation.

  4. Fructose augments infection-impaired net hepatic glucose uptake during TPN administration.

    Science.gov (United States)

    Donmoyer, C M; Ejiofor, J; Lacy, D B; Chen, S S; McGuinness, O P

    2001-05-01

    During chronic total parenteral nutrition (TPN), net hepatic glucose uptake (NHGU) and net hepatic lactate release (NHLR) are markedly reduced (downward arrow approximately 45 and approximately 65%, respectively) with infection. Because small quantities of fructose are known to augment hepatic glucose uptake and lactate release in normal fasted animals, the aim of this work was to determine whether acute fructose infusion with TPN could correct the impairments in NHGU and NHLR during infection. Chronically catheterized conscious dogs received TPN for 5 days via the inferior vena cava at a rate designed to match daily basal energy requirements. On the third day of TPN administration, a sterile (SHAM, n = 12) or Escherichia coli-containing (INF, n = 11) fibrin clot was implanted in the peritoneal cavity. Forty-two hours later, somatostatin was infused with intraportal replacement of insulin (12 +/- 2 vs. 24 +/- 2 microU/ml, SHAM vs. INF, respectively) and glucagon (24 +/- 4 vs. 92 +/- 5 pg/ml) to match concentrations previously observed in sham and infected animals. After a 120-min basal period, animals received either saline (Sham+S, n = 6; Inf+S, n = 6) or intraportal fructose (0.7 mg x kg(-1) x min(-1); Sham+F, n = 6; Inf+F, n = 5) infusion for 180 min. Isoglycemia of 120 mg/dl was maintained with a variable glucose infusion. Combined tracer and arteriovenous difference techniques were used to assess hepatic glucose metabolism. Acute fructose infusion with TPN augmented NHGU by 2.9 +/- 0.4 and 2.5 +/- 0.3 mg x kg(-1) x min(-1) in Sham+F and Inf+F, respectively. The majority of liver glucose uptake was stored as glycogen, and NHLR did not increase substantially. Therefore, despite an infection-induced impairment in NHGU and different hormonal environments, small amounts of fructose enhanced NHGU similarly in sham and infected animals. Glycogen storage, not lactate release, was the preferential fate of the fructose-induced increase in hepatic glucose disposal in

  5. Chronic Low Dose Fructose infusion Does Not Reverse Glucagon-Mediated Decrease in Hepatic Glucose Utilization

    Science.gov (United States)

    Johnson, Paulette M.; Chen, Sheng-Song; Santomango, Tammy S.; Williams, Phillip E; Lacy, D. Brooks; McGuinness, Owen P.

    2013-01-01

    Objective An adaptation to chronic total parenteral nutrition (TPN; 75% of non protein calories as glucose) is the liver becomes a major consumer of glucose with lactate release as a by-product. The liver is able to further increase liver glucose uptake when a small dose of fructose is acutely infused via the portal system. Glucagon, commonly elevated during inflammatory stress, is a potent inhibitor of glucose uptake by the liver during TPN. The aim was to determine if chronic fructose infusion could overcome the glucagon-mediated decrease in hepatic glucose uptake. Material/methods Studies were performed in conscious insulin-treated chronically catheterized pancreatectomized dogs that adapted to TPN for 33 h. They were then assigned to one of 4 groups: TPN (C), TPN + fructose (4.4 μmol·kg−1·min−1, F), TPN+ glucagon (0.2 pmol·kg−1·min−1, GGN), or a TPN + fructose and glucagon (F+GGN) for an additional 63h (33–96h). Insulin, fructose and glucagon were infused into the portal vein. During that period all animals received a fixed insulin infusion 0.4mU· kg−1·min−1 (33–96h) and the glucose infusion rates were adjusted to maintain euglycemia (6.6 mM). Results Chronic fructose infusion was unable to further enhance net hepatic glucose uptake (NHGU; μmol·kg−1·min−1) (31.1±2.8 vs. 36.1±5.0; C vs. F) nor was it able to overcome glucagon-mediated decrease in NHGU (10.0±4.4 vs. 12.2±3.9; GGN vs. F+GGN). Conclusion In summary, chronic fructose infusion cannot augment liver glucose uptake during TPN nor can it overcome the inhibitory effects of glucagon. PMID:20940071

  6. A New Amperometric Glucose Biosensor with Naphthol Green B as Mediator

    Institute of Scientific and Technical Information of China (English)

    Qin ZHAO; Ruo YUAN; Chang Li MO; Ya Qin CHAI; Xia ZHONG

    2004-01-01

    Naphthol green B was used, for the first time, as a new mediator in an amperometric glucose biosensor. It is a good mediator, promoting electron transfer from glucose oxidase to graphite electrode. The biosensor shows high sensitivity to glucose at low potential with response time of 30 seconds. The linear range is from 1.5 to 18 μmol/L glucose with detection limit of 0.5 μmol/L glucose.

  7. Continuous low-dose fructose infusion does not reverse glucagon-mediated decrease in hepatic glucose utilization.

    Science.gov (United States)

    Johnson, Paulette M; Chen, Sheng-Song; Santomango, Tammy S; Williams, Phillip E; Lacy, D Brooks; McGuinness, Owen P

    2011-06-01

    An adaptation to continuous total parenteral nutrition (TPN; 75% of nonprotein calories as glucose) is the liver becomes a major consumer of glucose with lactate release as a by-product. The liver is able to further increase liver glucose uptake when a small dose of fructose is acutely infused via the portal system. Glucagon, commonly elevated during inflammatory stress, is a potent inhibitor of glucose uptake by the liver during TPN. The aim was to determine if continuous fructose infusion could overcome the glucagon-mediated decrease in hepatic glucose uptake. Studies were performed in conscious, insulin-treated, chronically catheterized, pancreatectomized dogs that adapted to TPN for 33 hours. They were then assigned to 1 of 4 groups: TPN (C), TPN + fructose (4.4 μmol kg(-1) min(-1); F), TPN + glucagon (0.2 pmol kg(-1) min(-1); GGN), or TPN + fructose and glucagon (F + GGN) for an additional 63 hours (33-96 hours). Insulin, fructose, and glucagon were infused into the portal vein. During that period, all animals received a fixed insulin infusion of 0.4 mU·kg(-1)·min(-1) (33-96 hours); and the glucose infusion rates were adjusted to maintain euglycemia (6.6 mmol/L). Continuous fructose infusion was unable to further enhance net hepatic glucose uptake (in micromoles per kilogram per minute) (31.1 ± 2.8 vs 36.1 ± 5.0; C vs F), nor was it able to overcome glucagon-mediated decrease in net hepatic glucose uptake (10.0 ± 4.4 vs 12.2 ± 3.9; GGN vs F + GGN). In summary, continuous fructose infusion cannot augment liver glucose uptake during TPN; nor can it overcome the inhibitory effects of glucagon. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Augmented HR Repair Mediates Acquired Temozolomide Resistance in Glioblastoma.

    Science.gov (United States)

    Gil Del Alcazar, Carlos Rodrigo; Todorova, Pavlina Krasimirova; Habib, Amyn A; Mukherjee, Bipasha; Burma, Sandeep

    2016-10-01

    Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults and is universally fatal. The DNA alkylating agent temozolomide is part of the standard-of-care for GBM. However, these tumors eventually develop therapy-driven resistance and inevitably recur. While loss of mismatch repair (MMR) and re-expression of MGMT have been shown to underlie chemoresistance in a fraction of GBMs, resistance mechanisms operating in the remaining GBMs are not well understood. To better understand the molecular basis for therapy-driven temozolomide resistance, mice bearing orthotopic GBM xenografts were subjected to protracted temozolomide treatment, and cell lines were generated from the primary (untreated) and recurrent (temozolomide-treated) tumors. As expected, the cells derived from primary tumors were sensitive to temozolomide, whereas the cells from the recurrent tumors were significantly resistant to the drug. Importantly, the acquired resistance to temozolomide in the recurrent lines was not driven by re-expression of MGMT or loss of MMR but was due to accelerated repair of temozolomide-induced DNA double-strand breaks (DSB). Temozolomide induces DNA replication-associated DSBs that are primarily repaired by the homologous recombination (HR) pathway. Augmented HR appears to underpin temozolomide resistance in the recurrent lines, as these cells were cross-resistant to other agents that induced replication-associated DSBs, exhibited faster resolution of damage-induced Rad51 foci, and displayed higher levels of sister chromatid exchanges (SCE). Furthermore, in light of recent studies demonstrating that CDK1 and CDK2 promote HR, it was found that CDK1/2 inhibitors countered the heightened HR in recurrent tumors and sensitized these therapy-resistant tumor cells to temozolomide.

  9. Ferrocene Derivative Mediator Bonded Sol-gel Membrane Glucose Biosensor

    Institute of Scientific and Technical Information of China (English)

    XUAN, Guang-Shan; KIM, Moon-Chang; HER, Dae-Sung; LEE, Heung-Lark

    2006-01-01

    The sol-gel derived glucose biosensor was developed, and the sol-gel membrane was organically modified by N-(3-triethoxysilylpropyl)-ferrocenylmethylamine (FcSi) as sol-gel precursor to make electrochemical biosensor.The structure of biosensor was sol-gel/FcSi+Gox/GC type (glucose oxidase, Gox). The ferrocene mediator was chemically immobilized to the silane network, and Gox was entrapped to the sol-gel glass network. Therefore,these structures prevented mediator leakage and retained the enzyme activity. Additionally, pH of electrolyte, temperature effects, and interference of positive substances with biosensor were investigated. And the electrochemical performance of biosensor was studied by amperometry. The results indicated that the linear range, detection limit,and response slope of biosensor was 2.00× 10-4-1.57× 10-3 mol·L-1, 2.0× 10-4 mol·L-1 and 5.06× 105 nA·mol-1 · L, respectively.

  10. ERK2-mediated phosphorylation of transcriptional coactivator binding protein PIMT/NCoA6IP at Ser298 augments hepatic gluconeogenesis.

    Science.gov (United States)

    Kapadia, Bandish; Viswakarma, Navin; Parsa, Kishore V L; Kain, Vasundhara; Behera, Soma; Suraj, Sashidhara Kaimal; Babu, Phanithi Prakash; Kar, Anand; Panda, Sunanda; Zhu, Yi-jun; Jia, Yuzhi; Thimmapaya, Bayar; Reddy, Janardan K; Misra, Parimal

    2013-01-01

    PRIP-Interacting protein with methyl transferase domain (PIMT) serves as a molecular bridge between CREB-binding protein (CBP)/ E1A binding protein p300 (Ep300) -anchored histone acetyl transferase and the Mediator complex sub-unit1 (Med1) and modulates nuclear receptor transcription. Here, we report that ERK2 phosphorylates PIMT at Ser(298) and enhances its ability to activate PEPCK promoter. We observed that PIMT is recruited to PEPCK promoter and adenoviral-mediated over-expression of PIMT in rat primary hepatocytes up-regulated expression of gluconeogenic genes including PEPCK. Reporter experiments with phosphomimetic PIMT mutant (PIMT(S298D)) suggested that conformational change may play an important role in PIMT-dependent PEPCK promoter activity. Overexpression of PIMT and Med1 together augmented hepatic glucose output in an additive manner. Importantly, expression of gluconeogenic genes and hepatic glucose output were suppressed in isolated liver specific PIMT knockout mouse hepatocytes. Furthermore, consistent with reporter experiments, PIMT(S298D) but not PIMT(S298A) augmented hepatic glucose output via up-regulating the expression of gluconeogenic genes. Pharmacological blockade of MAPK/ERK pathway using U0126, abolished PIMT/Med1-dependent gluconeogenic program leading to reduced hepatic glucose output. Further, systemic administration of T4 hormone to rats activated ERK1/2 resulting in enhanced PIMT ser(298) phosphorylation. Phosphorylation of PIMT led to its increased binding to the PEPCK promoter, increased PEPCK expression and induction of gluconeogenesis in liver. Thus, ERK2-mediated phosphorylation of PIMT at Ser(298) is essential in hepatic gluconeogenesis, demonstrating an important role of PIMT in the pathogenesis of hyperglycemia.

  11. ERK2-mediated phosphorylation of transcriptional coactivator binding protein PIMT/NCoA6IP at Ser298 augments hepatic gluconeogenesis.

    Directory of Open Access Journals (Sweden)

    Bandish Kapadia

    Full Text Available PRIP-Interacting protein with methyl transferase domain (PIMT serves as a molecular bridge between CREB-binding protein (CBP/ E1A binding protein p300 (Ep300 -anchored histone acetyl transferase and the Mediator complex sub-unit1 (Med1 and modulates nuclear receptor transcription. Here, we report that ERK2 phosphorylates PIMT at Ser(298 and enhances its ability to activate PEPCK promoter. We observed that PIMT is recruited to PEPCK promoter and adenoviral-mediated over-expression of PIMT in rat primary hepatocytes up-regulated expression of gluconeogenic genes including PEPCK. Reporter experiments with phosphomimetic PIMT mutant (PIMT(S298D suggested that conformational change may play an important role in PIMT-dependent PEPCK promoter activity. Overexpression of PIMT and Med1 together augmented hepatic glucose output in an additive manner. Importantly, expression of gluconeogenic genes and hepatic glucose output were suppressed in isolated liver specific PIMT knockout mouse hepatocytes. Furthermore, consistent with reporter experiments, PIMT(S298D but not PIMT(S298A augmented hepatic glucose output via up-regulating the expression of gluconeogenic genes. Pharmacological blockade of MAPK/ERK pathway using U0126, abolished PIMT/Med1-dependent gluconeogenic program leading to reduced hepatic glucose output. Further, systemic administration of T4 hormone to rats activated ERK1/2 resulting in enhanced PIMT ser(298 phosphorylation. Phosphorylation of PIMT led to its increased binding to the PEPCK promoter, increased PEPCK expression and induction of gluconeogenesis in liver. Thus, ERK2-mediated phosphorylation of PIMT at Ser(298 is essential in hepatic gluconeogenesis, demonstrating an important role of PIMT in the pathogenesis of hyperglycemia.

  12. Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action

    OpenAIRE

    KIMURA, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime

    2013-01-01

    Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA le...

  13. Androgen Receptor-Mediated Genomic Androgen Action Augments Ischemia-Induced Neovascularization.

    Science.gov (United States)

    Lam, Yuen Ting; Lecce, Laura; Tan, Joanne T M; Bursill, Christina A; Handelsman, David J; Ng, Martin K C

    2016-12-01

    Increasing evidence indicates that androgens regulate ischemia-induced neovascularization. However, the role of genomic androgen action mediated by androgen receptor (AR), a ligand-activated nuclear transcription factor, remains poorly understood. Using an AR knockout (KO) mouse strain that contains a transcriptionally inactive AR (AR(Δex3)KO), we examined the role of AR genomic function in modulating androgen-mediated augmentation of ischemia-induced neovascularization. Castrated wild-type (AR(WT)) and AR(Δex3)KO mice were implanted with 5α-dihydrotestosterone (DHT) or placebo pellets after hindlimb ischemia (HLI). DHT modulation of angiogenesis and vasculogenesis, key processes for vascular repair and regeneration, was examined. Laser Doppler perfusion imaging revealed that DHT enhanced blood flow recovery in AR(WT) mice post-HLI. In AR(WT) mice, DHT enhanced angiogenesis by down-regulating prolyl hydroxylase 2 and augmenting hypoxia-inducible factor-1α (HIF-1α) levels in the ischemic tissues post-HLI. DHT also enhanced the production and mobilization of Sca1+/CXCR4+ progenitor cells in the bone marrow (BM) and circulating blood, respectively, in AR(WT) mice. By contrast, DHT-mediated enhancement of blood flow recovery was abrogated in AR(Δex3)KO mice. DHT modulation of HIF-1α expression was attenuated in AR(Δex3)KO mice. DHT-induced HIF-1α transcriptional activity and DHT-augmented paracrine-mediated endothelial cell tubule formation were attenuated in fibroblasts isolated from AR(Δex3)KO mice in vitro. Furthermore, DHT-induced augmentation of Sca1+/CXCR4+ progenitor cell production and mobilization was absent in AR(Δex3)KO mice post-HLI. BM transplantation revealed that ischemia-induced mobilization of circulating progenitor cells was abolished in recipients of AR(Δex3)KO BM. Together, these results indicate that androgen-mediated augmentation of ischemia-induced neovascularization is dependent on genomic AR transcriptional activation.

  14. Ethanolic extract of Allium cepa stimulates glucose transporter typ 4-mediated glucose uptake by the activation of insulin signaling.

    Science.gov (United States)

    Gautam, Sudeep; Pal, Savita; Maurya, Rakesh; Srivastava, Arvind K

    2015-02-01

    The present work was undertaken to investigate the effects and the molecular mechanism of the standardized ethanolic extract of Allium cepa (onion) on the glucose transport for controlling diabetes mellitus. A. cepa stimulates glucose uptake by the rat skeletal muscle cells (L6 myotubes) in both time- and dose-dependent manners. This effect was shown to be mediated by the increased translocation of glucose transporter typ 4 protein from the cytoplasm to the plasma membrane as well as the synthesis of glucose transporter typ 4 protein. The effect of A. cepa extract on glucose transport was stymied by wortmannin, genistein, and AI½. In vitro phosphorylation analysis revealed that, like insulin, A. cepa extract also enhances the tyrosine phosphorylation of the insulin receptor-β, insulin receptor substrate-1, and the serine phosphorylation of Akt under both basal and insulin-stimulated conditions without affecting the total amount of these proteins. Furthermore, it is also shown that the activation of Akt is indispensable for the A. cepa-induced glucose uptake in L6 myotubes. Taken together, these findings provide ample evidence that the ethanolic extract of A. cepa stimulates glucose transporter typ 4 translocation-mediated glucose uptake by the activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt dependent pathway.

  15. Resistant starch and arabinoxylan augment SCFA absorption, but affect postprandial glucose and insulin responses differently - CORRIGENDUM

    DEFF Research Database (Denmark)

    Ingerslev, Anne Krog; Theil, Peter Kappel; Hedemann, Mette Skou;

    2015-01-01

    adaptation to each diet. The pigs were fed a low DF western style control diet (WSD) and two high DF diets; an arabinoxylan (AXD) and a resistant starch (RSD) enriched diet. The NPF of insulin was lower (P = 0.04) in AXD fed pigs (4.6 nmol/h) compared to RSD fed pigs (10.5 nmol/h), despite the lowest NPF......The effects of increased colonic fermentation of dietary fibres (DF) on net portal flux (NPF) of carbohydrate-derived metabolites (glucose, SCFA and especially butyrate), hormones (insulin, C-peptide, GLP-1, GIP) and NEFA were studied in a healthy catheterised pig model. Six 59 ± 3.8 kg pigs were...... of glucose was observed in RSD fed pigs (203 mmol/h, P = 0.02). The NPF of total SCFA, acetate, propionate, and butyrate were high, intermediate, and low (P

  16. Phospholipase D1 mediates AMP-activated protein kinase signaling for glucose uptake.

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    Jong Hyun Kim

    Full Text Available BACKGROUND: Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glucose uptake have yet to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Here, we found that AMPK-induced phospholipase D1 (PLD1 activation is required for (14C-glucose uptake in muscle cells under glucose deprivation conditions. PLD1 activity rather than PLD2 activity is significantly enhanced by glucose deprivation. AMPK-wild type (WT stimulates PLD activity, while AMPK-dominant negative (DN inhibits it. AMPK regulates PLD1 activity through phosphorylation of the Ser-505 and this phosphorylation is increased by the presence of AMP. Furthermore, PLD1-S505Q, a phosphorylation-deficient mutant, shows no changes in activity in response to glucose deprivation and does not show a significant increase in (14C-glucose uptake when compared to PLD1-WT. Taken together, these results suggest that phosphorylation of PLD1 is important for the regulation of (14C-glucose uptake. In addition, extracellular signal-regulated kinase (ERK is stimulated by AMPK-induced PLD1 activation through the formation of phosphatidic acid (PA, which is a product of PLD. An ERK pharmacological inhibitor, PD98059, and the PLD inhibitor, 1-BtOH, both attenuate (14C-glucose uptake in muscle cells. Finally, the extracellular stresses caused by glucose deprivation or aminoimidazole carboxamide ribonucleotide (AICAR; AMPK activator regulate (14C-glucose uptake and cell surface glucose transport (GLUT 4 through ERK stimulation by AMPK-mediated PLD1 activation. CONCLUSIONS/SIGNIFICANCE: These results

  17. Glucose-6-phosphate mediates activation of the carbohydrate responsive binding protein (ChREBP)

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ming V. [Program of Cardiovascular Sciences, Houston, TX 77030 (United States); Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States); Chen, Weiqin [Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States); Harmancey, Romain N. [Division of Cardiology, The University of Texas Health Science Center at Houston, Houston, TX 77030 (United States); Nuotio-Antar, Alli M.; Imamura, Minako; Saha, Pradip [Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States); Taegtmeyer, Heinrich [Division of Cardiology, The University of Texas Health Science Center at Houston, Houston, TX 77030 (United States); Chan, Lawrence, E-mail: lchan@bcm.tmc.edu [Program of Cardiovascular Sciences, Houston, TX 77030 (United States); Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States); St. Luke' s Episcopal Hospital, Houston, TX 77030 (United States)

    2010-05-07

    Carbohydrate response element binding protein (ChREBP) is a Mondo family transcription factor that activates a number of glycolytic and lipogenic genes in response to glucose stimulation. We have previously reported that high glucose can activate the transcriptional activity of ChREBP independent of the protein phosphatase 2A (PP2A)-mediated increase in nuclear entry and DNA binding. Here, we found that formation of glucose-6-phosphate (G-6-P) is essential for glucose activation of ChREBP. The glucose response of GAL4-ChREBP is attenuated by D-mannoheptulose, a potent hexokinase inhibitor, as well as over-expression of glucose-6-phosphatase (G6Pase); kinetics of activation of GAL4-ChREBP can be modified by exogenously expressed GCK. Further metabolism of G-6-P through the two major glucose metabolic pathways, glycolysis and pentose-phosphate pathway, is not required for activation of ChREBP; over-expression of glucose-6-phosphate dehydrogenase (G6PD) diminishes, whereas RNAi knockdown of the enzyme enhances, the glucose response of GAL4-ChREBP, respectively. Moreover, the glucose analogue 2-deoxyglucose (2-DG), which is phosphorylated by hexokinase, but not further metabolized, effectively upregulates the transcription activity of ChREBP. In addition, over-expression of phosphofructokinase (PFK) 1 and 2, synergistically diminishes the glucose response of GAL4-ChREBP. These multiple lines of evidence support the conclusion that G-6-P mediates the activation of ChREBP.

  18. Adenovirus-mediated transfection with glucose transporter 3 suppresses PC12 cell apoptosis following ischemic injury

    Institute of Scientific and Technical Information of China (English)

    Junliang Li; Xinke Xu; Shanyi Zhang; Meiguang Zheng; Zhonghua Wu; Yinlun Weng; Leping Ouyang; Jian Yu; Fangcheng Li

    2012-01-01

    In this study, we investigated the effects of adenovirus-mediated transfection of PC12 cells with glucose transporter 3 after ischemic injury. The results of flow cytometry and TUNEL showed that exogenous glucose transporter 3 significantly suppressed PC12 cell apoptosis induced by ischemic injury. The results of isotopic scintiscan and western blot assays showed that, the glucose uptake rate was significantly increased and nuclear factor kappaB expression was significantly decreased after adenovirus-mediated transfection of ischemic PC12 cells with glucose transporter 3. These results suggest that adenovirus-mediated transfection of cells with glucose transporter 3 elevates the energy metabolism of PC12 cells with ischemic injury, and inhibits cell apoptosis.

  19. High glucose-mediated oxidative stress impairs cell migration.

    Directory of Open Access Journals (Sweden)

    Marcelo L Lamers

    Full Text Available Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we evaluate the hypothesis that high glucose concentrations inhibit cell migration. Using CHO.K1 cells, NIH-3T3 fibroblasts, mouse embryonic fibroblasts and primary skin fibroblasts from control and diabetic rats cultured in 5 mM D-glucose (low glucose, LG, 25 mM D-glucose (high glucose, HG or 25 mM L-glucose medium (osmotic control--OC, we analyzed the migration speed, protrusion stability, cell polarity, adhesion maturation and the activity of the small Rho GTPase Rac1. We also analyzed the effects of reactive oxygen species by incubating cells with the antioxidant N-Acetyl-Cysteine (NAC. We observed that HG conditions inhibited cell migration when compared to LG or OC. This inhibition resulted from impaired cell polarity, protrusion destabilization and inhibition of adhesion maturation. Conversely, Rac1 activity, which promotes protrusion and blocks adhesion maturation, was increased in HG conditions, thus providing a mechanistic basis for the HG phenotype. Most of the HG effects were partially or completely rescued by treatment with NAC. These findings demonstrate that HG impairs cell migration due to an increase in oxidative stress that causes polarity loss, deficient adhesion and protrusion. These alterations arise, in large part, from increased Rac1 activity and may contribute to the poor wound healing observed in diabetic patients.

  20. Brachial Artery Flow-mediated Dilation Following Exercise with Augmented Oscillatory and Retrograde Shear Rate

    Directory of Open Access Journals (Sweden)

    Johnson Blair D

    2012-08-01

    Full Text Available Abstract Background Acute doses of elevated retrograde shear rate (SR appear to be detrimental to endothelial function in resting humans. However, retrograde shear increases during moderate intensity exercise which also enhances post-exercise endothelial function. Since SR patterns differ with the modality of exercise, it is important to determine if augmented retrograde SR during exercise influences post-exercise endothelial function. This study tested the hypothesis that (1 increased doses of retrograde SR in the brachial artery during lower body supine cycle ergometer exercise would attenuate post-exercise flow-mediated dilation (FMD in a dose-dependent manner, and (2 antioxidant vitamin C supplementation would prevent the attenuated post-exercise FMD response. Methods Twelve men participated in four randomized exercise sessions (90 W for 20 minutes on separate days. During three of the sessions, one arm was subjected to increased oscillatory and retrograde SR using three different forearm cuff pressures (20, 40, 60 mmHg (contralateral arm served as the control and subjects ingested placebo capsules prior to exercise. A fourth session with 60 mmHg cuff pressure was performed with 1 g of vitamin C ingested prior to the session. Results Post-exercise FMD following the placebo conditions were lower in the cuffed arm versus the control arm (arm main effect: P P > 0.05. Following vitamin C treatment, post-exercise FMD in the cuffed and control arm increased from baseline (P P > 0.05. Conclusions These results indicate that augmented oscillatory and retrograde SR in non-working limbs during lower body exercise attenuates post-exercise FMD without an evident dose–response in the range of cuff pressures evaluated. Vitamin C supplementation prevented the attenuation of FMD following exercise with augmented oscillatory and retrograde SR suggesting that oxidative stress contributes to the adverse effects of oscillatory and

  1. Neuronal GLP1R mediates liraglutide’s anorectic but not glucose-lowering effect

    OpenAIRE

    Sisley, Stephanie; Gutierrez-Aguilar, Ruth; Scott, Michael; D’Alessio, David A.; Sandoval, Darleen A.; Seeley, Randy J

    2014-01-01

    Glucose control and weight loss are cornerstones of type 2 diabetes treatment. Currently, only glucagon-like peptide-1 (GLP1) analogs are able to achieve both weight loss and glucose tolerance. Both glucose and body weight are regulated by the brain, which contains GLP1 receptors (GLP1R). Even though the brain is poised to mediate the effects of GLP1 analogs, it remains unclear whether the glucose- and body weight–lowering effects of long-acting GLP1R agonists are via direct action on CNS GLP...

  2. Converting enzyme inhibitor temocaprilat prevents high glucose-mediated suppression of human aortic endothelial cell proliferation.

    Science.gov (United States)

    Yasunari, Kenichi; Maeda, Kensaku; Watanabe, Takanori; Nakamura, Munehiro; Asada, Akira; Yoshikawa, Junichi

    2003-12-01

    We examined the involvement of the oxidative stress in high glucose-induced suppression of human aortic endothelial cell proliferation. Chronic glucose treatment for 72 h concentration-dependently (5.6-22.2 mol/l) inhibited human coronary endothelial cell proliferation. Temocaprilat, an angiotensin-converting enzyme inhibitor, at 10 nmol/l to 1 micromol/l inhibited high glucose (22.2 mmol/l)-mediated suppression of human aortic endothelial cell proliferation. Temocaprilat at 1 micromol/l inhibited high glucose-induced membrane-bound protein kinase C activity in human aortic endothelial cells. The protein kinase C inhibitors calphostin C 100 nmol/l or chelerythrine 1 micromol/l inhibited high glucose-mediated suppression of human aortic endothelial cell proliferation. Chronic high glucose treatment for 72 h increased intracellular oxidative stress, directly measured by flow cytometry using carboxydichlorofluorescein diacetate bis-acetoxymethyl ester, and this increase was significantly suppressed by temocaprilat 10 nmol/l to 1 micromol/l. Bradykinin B2 receptor antagonist icatibant 100 nmol/l significantly reduced the action of temocaprilat; whereas bradykinin B1 receptor antagonist des-Arg9-Leu8-bradykinin 100 nmol/l had no effect. These findings suggest that high glucose inhibits human aortic endothelial cell proliferation and that the angiotensin-converting enzyme inhibitor temocaprilat inhibits high glucose-mediated suppression of human aortic endothelial cell proliferation, possibly through suppression of protein kinase C, bradykinin B2 receptors and oxidative stress.

  3. Glucose oxidase-mediated gelation: a simple test to detect glucose in food products.

    Science.gov (United States)

    Liu, Yi; Javvaji, Vishal; Raghavan, Srinivasa R; Bentley, William E; Payne, Gregory F

    2012-09-12

    This paper reports a simple, rapid, and sugar-selective method to induce gelation from glucose-containing samples. This method employs glucose oxidase (GOx) to selectively "recognize" and oxidize glucose to generate gluconic acid, which acts to solubilize calcium carbonate and release calcium ions. The release of calcium ions triggers gelation of the calcium-responsive polysaccharide alginate to form a calcium-alginate hydrogel. Rheological measurements confirm that gel formation is triggered by glucose but not fructose or sucrose (consistent with GOx's selectivity). Vial inversion tests demonstrate that gel formation can be readily observed without the need for instrumentation. Proof-of-concept studies demonstrate that this gel-forming method can detect glucose in food/beverage products sweetened with glucose or high-fructose corn syrups. These results indicate that the enzyme-induced gelation of alginate may provide a simple means to test for sweeteners using components that are safe for use on-site or in the home.

  4. Glucose-responsive artificial promoter-mediated insulin gene transfer improves glucose control in diabetic mice

    Institute of Scientific and Technical Information of China (English)

    Jaeseok Han; Eung-Hwi Kim; Woohyuk Choi; Hee-Sook Jun

    2012-01-01

    AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes.We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter (rAd-SP-rINSfur) into diabetic Leprdb/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control (rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 d.Glucose and insulin tolerance tests were performed.Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic.Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve (AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk (AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice (AUC:9150.17±1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.

  5. Aldose reductase inhibitor improves insulin-mediated glucose uptake and prevents migration of human coronary artery smooth muscle cells induced by high glucose.

    Science.gov (United States)

    Yasunari, K; Kohno, M; Kano, H; Minami, M; Yoshikawa, J

    2000-05-01

    We examined involvement of the polyol pathway in high glucose-induced human coronary artery smooth muscle cell (SMC) migration using Boyden's chamber method. Chronic glucose treatment for 72 hours potentiated, in a concentration-dependent manner (5.6 to 22.2 mol/L), platelet-derived growth factor (PDGF) BB-mediated SMC migration. This potentiation was accompanied by an increase in PDGF BB binding, because of an increased number of PDGF-beta receptors, and this potentiation was blocked by the aldose reductase inhibitor epalrestat. Epalrestat at concentrations of 10 and 100 nmol/L inhibited high glucose-potentiated (22.2 mmol/L), PDGF BB-mediated migration. Epalrestat at 100 nmol/L inhibited a high glucose-induced increase in the reduced/oxidized nicotinamide adenine dinucleotide ratio and membrane-bound protein kinase C (PKC) activity in SMCs. PKC inhibitors calphostin C (100 nmol/L) and chelerythrine (1 micromol/L) each inhibited high glucose-induced, PDGF BB-mediated SMC migration. High glucose-induced suppression of insulin-mediated [(3)H]-deoxyglucose uptake, which was blocked by both calphostin C (100 nmol/L) and chelerythrine (1 micromol/L), was decreased by epalrestat (100 nmol/L). Chronic high glucose treatment for 72 hours increased intracellular oxidative stress, which was directly measured by flow cytometry using carboxydichlorofluorescein diacetate bis-acetoxymethyl ester, and this increase was significantly suppressed by epalrestat (100 nmol/L). Antisense oligonucleotide to PKC-beta isoform inhibited high glucose-mediated changes in SMC migration, insulin-mediated [(3)H]-deoxyglucose uptake, and oxidative stress. These findings suggest that high glucose concentrations potentiate SMC migration in coronary artery and that the aldose reductase inhibitor epalrestat inhibits high glucose-potentiated, PDGF BB-induced SMC migration, possibly through suppression of PKC (PKC-beta), impaired insulin-mediated glucose uptake, and oxidative stress.

  6. Inositol and Phosphatidylinositol Mediated Glucose Derepression, Gene Expression and Invertase Secretion in Yeasts

    Institute of Scientific and Technical Information of China (English)

    Zhen-Ming CHI; Jun-Feng LI; Xiang-Hong WANG; Shu-Min YAO

    2004-01-01

    Glucose repression occurs in many yeast species and some filamentous fungi, and it represses the expression and secretion of many intracellular and extracellular proteins. In recent years, it has been found that many biochemical reactions in yeast cells are mediated by phosphatidylinositol (PI)-type signaling pathway. However, little is known about the relationships between PI-type signaling and glucose repression,gene expression and invertase secretion in yeasts. Many evidences in our previous studies showed that glucose repression, invertase secretion, gene expression and cell growth were mediated by inositol and PI in Saccharomyces and Schizosaccharomyces. The elucidation of the new regulatory mechanisms of protein secretion, gene expression and glucose repression would be an entirely new aspect of inositol and PI-type signaling regulation in yeasts.

  7. High glucose potentiates L-FABP mediated fibrate induction of PPARα in mouse hepatocytes.

    Science.gov (United States)

    Petrescu, Anca D; McIntosh, Avery L; Storey, Stephen M; Huang, Huan; Martin, Gregory G; Landrock, Danilo; Kier, Ann B; Schroeder, Friedhelm

    2013-08-01

    Although liver fatty acid binding protein (L-FABP) binds fibrates and PPARα in vitro and enhances fibrate induction of PPARα in transformed cells, the functional significance of these findings is unclear, especially in normal hepatocytes. Studies with cultured primary mouse hepatocytes show that: 1) At physiological (6mM) glucose, fibrates (bezafibrate, fenofibrate) only weakly activated PPARα transcription of genes in LCFA β-oxidation; 2) High (11-20mM) glucose, but not maltose (osmotic control), significantly potentiated fibrate-induction of mRNA of these and other PPARα target genes to increase LCFA β-oxidation. These effects were associated with fibrate-mediated redistribution of L-FABP into nuclei-an effect prolonged by high glucose-but not with increased de novo fatty acid synthesis from glucose; 3) Potentiation of bezafibrate action by high glucose required an intact L-FABP/PPARα signaling pathway as shown with L-FABP null, PPARα null, PPARα inhibitor-treated WT, or PPARα-specific fenofibrate-treated WT hepatocytes. High glucose alone in the absence of fibrate was ineffective. Thus, high glucose potentiation of PPARα occurred through FABP/PPARα rather than indirectly through other PPARs or glucose induced signaling pathways. These data indicated L-FABP's importance in fibrate-induction of hepatic PPARα LCFA β-oxidative genes, especially in the context of high glucose levels.

  8. All-Plastic Electrochemical Transistor for Glucose Sensing Using a Ferrocene Mediator

    Directory of Open Access Journals (Sweden)

    George G. Malliaras

    2009-12-01

    Full Text Available We demonstrate a glucose sensor based on an organic electrochemical transistor (OECT in which the channel, source, drain, and gate electrodes are made from the conducting polymer poly(3,4-ethylenedioxythiophene doped with poly(styrene sulfonate (PEDOT:PSS. The OECT employs a ferrocene mediator to shuttle electrons between the enzyme glucose oxidase and a PEDOT:PSS gate electrode. The device can be fabricated using a one-layer patterning process and offers glucose detection down to the micromolar range, consistent with levels present in human saliva.

  9. Inhibitory nature of tiagabine-augmented GABAA receptor-mediated depolarizing responses in hippocampal pyramidal cells.

    Science.gov (United States)

    Jackson, M F; Esplin, B; Capek, R

    1999-03-01

    Tiagabine is a potent GABA uptake inhibitor with demonstrated anticonvulsant activity. GABA uptake inhibitors are believed to produce their anticonvulsant effects by prolonging the postsynaptic actions of GABA, released during episodes of neuronal hyperexcitability. However, tiagabine has recently been reported to facilitate the depolarizing actions of GABA in the CNS of adult rats following the stimulation of inhibitory pathways at a frequency (100 Hz) intended to mimic interneuronal activation during epileptiform activity. In the present study, we performed extracellular and whole cell recordings from CA1 pyramidal neurons in rat hippocampal slices to examine the functional consequences of tiagabine-augmented GABA-mediated depolarizing responses. Orthodromic population spikes (PSs), elicited from the stratum radiatum, were inhibited following the activation of recurrent inhibitory pathways by antidromic conditioning stimulation of the alveus, which consisted of either a single stimulus or a train of stimuli delivered at high-frequency (100 Hz, 200 ms). The inhibition of orthodromic PSs produced by high-frequency conditioning stimulation (HFS), which was always of much greater strength and duration than that produced by a single conditioning stimulus, was greatly enhanced following the bath application of tiagabine (2-100 microM). Thus, in the presence of tiagabine (20 microM), orthodromic PSs, evoked 200 and 800 ms following HFS, were inhibited to 7.8 +/- 2.6% (mean +/- SE) and 34.4 +/- 18.5% of their unconditioned amplitudes compared with only 35.4 +/- 12.7% and 98.8 +/- 12.4% in control. Whole cell recordings revealed that the bath application of tiagabine (20 microM) either caused the appearance or greatly enhanced the amplitude of GABA-mediated depolarizing responses (DR). Excitatory postsynaptic potentials (EPSPs) evoked from stratum radiatum at time points that coincided with the DR were inhibited to below the threshold for action-potential firing

  10. Chalcones and Dihydrochalcones Augment TRAIL-Mediated Apoptosis in Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Wojciech Krol

    2010-08-01

    Full Text Available Chalcones and dihydrochalcones exhibit chemopreventive and antitumor activity. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand is a natural endogenous anticancer agent. We examined the cytotoxic and apoptotic effect of chalcones and dihydrochalcones on TRAIL-mediated apoptosis in LNCaP prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was detected using annexin V-FITC by flow cytometry and fluorescence microscopy. The ΔΨm was evaluated using DePsipher staining by fluorescence microscopy. Our study showed that two tested chalcones (chalcone and 2’,6’dihydroxy-4’-methoxychalcone and three dihydrochalcones (2’,6’-dihydroxy-4’4-dimethoxydihydrochalcone, 2’,6’-dihydroxy-4’-methoxydihydro- chalcone,  and 2’,4’,6’-trihydroxydihydrochalcone, called phloretin markedly augmented TRAIL-induced apoptosis and cytotoxicity in LNCaP cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer.

  11. Glucose transporter-8 (GLUT8) mediates glucose intolerance and dyslipidemia in high-fructose diet-fed male mice.

    Science.gov (United States)

    DeBosch, Brian J; Chen, Zhouji; Finck, Brian N; Chi, Maggie; Moley, Kelle H

    2013-11-01

    Members of the glucose transporter (GLUT) family of membrane-spanning hexose transporters are subjects of intensive investigation for their potential as modifiable targets to treat or prevent obesity, metabolic syndrome, and type 2 diabetes mellitus. Mounting evidence suggests that the ubiquitously expressed class III dual-specificity glucose and fructose transporter, GLUT8, has important metabolic homeostatic functions. We therefore tested the hypothesis that GLUT8 mediates the deleterious metabolic effects of chronic high-fructose diet exposure. Here we demonstrate resistance to high-fructose diet-induced glucose intolerance and dyslipidemia concomitant with enhanced oxygen consumption and thermogenesis in GLUT8-deficient male mice. Independent of diet, significantly lower systolic blood pressure both at baseline and after high-fructose diet feeding was also observed by tail-cuff plethysmography in GLUT8-deficient mice vs wild-type controls. Resistance to fructose-induced metabolic dysregulation occurred in the context of enhanced hepatic peroxisome proliferator antigen receptor-γ (PPARγ) protein abundance, whereas in vivo hepatic adenoviral GLUT8 overexpression suppressed hepatic PPARγ expression. Taken together, these findings suggest that GLUT8 blockade prevents fructose-induced metabolic dysregulation, potentially by enhancing hepatic fatty acid metabolism through PPARγ and its downstream targets. We thus establish GLUT8 as a promising target in the prevention of diet-induced obesity, metabolic syndrome, and type 2 diabetes mellitus in males.

  12. LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2.

    Directory of Open Access Journals (Sweden)

    Maryem A Hussein

    Full Text Available High cholesterol and diabetes are major risk factors for atherosclerosis. Regression of atherosclerosis is mediated in part by the Liver X Receptor (LXR through the induction of genes involved in cholesterol transport and efflux. In the context of diabetes, regression of atherosclerosis is impaired. We proposed that changes in glucose levels modulate LXR-dependent gene expression. Using a mouse macrophage cell line (RAW 264.7 and primary bone marrow derived macrophages (BMDMs cultured in normal or diabetes relevant high glucose conditions we found that high glucose inhibits the LXR-dependent expression of ATP-binding cassette transporter A1 (ABCA1, but not ABCG1. To probe for this mechanism, we surveyed the expression of a host of chromatin-modifying enzymes and found that Protein Arginine Methyltransferase 2 (PRMT2 was reduced in high compared to normal glucose conditions. Importantly, ABCA1 expression and ABCA1-mediated cholesterol efflux were reduced in Prmt2-/- compared to wild type BMDMs. Monocytes from diabetic mice also showed decreased expression of Prmt2 compared to non-diabetic counterparts. Thus, PRMT2 represents a glucose-sensitive factor that plays a role in LXR-mediated ABCA1-dependent cholesterol efflux and lends insight to the presence of increased atherosclerosis in diabetic patients.

  13. The MOX promoter in Hansenula polymorpha is ultrasensitive to glucose-mediated carbon catabolite repression.

    Science.gov (United States)

    Dusny, Christian; Schmid, Andreas

    2016-09-01

    Redesigning biology towards specific purposes requires a functional understanding of genetic circuits. We present a quantitative in-depth study on the regulation of the methanol-specific MOX promoter system (PMOX) at the single-cell level. We investigated PMOX regulation in the methylotrophic yeast Hansenula (Ogataea) polymorpha with respect to glucose-mediated carbon catabolite repression. This promoter system is particularly delicate as the glucose as carbon and energy source in turn represses MOX promoter activity. Decoupling single cells from population activity revealed a hitherto underrated ultrasensitivity of the MOX promoter to glucose repression. Environmental control with single-cell technologies enabled quantitative insights into the balance between activation and repression of PMOX with respect to extracellular glucose concentrations. While population-based studies suggested full MOX promoter derepression at extracellular glucose concentrations of ∼1 g L(-1), we showed that glucose-mediated catabolite repression already occurs at concentrations as low as 5 × 10(-4) g L(-1) These findings demonstrate the importance of uncoupling single cells from populations for understanding the mechanisms of promoter regulation in a quantitative manner.

  14. Arctigenin suppresses unfolded protein response and sensitizes glucose deprivation-mediated cytotoxicity of cancer cells.

    Science.gov (United States)

    Sun, Shengrong; Wang, Xiong; Wang, Changhua; Nawaz, Ahmed; Wei, Wen; Li, Juanjuan; Wang, Lijun; Yu, De-Hua

    2011-01-01

    The involvement of unfolded protein response (UPR) activation in tumor survival and resistance to chemotherapies suggests a new anticancer strategy targeting UPR pathway. Arctigenin, a natural product, has been recently identified for its antitumor activity with selective toxicity against cancer cells under glucose starvation with unknown mechanism. Here we found that arctigenin specifically blocks the transcriptional induction of two potential anticancer targets, namely glucose-regulated protein-78 (GRP78) and its analog GRP94, under glucose deprivation, but not by tunicamycin. The activation of other UPR pathways, e.g., XBP-1 and ATF4, by glucose deprivation was also suppressed by arctigenin. A further transgene experiment showed that ectopic expression of GRP78 at least partially rescued arctigenin/glucose starvation-mediated cell growth inhibition, suggesting the causal role of UPR suppression in arctigenin-mediated cytotoxicity under glucose starvation. These observations bring a new insight into the mechanism of action of arctigenin and may lead to the design of new anticancer therapeutics.

  15. Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake.

    Science.gov (United States)

    Beg, Muheeb; Abdullah, Nazish; Thowfeik, Fathima Shazna; Altorki, Nasser K; McGraw, Timothy E

    2017-06-07

    Insulin, downstream of Akt activation, promotes glucose uptake into fat and muscle cells to lower postprandial blood glucose, an enforced change in cellular metabolism to maintain glucose homeostasis. This effect is mediated by the Glut4 glucose transporter. Growth factors also enhance glucose uptake to fuel an anabolic metabolism required for tissue growth and repair. This activity is predominantly mediated by the Glut1. Akt is activated by phosphorylation of its kinase and hydrophobic motif (HM) domains. We show that insulin-stimulated Glut4-mediated glucose uptake requires PDPK1 phosphorylation of the kinase domain but not mTORC2 phosphorylation of the HM domain. Nonetheless, an intact HM domain is required for Glut4-mediated glucose uptake. Whereas, Glut1-mediated glucose uptake also requires mTORC2 phosphorylation of the HM domain, demonstrating both phosphorylation-dependent and independent roles of the HM domain in regulating glucose uptake. Thus, mTORC2 links Akt to the distinct physiologic programs related to Glut4 and Glut1-mediated glucose uptake.

  16. Caffeine's impairment of insulin-mediated glucose disposal cannot be solely attributed to adrenaline in humans

    DEFF Research Database (Denmark)

    Battram, D S; Graham, T E; Dela, F

    2007-01-01

    Caffeine (CAF) impedes insulin-mediated glucose disposal (IMGD) and increases plasma adrenaline concentrations ([ADR]; 0.6 nm). While the antagonism of ADR abolishes the CAF effect, infusion of ADR (0.75 nm) has no effect on IMGD. We have now examined CAF and ADR in concert to determine whether...

  17. TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling

    Directory of Open Access Journals (Sweden)

    Nigel Beaton

    2015-11-01

    Conclusions: Collectively, these findings establish TUSC5 as an adipose tissue-specific protein that enables proper protein recycling, linking the ubiquitous vesicle traffic machinery with tissue-specific insulin-mediated glucose uptake into adipose tissue and the maintenance of a healthy metabolic phenotype in mice and humans.

  18. Glucose uptake mediated by glucose transporter 1 is essential for early tooth morphogenesis and size determination of murine molars.

    Science.gov (United States)

    Ida-Yonemochi, Hiroko; Nakatomi, Mitsushiro; Harada, Hidemitsu; Takata, Hiroki; Baba, Otto; Ohshima, Hayato

    2012-03-01

    Glucose is an essential source of energy for body metabolism and is transported into cells by glucose transporters (GLUTs). Well-characterized class I GLUT is subdivided into GLUTs1-4, which are selectively expressed depending on tissue glucose requirements. However, there is no available data on the role of GLUTs during tooth development. This study aims to clarify the functional significance of class I GLUT during murine tooth development using immunohistochemistry and an in vitro organ culture experiment with an inhibitor of GLUTs1/2, phloretin, and Glut1 and Glut2 short interfering RNA (siRNA). An intense GLUT1-immunoreaction was localized in the enamel organ of bud-stage molar tooth germs, where the active cell proliferation occurred. By the bell stage, the expression of GLUT1 in the dental epithelium was dramatically decreased in intensity, and subsequently began to appear in the stratum intermedium at the late bell stage. On the other hand, GLUT2-immunoreactivity was weakly observed in the whole tooth germs throughout all stages. The inhibition of GLUTs1/2 by phloretin in the bud-stage tooth germs induced the disturbance of primary enamel knot formation, resulting in the developmental arrest of the explants and the squamous metaplasia of dental epithelial cells. Furthermore, the inhibition of GLUTs1/2 in cap-to-bell-stage tooth germs reduced tooth size in a dose dependent manner. These findings suggest that the expression of GLUT1 and GLUT2 in the dental epithelial and mesenchymal cells seems to be precisely and spatiotemporally controlled, and the glucose uptake mediated by GLUT1 plays a crucial role in the early tooth morphogenesis and tooth size determination. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Insulin and non-insulin mediated vasodilation and glucose uptake in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Scheede-Bergdahl, Celena; Olsen, David Benee; Reving, Danny;

    2009-01-01

    AIMS: The objective was to re-examine endothelial function, insulin mediated vasodilation and glucose extraction in the forearm of patients with type 2 diabetes (T2DM) and matched control subjects (CON) to investigate whether blood flow impairments result from diabetes per se or from concurrent...... disease. METHODS: 18 subjects (10 with T2DM, 8 CON) had graded brachial artery infusions of endothelial dependent (acetylcholine: 15, 30, 60mug/min), endothelial independent (sodium nitroprusside: 1, 3, 10mug/min) and partially endothelial mediated (adenosine: 50, 150, 500mug/min) vasodilators....... The protocol was repeated during a hyperinsulinemic clamp. Forearm blood flow and glucose extraction were measured at each dose of vasodilator (with/without insulin). Measurements were also taken in the control arm, reflecting systemic insulin infusion only. RESULTS: Non-insulin mediated increases in bulk...

  20. Antioxidants improve impaired insulin-mediated glucose uptake and prevent migration and proliferation of cultured rabbit coronary smooth muscle cells induced by high glucose.

    Science.gov (United States)

    Yasunari, K; Kohno, M; Kano, H; Yokokawa, K; Minami, M; Yoshikawa, J

    1999-03-16

    To explore the role of intracellular oxidative stress in high glucose-induced atherogenesis, we examined the effect of probucol and/or alpha-tocopherol on the migration and growth characteristics of cultured rabbit coronary vascular smooth muscle cells (VSMCs). Chronic high-glucose-medium (22. 2 mmol/L) treatment increased platelet-derived growth factor (PDGF)-BB-mediated VSMC migration, [3H]thymidine incorporation, and cell number compared with VSMCs treated with normal-glucose medium (5.6 mmol/L+16.6 mmol/L mannose). Probucol and alpha-tocopherol significantly suppressed high glucose-induced increase in VSMC migration, cell number, and [3H]thymidine incorporation. Probucol and alpha-tocopherol suppressed high glucose-induced elevation of the cytosolic ratio of NADH/NAD+, phospholipase D, and membrane-bound protein kinase C activation. Probucol, alpha-tocopherol, and calphostin C improved the high glucose-induced suppression of insulin-mediated [3H]deoxyglucose uptake. Chronic high-glucose treatment increased the oxidative stress, which was significantly suppressed by probucol, alpha-tocopherol, suramin, and calphostin C. These findings suggest that probucol and alpha-tocopherol may suppress high glucose-induced VSMC migration and proliferation via suppression of increases in the cytosolic ratio of free NADH/NAD+, phospholipase D, and protein kinase C activation induced by high glucose, which result in reduction in intracellular oxidative stress.

  1. Glucose availability is a decisive factor for Nrf2-mediated gene expression

    Directory of Open Access Journals (Sweden)

    Elke H. Heiss

    2013-01-01

    Full Text Available Activation of the transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2 is one of the major cellular defense lines against oxidative and xenobiotic stress, but also influences genes involved in lipid and glucose metabolism. It is unresolved whether the cytoprotective and metabolic responses mediated by Nrf2 are connected or separable events in non-malignant cells. In this study we show that activation of Nrf2, either by the small molecule sulforaphane or knockout of the Nrf2 inhibitor Keap1, leads to increased cellular glucose uptake and increased glucose addiction in fibroblasts. Upon Nrf2 activation glucose is preferentially metabolized through the pentose phosphate pathway with increased production of NADPH. Interference with the supply of glucose or the pentose phosphate pathway and NADPH generation not only hampers Nrf2-mediated detoxification of reactive oxygen species on the enzyme level but also Nrf2-initiated expression of antioxidant defense proteins, such as glutathione reductase and heme-oxygenase1. We conclude that the Nrf2-dependent protection against oxidative stress relies on an intact pentose phosphate pathway and that there is crosstalk between metabolism and detoxification already at the level of gene expression in mammalian cells.

  2. Aspirin Augments IgE-Mediated Histamine Release from Human Peripheral Basophils via Syk Kinase Activation

    Directory of Open Access Journals (Sweden)

    Hiroaki Matsuo

    2013-01-01

    Conclusions: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

  3. Exenatide augments first- and second-phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes

    DEFF Research Database (Denmark)

    Fehse, Frauke; Trautmann, Michael; Holst, Jens Juul;

    2005-01-01

    CONTEXT: First-phase insulin secretion (within 10 min after a sudden rise in plasma glucose) is reduced in type 2 diabetes mellitus (DM2). The incretin mimetic exenatide has glucoregulatory activities in DM2, including glucose-dependent enhancement of insulin secretion. OBJECTIVE: The objective o...

  4. A ferrocene-mediated anti-interfering glucose biosensor based on glutin and cellulose acetate

    Institute of Scientific and Technical Information of China (English)

    Wu Baoyan; Li Jing; Shi Haibin; Huang Jiadong; Anzai Jun-ichi; Osa Tetsuo; Chen Qiang

    2006-01-01

    A ferrocene-mediated glucose biosensor removing interference of ascorbic acid and uric acid was developed by coating of ferrocene, glutin and cellulose acetate on screen-printed gold electrode surface. The results show that it can detect glucose sensitively in the presence of uric acid and ascorbic acid, and also suppress the leakage velocity of ferrocene. Compared to the currents of the pretreated electrode, it decreases the current of uric acid and ascorbic acid by 99.4% and 98.8% at 400 mV, respectively, with a dynamic range of 0~30 mM for glucose, sensitivity of 30.73 nA/mM, response time of 10s, and correlation coefficient of 0.998 8.

  5. Effect of PKC on Glucose-Mediated Insulin Secretion in HIT-T15 Cells

    Directory of Open Access Journals (Sweden)

    Akiyoshi H

    2000-09-01

    Full Text Available OBJECTIVE: To clarify the regulation of protein kinase C on glucose-mediated insulin secretion. MAIN OUTCOME MEASURES: We examined the effect of protein kinase C on the cytosolic free Ca(2+ concentration ([Ca(2+]i and the activity of Ca(2+-activated K(+ channels (K(Ca-channel in the insulinoma cell line, HIT-T15. RESULTS: Glucose at a concentration of 10 mmol/L increased the secretion of insulin. This increase was partly inhibited by 1 nmol/L staurosporine, a protein kinase C inhibitor. Staurosporine (1 nmol/L also attenuated the glucose-induced elevations in [Ca(2+]i. On the contrary, glibenclamide (100 nmol/L specifically blocked ATP-sensitive K(+ channels, and increased both [Ca(2+]i and insulin secretion, but staurosporine had no effect on them. Patch clamp studies showed that 10 mmol/L glucose almost completely blocked K(Ca channel activity, an effect that was reversed by 1 nmol/L staurosporine. Phorbol 12-myristate 13-acetate (1 mmol/L, a protein kinase C activator, also decreased K(Ca channel activity. CONCLUSIONS: These results indicate that the activation of protein kinase C is involved in the glucose-induced release of insulin by modulating K(+ channel function in HIT-T15 cells.

  6. Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Koh, Ho-Jin; Toyoda, Taro; Fujii, Nobuharu;

    2010-01-01

    . Whole-body SNARK heterozygotic knockout mice also had impaired contraction-stimulated glucose transport in skeletal muscle, and knockdown of SNARK in C2C12 muscle cells impaired sorbitol-stimulated glucose transport. SNARK is activated by muscle contraction and is a unique mediator of contraction...

  7. Opposite effects of genistein on the regulation of insulin-mediated glucose homeostasis in adipose tissue.

    Science.gov (United States)

    Wang, M; Gao, X J; Zhao, W W; Zhao, W J; Jiang, C H; Huang, F; Kou, J P; Liu, B L; Liu, K

    2013-09-01

    Genistein is an isoflavone phytoestrogen found in a number of plants such as soybeans and there is accumulating evidence that it has beneficial effects on the regulation of glucose homeostasis. In this study we evaluated the effect of genistein on glucose homeostasis and its underlying mechanisms in normal and insulin-resistant conditions. To induce insulin resistance, mice or differentiated 3T3-L1 adipocytes were treated with macrophage-derived conditioned medium. A glucose tolerance test was used to investigate the effect of genistein. Insulin signalling activation, glucose transporter-4 (GLUT4) translocation and AMP-activated PK (AMPK) activation were detected by Western blot analysis or elisa. Genistein impaired glucose tolerance and attenuated insulin sensitivity in normal mice by inhibiting the insulin-induced phosphorylation of insulin receptor substrate-1 (IRS1) at tyrosine residues, leading to inhibition of insulin-mediated GLUT4 translocation in adipocytes. Mac-CM, an inflammatory stimulus induced glucose intolerance accompanied by impaired insulin sensitivity; genistein reversed these changes by restoring the disturbed IRS1 function, leading to an improvement in GLUT4 translocation. In addition, genistein increased AMPK activity under both normal and inflammatory conditions; this was shown to contribute to the anti-inflammatory effect of genistein, which leads to an improvement in insulin signalling and the amelioration of insulin resistance. Genistein showed opposite effects on insulin sensitivity under normal and inflammatory conditions in adipose tissue and this action was derived from its negative or positive regulation of IRS1 function. Its up-regulation of AMPK activity contributes to the inhibition of inflammation implicated in insulin resistance. © 2013 The British Pharmacological Society.

  8. Mitochondrial DNA copy number augments performance of A1C and oral glucose tolerance testing in the prediction of type 2 diabetes

    Science.gov (United States)

    Cho, Seong Beom; Koh, InSong; Nam, Hye-Young; Jeon, Jae-Pil; Lee, Hong Kyu; Han, Bok-Ghee

    2017-01-01

    Here, we tested the performance of the mitochondrial DNA copy number (mtDNA-CN) in predicting future type 2 diabetes (n = 1108). We used the baseline clinical data (age, sex, body mass index, waist-to-hip ratio, systolic and diastolic blood pressure) and the mtDNA-CN, hemoglobin A1c (A1C) levels and results of oral glucose tolerance test (OGTT) including fasting plasma glucose, 1-hour glucose, and 2-hour glucose levels, to predict future diabetes. We built a prediction model using the baseline data and the diabetes status at biannual follow-up of 8 years. The mean area under curve (AUC) for all follow-ups of the full model including all variables was 0.92 ± 0.04 (mean ± standard deviation), while that of the model excluding the mtDNA-CN was 0.90 ± 0.03. The sensitivity of the f4ull model was much greater than that of the model not including mtDNA-CN: the mean sensitivities of the model with and without mtDNA-CN were 0.60 ± 0.06 and 0.53 ± 0.04, respectively. We found that the mtDNA-CN of peripheral leukocytes is a biomarker that augments the predictive power for future diabetes of A1C and OGTT. We believe that these results could provide invaluable information for developing strategies for the management of diabetes. PMID:28251996

  9. Conservation of the Nrf2-Mediated Gene Regulation of Proteasome Subunits and Glucose Metabolism in Zebrafish

    Directory of Open Access Journals (Sweden)

    Vu Thanh Nguyen

    2016-01-01

    Full Text Available The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Besides the exogenous stress response, Nrf2 has been found to regulate numerous cellular functions, including protein turnover and glucose metabolism; however, the evolutionary origins of these functions remain unknown. In the present study, we searched for novel target genes associated with the zebrafish Nrf2 to answer this question. A microarray analysis of zebrafish embryos that overexpressed Nrf2 revealed that 115 candidate genes were targets of Nrf2, including genes encoding proteasome subunits and enzymes involved in glucose metabolism. A real-time quantitative PCR suggested that the expression of 3 proteasome subunits (psma3, psma5, and psmb7 and 2 enzymes involved in glucose metabolism (pgd and fbp1a were regulated by zebrafish Nrf2. We thus next examined the upregulation of these genes by an Nrf2 activator, diethyl maleate, using Nrf2 mutant zebrafish larvae. The results of real-time quantitative PCR and whole-mount in situ hybridization showed that all of these 5 genes were upregulated by diethyl maleate treatment in an Nrf2-dependent manner, especially in the liver. These findings implied that the Nrf2-mediated regulation of the proteasome subunits and glucose metabolism is evolutionarily conserved among vertebrates.

  10. Hypoxia-inducible factor directs POMC gene to mediate hypothalamic glucose sensing and energy balance regulation.

    Science.gov (United States)

    Zhang, Hai; Zhang, Guo; Gonzalez, Frank J; Park, Sung-Min; Cai, Dongsheng

    2011-07-01

    Hypoxia-inducible factor (HIF) is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance.

  11. Hypoxia-inducible factor directs POMC gene to mediate hypothalamic glucose sensing and energy balance regulation.

    Directory of Open Access Journals (Sweden)

    Hai Zhang

    2011-07-01

    Full Text Available Hypoxia-inducible factor (HIF is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance.

  12. Local Augmented Angiotensinogen Secreted from Apoptotic Vascular Endothelial Cells Is a Vital Mediator of Vascular Remodelling.

    Directory of Open Access Journals (Sweden)

    Shyh-Jong Wu

    Full Text Available Vascular remodelling is a critical vasculopathy found in atheromatous diseases and allograft failures. The local renin angiotensin system (RAS has been implicated in vascular remodelling. However, the mechanisms by which the augmented local RAS is associated with the initial event of endothelial cell apoptosis in injured vasculature remain undefined. We induced the apoptosis of human umbilical vein endothelial cells (HUVECs and vascular smooth muscle cells (VSMCs through serum starvation (SS. After the cells were subjected to SS, we found that the mRNA expression of angiotensinogen (AGT was increased by >3-fold in HUVECs and by approximately 2.5-fold in VSMCs. In addition, the expression of angiotensin-converting enzyme (ACE mRNA was increased in VSMCs but decreased to 50% in HUVECs during the same apoptotic process. Increases in the expression of AGT protein and angiotensin II (Ang II were found in a serum-free medium conditioned by HUVECs (SSC. The increased Ang II was suppressed using lisinopril (an ACE inhibitor treatment. Moreover, the activation of ERK1/2 induced by the SSC in VSMCs was also suppressed by losartan. In conclusion, we first demonstrated that the augmented AGT released from apoptotic endothelial cells acts as a vital progenitor of Ang II to accelerate vascular remodelling, and we suggest that blocking local augmented Ang II might be an effective strategy for restraining intimal hyperplasia.

  13. Effects of glucose and insulin on the H9c2 (2-1) cell proliferation may be mediated through regulating glucose transporter 4 expression

    Institute of Scientific and Technical Information of China (English)

    LIU Qian; HUANG Qing-xian; LOU Fu-chen; ZHANG Li; WANG Kun; YU Shan; XU Hua

    2013-01-01

    RNA level in HG1 group was higher on the first day but lower on the second and third day (P <0.05).In HG1,HG2 and HG3 groups,GLUT4 mRNA level had a negative correlation with the level of glucose (P <0.05).GLUT4 mRNA in INSc subgroups was lower than that in INSh subgroups (P <0.05).The expression of GLUT4 protein was similar to that of GLUT4 mRNA.There was a positive correlation between H9c2 cell proliferation and GLUT4 expression (P <0.02).Conclusions Glucose levels could regulate glucose uptake in myocardial cells through influencing GLUT4 expression,and thus affected the cell proliferation and cell function.Insulin levels could affect the myocardial cell function by regulating GLUT4 expression.Effects of glucose and insulin on the myocardial cells proliferation might be mediated through regulating GLUT4 expression.There may be a mechanism of hyperglycemia pre-accommodation (HGPA) in myocardial cells mediated through regulation of GLUT4 expression.

  14. NFAT2 mediates high glucose-induced glomerular podocyte apoptosis through increased Bax expression

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ruizhao, E-mail: liruizhao1979@126.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Zhang, Li, E-mail: Zhanglichangde@163.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Southern Medical University, Guangzhou, Guangdong (China); Shi, Wei, E-mail: shiwei.gd@139.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Zhang, Bin, E-mail: zhangbinyes@yahoo.com.cn [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Liang, Xinling, E-mail: xinlingliang@yahoo.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Liu, Shuangxin, E-mail: mplsxi@yahoo.com.cn [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Wang, Wenjian, E-mail: wwjph@yahoo.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China)

    2013-04-15

    Background: Hyperglycemia promotes podocyte apoptosis and plays a key role in the pathogenesis of diabetic nephropathy. However, the mechanisms that mediate hyperglycemia-induced podocyte apoptosis is still far from being fully understood. Recent studies reported that high glucose activate nuclear factor of activated T cells (NFAT) in vascular smooth muscle or pancreatic β-cells. Here, we sought to determine if hyperglycemia activates NFAT2 in cultured podocyte and whether this leads to podocyte apoptosis. Meanwhile, we also further explore the mechanisms of NFAT2 activation and NFAT2 mediates high glucose-induced podocyte apoptosis. Methods: Immortalized mouse podocytes were cultured in media containing normal glucose (NG), or high glucose (HG) or HG plus cyclosporine A (a pharmacological inhibitor of calcinerin) or 11R-VIVIT (a special inhibitor of NFAT2). The activation of NFAT2 in podocytes was detected by western blotting and immunofluorescence assay. The role of NFAT2 in hyperglycemia-induced podocyte apoptosis was further evaluated by observing the inhibition of NFAT2 activation by 11R-VIVIT using flow cytometer. Intracellular Ca{sup 2+} was monitored in HG-treated podcocytes using Fluo-3/AM. The mRNA and protein expression of apoptosis gene Bax were measured by real time-qPCR and western blotting. Results: HG stimulation activated NFAT2 in a time- and dose-dependent manner in cultured podocytes. Pretreatment with cyclosporine A (500 nM) or 11R-VIVIT (100 nM) completely blocked NFAT2 nuclear accumulation. Meanwhile, the apoptosis effects induced by HG were also abrogated by concomitant treatment with 11R-VIVIT in cultured podocytes. We further found that HG also increased [Ca{sup 2+}]i, leading to activation of calcineurin, and subsequent increased nuclear accumulation of NFAT2 and Bax expression in cultured podocytes. Conclusion: Our results identify a new finding that HG-induced podocyte apoptosis is mediated by calcineurin/NFAT2/Bax signaling pathway

  15. Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells.

    OpenAIRE

    Kontny, U.; Kurane, I; Ennis, F A

    1988-01-01

    It has been reported that anti-dengue antibodies at subneutralizing concentrations augment dengue virus infection of monocytic cells. This is due to the increased uptake of dengue virus in the form of virus-antibody complexes by cells via Fc gamma receptors. We analyzed the effects of recombinant human gamma interferon (rIFN-gamma) on dengue virus infection of human monocytic cells. U937 cells, a human monocytic cell line, were infected with dengue virus in the form of virus-antibody complexe...

  16. Continuous glucose monitoring microsensor with a nanoscale conducting matrix and redox mediator

    Science.gov (United States)

    Pesantez, Daniel

    vitro testing for glucose shows increasing current with increasing analyte concentration. Testing the glucose microsensor with known concentrations of glucose over a period of 48 hours demonstrated both the potential durability and sensitivity of the device. Unknown/blind in vitro glucose experiments showed the reproducibility and accuracy of the microsensor to detect various glucose levels. Thinner polymer matrix films lead to better sensing performance during in vitro tests (0.6nA/mM lower limit sensitivity and 0.2nA/mM upper limit sensitivity). In vitro experiments using electroactive ascorbic acid (AA) and uric acid (UA) showed the selectivity of the sensor for glucose. In an effort to reduce the sensor's oxidation potential (0.7V) and noise, a second generation electron transfer approach was developed by incorporating into a modified Platinum WE with a nanoscale PPy and GOx matrix, a redox mediator. Ferrocene (Fc) was selected as the artificial electron carrier, substituting molecular oxygen in the enzymatic reaction. The incorporation of Fc into the polymer matrix is done by a simple electrochemical synthesis. Modifications in the microsensor design, materials and fabrication process are presented. Experiments with the new sensor generation resulted in higher sensitivity values (22.8nA/mM lower limit sensitivity and 12.5nA/mM upper limit sensitivity) for glucose and noise was further eliminated by operating the sensor at a lower oxidation potential (0.3V). The final experimental work consisted of preliminary ex vivo tests with the MetaSense microdevice on bovine kidney samples, which showed a qualitatively correlation between glucose consumption trend profile during preservation and viability histology outcome.

  17. Induced Treg Cells Augment the Th17-Mediated Intestinal Inflammatory Response in a CTLA4-Dependent Manner.

    Directory of Open Access Journals (Sweden)

    Nobumasa Watanabe

    Full Text Available Th17 cells and Foxp3+ regulatory T cells (Tregs are thought to promote and suppress inflammatory responses, respectively. However, whether they counteract each other or synergize in regulating immune reactions remains controversial. To determine their interactions, we describe the results of experiments employing mouse models of intestinal inflammation by transferring antigen-specific Th cells (Th1, Th2, and Th17 differentiated in vitro followed by the administration of the cognate antigen via enema. We show that cotransfer of induced Tregs (iTregs suppressed Th1- and Th2-mediated colon inflammation. In contrast, colon inflammation induced by transfer of Th17 cells, was augmented by the cotransfer of iTregs. Furthermore, oral delivery of antigen potentiated Th17-mediated colon inflammation. Administration of a blocking antibody against cytotoxic T lymphocyte-associated antigen 4 (CTLA4 abrogated the effects of cotransfer of iTregs, while the injection of a soluble recombinant immunoglobulin (Ig fusion protein, CTLA4-Ig substituted for the cotransfer of iTregs. These results suggest that antigen-specific activation of iTregs in a local environment stimulates the Th17-mediated inflammatory response in a CTLA4-dependent manner.

  18. Ramadan fasting in diabetes patients on insulin pump therapy augmented by continuous glucose monitoring: an observational real-life study.

    Science.gov (United States)

    Khalil, Ali Bernard; Beshyah, Salem A; Abu Awad, Samar M; Benbarka, Mahmoud M; Haddad, Marcil; Al-Hassan, Dana; Kahwatih, Marwa; Nagelkerke, Nico

    2012-09-01

    Hypoglycemia during the daytime of Ramadan fasting is the most feared complication of diabetes. Insulin pump therapy has been proposed as the ideal "theoretical" method for insulin delivery. We report a prospective observational, single-center study of insulin-treated patients using insulin pump therapy during Ramadan 2011. Twenty-one patients (10 males and 11 females) were selected; median age was 26 years. They adjusted their insulin as per their usual practices. Outcome measures obtained before and during Ramadan included body weight, glycosylated hemoglobin, blood glucose, total insulin dose differences, overriding tendency, suspension time during fasting, and number of hypoglycemic episodes. The patients fasted for a median of 29 days. The observed changes during Ramadan were overall not significant quantitatively, but some trends were noted. The total insulin administered during Ramadan was not different from that in the pre-Ramadan period, but there was a redistribution of insulin over a 24-h period in relation to the changes in the daily lifestyle and eating patterns. Basal insulin was decreased during the daytime by 5-20% from before Ramadan and increased during the nighttime. The mean change in the overall amount of basal insulin was not significant. A larger than usual amount of insulin bolus was given at the meals Iftar, Fowala, and Suhur; the change in the total amount of bolus insulin as a percentage change from total insulin was also not significant. No major hypoglycemic episodes were reported. Minor hypoglcemic episodes were equally distributed between daytime and nighttime and were managed by either basal insulin adjustment or suspension from the pump. This study confirms the advantages provided by insulin pump use in patients with diabetes were enhanced by the use of continuous glucose monitoring. We provided more evidence-based advice on how best to adjust the insulin pump during fasting.

  19. Atg7 Knockdown Augments Concanavalin A-Induced Acute Hepatitis through an ROS-Mediated p38/MAPK Pathway.

    Directory of Open Access Journals (Sweden)

    Yan Zhuang

    Full Text Available Concanavalin A (ConA, a T-cell mitogen that induces acute autoimmune hepatitis, is widely used to model pathophysiological processes of human acute autoimmune liver disease. Although autophagy has been extensively studied in the past decade, little is known about its molecular mechanism underlying the regulation of ConA-induced acute hepatitis. In this study, we used a Cre-conditional atg7 KO mouse to investigate the effects of Atg7-associated autophagy on ConA-induced murine hepatitis. Our results demonstrated that atg7 deficiency in mice enhanced macrophage activation and increased pro-inflammatory cytokines upon ConA stimulation. Atg7 silencing resulted in accumulation of dysfunctional mitochondria, disruption of reactive oxygen species (ROS degradation, and increase in pro-inflammatory cytokines in Raw264.7 cells. p38/MAPK and NF-κB levels were increased upon ConA induction due to Atg7 deficiency. Blocking ROS production inhibited ConA-induced p38/IκB phosphorylation and subsequent intracellular inflammatory responses. Hence, this study demonstrated that atg7 knockout in mice or Atg7 knockdown in cell culture augmented ConA-induced acute hepatitis and related cellular malfunction, indicating protective effects of Atg7 on regulating mitochondrial ROS via a p38/MAPK-mediated pathway. Collectively, our findings reveal that autophagy may attenuate macrophage-mediated inflammatory response to ConA and may be the potential therapeutic targets for acute liver injury.

  20. Insulin Signaling Augments eIF4E-Dependent Nonsense-Mediated mRNA Decay in Mammalian Cells.

    Science.gov (United States)

    Park, Jungyun; Ahn, Seyoung; Jayabalan, Aravinth K; Ohn, Takbum; Koh, Hyun Chul; Hwang, Jungwook

    2016-07-01

    Nonsense-mediated mRNA decay (NMD) modulates the level of mRNA harboring a premature termination codon (PTC) in a translation-dependent manner. Inhibition of translation is known to impair NMD; however, few studies have investigated the correlation between enhanced translation and increased NMD. Here, we demonstrate that insulin signaling events increase translation, leading to an increase in NMD of eIF4E-bound transcripts. We provide evidence that (i) insulin-mediated enhancement of translation augments NMD and rapamycin abrogates this enhancement; (ii) an increase in AKT phosphorylation due to inhibition of PTEN facilitates NMD; (iii) insulin stimulation increases the binding of up-frameshift factor 1 (UPF1), most likely to eIF4E-bound PTC-containing transcripts; and (iv) insulin stimulation induces the colocalization of UPF1 and eIF4E in processing bodies. These results illustrate how extracellular signaling promotes the removal of eIF4E-bound NMD targets.

  1. Acidic environment augments FcεRI-mediated production of IL-6 and IL-13 in mast cells

    Energy Technology Data Exchange (ETDEWEB)

    Kamide, Yosuke, E-mail: m08702012@gunma-u.ac.jp [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi (Japan); Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara (Japan); Ishizuka, Tamotsu [Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Tobo, Masayuki [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Tsurumaki, Hiroaki [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi (Japan); Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Aoki, Haruka; Mogi, Chihiro [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Nakakura, Takashi [Department of Anatomy, Graduate School of Medicine, Teikyo University, Tokyo (Japan); Yatomi, Masakiyo; Ono, Akihiro; Koga, Yasuhiko [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi (Japan); Sato, Koichi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Hisada, Takeshi [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi (Japan); Dobashi, Kunio [Gunma University Graduate School of Health Sciences, Maebashi (Japan); Yamada, Masanobu [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi (Japan); Okajima, Fumikazu [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan)

    2015-08-28

    Although blood pH is maintained in a narrow range of around pH 7.4 in living organisms, inflammatory loci are characterized by acidic conditions. Mast cells tend to reside close to the surface of the body in areas such as the mucosa and skin where they may be exposed to exogenous acids, and they play an important role in immune responses. However, little is known about the effects of extracellular acidification on the functions of mast cell. Here, we found that extracellular acidification increased the dinitrophenyl-conjugated human serum albumin (DNP-HSA)-induced production of interleukin (IL)-6 and IL-13 in MC/9 cells or bone marrow-derived mouse mast cells sensitized with anti-DNP IgE. Extracellular acidification also inhibited migration of MC/9 cells toward DNP-HSA. In addition, acidic pH stimulated antigen-induced activation of p38 mitogen-activated protein kinase (MAPK) and protein kinase B (Akt). These findings suggest that extracellular acidification augmented antigen/IgE-induced and FcεRI-mediated production of IL-6 and IL-13 in mast cells, and that this was associated with the enhancement of p38 MAPK and Akt activation. - Highlights: • Antigen-induced IL-6 and IL-13 production was augmented by acidic pH in mast cells. • Acidic pH-induced actions were associated with activation of p38 MAPK and Akt. • Inhibition of p38 MAPK and Akt attenuated cytokine responses to acidic pH. • Acidic pH effects are not attributable to actions of known proton-sensing GPCRs.

  2. Thioredoxin interacting protein mediates lipid-induced impairment of glucose uptake in skeletal muscle.

    Science.gov (United States)

    Mandala, Ashok; Das, Nabanita; Bhattacharjee, Sudarshan; Mukherjee, Bidisha; Mukhopadhyay, Satinath; Roy, Sib Sankar

    2016-10-28

    Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR. However, the molecular mechanisms behind are unclear. We identified thioredoxin interacting protein (TxNIP), which is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake. FFA-induced overexpression of TxNIP gene was mediated through the activation of its bona-fide trans activator, ChREBP. Further, Palmitate-induced impairment in AMPK-SIRT-1 pathway resulted in overexpression of ChREBP. While Fenofibrate, abrogated PA-induced TxNIP expression and ROS generation in skeletal muscle cells, Saroglitazar, a dual PPARα/γ-agonist, not only inhibited PA-induced TXNIP expression but also led to greater improvement in glucose uptake. Taken together, TxNIP appears to be an important factor in FFA-induced ROS generation and IR in skeletal muscle cells, which can be modulated for the management of this complex disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport.

    Science.gov (United States)

    Nagarajan, Arvindhan; Dogra, Shaillay Kumar; Sun, Lisha; Gandotra, Neeru; Ho, Thuy; Cai, Guoping; Cline, Gary; Kumar, Priti; Cowles, Robert A; Wajapeyee, Narendra

    2017-08-17

    Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via stomatin. The loss of PON2 initiates the cellular starvation response and activates AMP-activated protein kinase (AMPK). In turn, AMPK activates FOXO3A and its transcriptional target, PUMA, which induces anoikis to suppress PDAC tumor growth and metastasis. Pharmacological or genetic activation of AMPK, similar to PON2 inhibition, blocks PDAC tumor growth. Collectively, our results identify PON2 as a new modulator of glucose transport that regulates a pharmacologically tractable pathway necessary for PDAC tumor growth and metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Ghrelin Facilitates GLUT2-, SGLT1- and SGLT2-mediated Intestinal Glucose Transport in Goldfish (Carassius auratus)

    Science.gov (United States)

    Blanco, Ayelén Melisa; Bertucci, Juan Ignacio; Ramesh, Naresh; Delgado, María Jesús; Valenciano, Ana Isabel; Unniappan, Suraj

    2017-01-01

    Glucose homeostasis is an important biological process that involves a variety of regulatory mechanisms. This study aimed to determine whether ghrelin, a multifunctional gut-brain hormone, modulates intestinal glucose transport in goldfish (Carassius auratus). Three intestinal glucose transporters, the facilitative glucose transporter 2 (GLUT2), and the sodium/glucose co-transporters 1 (SGLT1) and 2 (SGLT2), were studied. Immunostaining of intestinal sections found colocalization of ghrelin and GLUT2 and SGLT2 in mucosal cells. Some cells containing GLUT2, SGLT1 and SGLT2 coexpressed the ghrelin/growth hormone secretagogue receptor 1a (GHS-R1a). Intraperitoneal glucose administration led to a significant increase in serum ghrelin levels, as well as an upregulation of intestinal preproghrelin, ghrelin O-acyltransferase and ghs-r1 expression. In vivo and in vitro ghrelin treatment caused a concentration- and time-dependent modulation (mainly stimulatory) of GLUT2, SGLT1 and SGLT2. These effects were abolished by the GHS-R1a antagonist [D-Lys3]-GHRP-6 and the phospholipase C inhibitor U73122, suggesting that ghrelin actions on glucose transporters are mediated by GHS-R1a via the PLC/PKC signaling pathway. Finally, ghrelin stimulated the translocation of GLUT2 into the plasma membrane of goldfish primary intestinal cells. Overall, data reported here indicate an important role for ghrelin in the modulation of glucoregulatory machinery and glucose homeostasis in fish. PMID:28338019

  5. Protective role of morin, a flavonoid, against high glucose induced oxidative stress mediated apoptosis in primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Radhika Kapoor

    Full Text Available Apoptosis is an early event of liver damage in diabetes and oxidative stress has been linked to accelerate the apoptosis in hepatocytes. Therefore, the compounds that can scavenge ROS may confer regulatory effects on high-glucose induced apoptosis. In the present study, primary rat hepatocytes were exposed to high concentration (40 mM of glucose. At this concentration decreased cell viability and enhanced ROS generation was observed. Depleted antioxidant status of hepatocytes under high glucose stress was also observed as evident from transcriptional level and activities of antioxidant enzymes. Further, mitochondrial depolarisation was accompanied by the loss of mitochondrial integrity and altered expression of Bax and Bcl-2. Increased translocation of apoptotic proteins like AIF (Apoptosis inducing factor & Endo-G (endonuclease-G from its resident place mitochondria to nucleus was also observed. Cyt-c residing in the inter-membrane space of mitochondria also translocated to cytoplasm. These apoptotic proteins initiated caspase activation, DNA fragmentation, chromatin condensation, increased apoptotic DNA content in glucose treated hepatocytes, suggesting mitochondria mediated apoptotic mode of cell death. Morin, a dietary flavonoid from Psidium guajava was effective in increasing the cell viability and decreasing the ROS level. It maintained mitochondrial integrity, inhibited release of apoptotic proteins from mitochondria, prevented DNA fragmentation, chromatin condensation and hypodiploid DNA upon exposure to high glucose. This study confirms the capacity of dietary flavonoid Morin in regulating apoptosis induced by high glucose via mitochondrial mediated pathway through intervention of oxidative stress.

  6. AUGMENTATIVE EFFECT OF PROSTAGLANDIN E1 ON PENTOBARBITAL HYPNOSIS MEDIATED BY 5-HT IN CHICKS

    Directory of Open Access Journals (Sweden)

    Amalendu Chanda

    2012-01-01

    Full Text Available Prostaglandins (PG are present in different tissues specially in brain tissues endowed with different central nervous system activities. Similarly, 5-hydroxytryptamine (5-HT a biogenic amine with its presence in different central and peripheral tissues as neurotransmitter plays an important role in the regulation of physiological functions specially hypnosis, convulsions, analgesia in rats, mice, cats and chicks etc. Pentobarbitone (PB induced sleep appear to be a serotonergic modulator activity in different animals. PGE1 potentiates the pentobarbitone hypnosis also mediated through serotonin. In the present study, PGE1 induced sleeping time in chicks was evaluated. Drugs affecting 5-HT synthesis, metabolism and receptor activity modulate the potentiating response, while adrenergic receptor antagonists did not showed any response. This study suggest that PGE1 potentiate PB induced sleep through serotonergic signaling pathway as PGE1 increased 5-HT synthesis rate in chick brain.

  7. Expression of the human isoform of glutamate dehydrogenase, hGDH2, augments TCA cycle capacity and oxidative metabolism of glutamate during glucose deprivation in astrocytes.

    Science.gov (United States)

    Nissen, Jakob D; Lykke, Kasper; Bryk, Jaroslaw; Stridh, Malin H; Zaganas, Ioannis; Skytt, Dorte M; Schousboe, Arne; Bak, Lasse K; Enard, Wolfgang; Pääbo, Svante; Waagepetersen, Helle S

    2017-03-01

    A key enzyme in brain glutamate homeostasis is glutamate dehydrogenase (GDH) which links carbohydrate and amino acid metabolism mediating glutamate degradation to CO2 and expanding tricarboxylic acid (TCA) cycle capacity with intermediates, i.e. anaplerosis. Humans express two GDH isoforms, GDH1 and 2, whereas most other mammals express only GDH1. hGDH1 is widely expressed in human brain while hGDH2 is confined to astrocytes. The two isoforms display different enzymatic properties and the nature of these supports that hGDH2 expression in astrocytes potentially increases glutamate oxidation and supports the TCA cycle during energy-demanding processes such as high intensity glutamatergic signaling. However, little is known about how expression of hGDH2 affects the handling of glutamate and TCA cycle metabolism in astrocytes. Therefore, we cultured astrocytes from cerebral cortical tissue of hGDH2-expressing transgenic mice. We measured glutamate uptake and metabolism using [(3) H]glutamate, while the effect on metabolic pathways of glutamate and glucose was evaluated by use of (13) C and (14) C substrates and analysis by mass spectrometry and determination of radioactively labeled metabolites including CO2 , respectively. We conclude that hGDH2 expression increases capacity for uptake and oxidative metabolism of glutamate, particularly during increased workload and aglycemia. Additionally, hGDH2 expression increased utilization of branched-chain amino acids (BCAA) during aglycemia and caused a general decrease in oxidative glucose metabolism. We speculate, that expression of hGDH2 allows astrocytes to spare glucose and utilize BCAAs during substrate shortages. These findings support the proposed role of hGDH2 in astrocytes as an important fail-safe during situations of intense glutamatergic activity. GLIA 2017;65:474-488.

  8. Augmentation of transgenic expression by ultrasound‑mediated liposome microbubble destruction.

    Science.gov (United States)

    Chen, Zhi-Yi; Sun, Xiao-Fang; Liu, Jian-Qiao; Si-Tu, Bing; Qiu, Ri-Xiang; Liang, Kun; Liu, Jian-Hua; Liang, Wei-Xiang; Zhou, Xin-Xin; Zhang, Hua; Yu, Jiang-Xiu

    2012-04-01

    Non-invasive, efficient and tissue-specific transgenic technologies could be valuable in gene therapy. Although non-viral carriers may be safer and cheaper, they have a much lower transfection efficiency than viral gene carriers. The present study was designed to test the transgenic expression and safety of red fluorescent protein (RFP) in HeLa cells in vitro and in transplanted tumors of nude mice in vivo under ultrasound-mediated liposome microbubble destruction (UMLMD) conditions. Plasmids containing RFP were gently mixed with liposome microbubbles (LMs). The mixture was added to HeLa cells or injected into BALB/c mice by the tail vein under various ultrasound exposure and LM parameters, and then the transfection efficiencies were examined. The results in vivo and in vitro demonstrated that, following a comparison of the plasmid group, the ultrasound + plasmid group and the LM + plasmid group, UMLMD significantly increased the transgenic expression (P<0.01) without causing any apparent detrimental effect. From the study, we concluded that UMLMD could be a non-invasive, effective and promising non-viral technique for gene therapy and transgenic research.

  9. Dioscin augments HSV-tk-mediated suicide gene therapy for melanoma by promoting connexin-based intercellular communication

    Science.gov (United States)

    Li, Bin; Wu, Yingya; Liu, Xijuan; Tan, Yuhui; Du, Biaoyan

    2017-01-01

    Suicide gene therapy is a promising strategy against melanoma. However, the low efficiency of the gene transfer technique can limit its application. Our preliminary data showed that dioscin, a glucoside saponin, could upregulate the expression of connexins Cx26 and Cx43, major components of gap junctions, in melanoma cells. We hypothesized that dioscin may increase the bystander effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) through increasing the formation of gap junctions. Further analysis showed that dioscin indeed could increase the gap junctional intercellular communication in B16 melanoma cells, resulting in more efficient GCV-induced bystander killing in B16tk cells. By contrast, overexpression of dominant negative Cx43 impaired the cell-cell communication of B16 cells and subsequently weakened the bystander effect of HSV-tk/GCV gene therapy. In vivo, combination treatment with dioscin and GCV of tumor-bearing mice with 30% positive B16tk cells and 70% wild-type B16 cells caused a significant reduction in tumor volume and weight compared to treatment with GCV or dioscin alone. Taken together, these results demonstrated that dioscin could augment the bystander effect of the HSV-tk/GCV system through increasing connexin-mediated gap junction coupling. PMID:27903977

  10. eIF1A augments Ago2-mediated Dicer-independent miRNA biogenesis and RNA interference

    Science.gov (United States)

    Yi, Tingfang; Arthanari, Haribabu; Akabayov, Barak; Song, Huaidong; Papadopoulos, Evangelos; Qi, Hank H.; Jedrychowski, Mark; Güttler, Thomas; Guo, Cuicui; Luna, Rafael E.; Gygi, Steven P.; Huang, Stephen A.; Wagner, Gerhard

    2015-05-01

    MicroRNA (miRNA) biogenesis and miRNA-guided RNA interference (RNAi) are essential for gene expression in eukaryotes. Here we report that translation initiation factor eIF1A directly interacts with Ago2 and promotes Ago2 activities in RNAi and miR-451 biogenesis. Biochemical and NMR analyses demonstrate that eIF1A binds to the MID domain of Ago2 and this interaction does not impair translation initiation. Alanine mutation of the Ago2-facing Lys56 in eIF1A impairs RNAi activities in human cells and zebrafish. The eIF1A-Ago2 assembly facilitates Dicer-independent biogenesis of miR-451, which mediates erythrocyte maturation. Human eIF1A (heIF1A), but not heIF1A(K56A), rescues the erythrocyte maturation delay in eif1axb knockdown zebrafish. Consistently, miR-451 partly compensates erythrocyte maturation defects in zebrafish with eif1axb knockdown and eIF1A(K56A) expression, supporting a role of eIF1A in miRNA-451 biogenesis in this model. Our results suggest that eIF1A is a novel component of the Ago2-centred RNA-induced silencing complexes (RISCs) and augments Ago2-dependent RNAi and miRNA biogenesis.

  11. A mediator-free glucose biosensor based on glucose oxidase/chitosan/α-zirconium phosphate ternary biocomposite.

    Science.gov (United States)

    Liu, Li-Min; Wen, Jiwu; Liu, Lijun; He, Deyong; Kuang, Ren-yun; Shi, Taqing

    2014-01-15

    A novel glucose oxidase/chitosan/α-zirconium phosphate (GOD/chitosan/α-ZrP) ternary biocomposite was prepared by co-intercalating glucose oxidase (GOD) and chitosan into the interlayers of α-zirconium phosphate (α-ZrP) via a delamination-reassembly procedure. The results of X-ray diffraction, infrared spectroscopy, circular dichroism, and ultraviolet spectrum characterizations indicated not only the layered and hybrid structure of the GOD/chitosan/α-ZrP ternary biocomposite but also the recovered activity of the intercalated GOD improved by the co-intercalated chitosan. By depositing the GOD/chitosan/α-ZrP biocomposite film onto a glassy carbon electrode, the direct electrochemistry of the intercalated GOD was achieved with a fast electron transfer rate constant, k(s), of 7.48±3.52 s(-1). Moreover, this GOD/chitosan/α-ZrP biocomposite modified electrode exhibited a sensitive response to glucose in the linear range of 0.25-8.0 mM (R=0.9994, n=14), with a determination limit of 0.076 mM.

  12. Pinitol supplementation does not affect insulin-mediated glucose metabolism and muscle insulin receptor content and phosphorylation in older humans.

    Science.gov (United States)

    Campbell, Wayne W; Haub, Mark D; Fluckey, James D; Ostlund, Richard E; Thyfault, John P; Morse-Carrithers, Hannah; Hulver, Matthew W; Birge, Zonda K

    2004-11-01

    This study assessed the effect of oral pinitol supplementation on oral and intravenous glucose tolerances and on skeletal muscle insulin receptor content and phosphorylation in older people. Fifteen people (6 men, 9 women; age 66 +/- 8 y; BMI 27.9 +/- 3.3 kg/m(2); hemoglobin A1c 5.39 +/- 0.46%, mean +/- SD) completed a 7-wk protocol. Subjects were randomly assigned to groups that during wk 2-7 consumed twice daily either a non-nutritive beverage (Placebo group, n = 8) or the same beverage with 1000 mg pinitol dissolved into it (Pinitol group, n = 7, total dose = 2000 mg pinitol/d). Testing was done at wk 1 and wk 7. In the Pinitol group with supplementation, 24-h urinary pinitol excretion increased 17-fold. The fasting concentrations of glucose, insulin, and C-peptide, and the 180-min area under the curve for these compounds, in response to oral (75 g) and intravenous (300 mg/kg) glucose tolerance challenges, were unchanged from wk 1 to wk 7 and were not influenced by pinitol. Also, pinitol did not affect indices of hepatic and whole-body insulin sensitivity from the oral glucose tolerance test and indices of insulin sensitivity, acute insulin response to glucose, and glucose effectiveness from the intravenous glucose tolerance test, estimated using minimal modeling. Pinitol did not differentially affect total insulin receptor content and insulin receptor phosphotyrosine 1158 and insulin receptor phosphotyrosine 1162/1163 activation in vastus lateralis samples taken during an oral-glucose-induced hyperglycemic and hyperinsulinemic state. These data suggest that pinitol supplementation does not influence whole-body insulin-mediated glucose metabolism and muscle insulin receptor content and phosphorylation in nondiabetic, older people.

  13. Uptake and phloem transport of glucose-fipronil conjugate in Ricinus communis involve a carrier-mediated mechanism.

    Science.gov (United States)

    Wu, Han-Xiang; Yang, Wen; Zhang, Zhi-Xiang; Huang, Ting; Yao, Guang-Kai; Xu, Han-Hong

    2012-06-20

    Some compounds containing glucose are absorbed via the monosaccharide transporters of the plasma membrane. A glucose-fipronil conjugate, N-[3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazol-5-yl]-1-(β-d-glucopyranosyl)-1H-1,2,3-triazole-4-methanamine (GTF), has been synthesized in our previous work. GTF exhibits moderate phloem mobility in Ricinus communis. In the current paper, we demonstrate that the uptake of GTF by Ricinus seedling cotyledon discs is partly mediated by an active carrier system (K(m)1 = 0.17 mM; V(max)1 = 2.2 nmol cm(-2) h(-1)). Four compounds [d-glucose, sucrose, phloridzin, and carbonyl cyanide m-chlorophenylhydrazone (CCCP)] were examined for their effect on GTF uptake. Phloridzin as well as CCCP markedly inhibit GTF uptake, and d-glucose weakly competes with it. The phloem transport of GTF in Ricinus seedlings is found to involve an active carrier-mediated mechanism that effectively contributes to the GTF phloem loading. The results prove that adding a glucose core is a reasonable and feasible approach to confer phloem mobility to fipronil by utilizing plant monosaccharide transporters.

  14. Insulin Mediated 14C-Glucose Incorporation Into Adipose Tissue: An Undergraduate Biochemistry Experiment

    Science.gov (United States)

    Landman, A. D.; Eskin, N. A. M.

    1975-01-01

    Describes an experiment in which rat adipose tissue samples are exposed to labeled glucose; insulin is added to one sample. Subsequent scintillation counting demonstrates the ability of insulin to facilitate the entry of glucose into the tissue. (MLH)

  15. The mitochondrial 2-oxoglutarate carrier is part of a metabolic pathway that mediates glucose- and glutamine-stimulated insulin secretion.

    Science.gov (United States)

    Odegaard, Matthew L; Joseph, Jamie W; Jensen, Mette V; Lu, Danhong; Ilkayeva, Olga; Ronnebaum, Sarah M; Becker, Thomas C; Newgard, Christopher B

    2010-05-28

    Glucose-stimulated insulin secretion from pancreatic islet beta-cells is dependent in part on pyruvate cycling through the pyruvate/isocitrate pathway, which generates cytosolic alpha-ketoglutarate, also known as 2-oxoglutarate (2OG). Here, we have investigated if mitochondrial transport of 2OG through the 2-oxoglutarate carrier (OGC) participates in control of nutrient-stimulated insulin secretion. Suppression of OGC in clonal pancreatic beta-cells (832/13 cells) and isolated rat islets by adenovirus-mediated delivery of small interfering RNA significantly decreased glucose-stimulated insulin secretion. OGC suppression also reduced insulin secretion in response to glutamine plus the glutamate dehydrogenase activator 2-amino-2-norbornane carboxylic acid. Nutrient-stimulated increases in glucose usage, glucose oxidation, glutamine oxidation, or ATP:ADP ratio were not affected by OGC knockdown, whereas suppression of OGC resulted in a significant decrease in the NADPH:NADP(+) ratio during stimulation with glucose but not glutamine + 2-amino-2-norbornane carboxylic acid. Finally, OGC suppression reduced insulin secretion in response to a membrane-permeant 2OG analog, dimethyl-2OG. These data reveal that the OGC is part of a mechanism of fuel-stimulated insulin secretion that is common to glucose, amino acid, and organic acid secretagogues, involving flux through the pyruvate/isocitrate cycling pathway. Although the components of this pathway must remain intact for appropriate stimulus-secretion coupling, production of NADPH does not appear to be the universal second messenger signal generated by these reactions.

  16. Intein-mediated rapid purification of recombinant maxadilan and M65 and their acute effects on plasma glucose

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Maxadilan is a potent vasodilatory peptide present in the sali-vary glands of the sand fly. Maxadilan and M65, a deletion variation of maxadilan, are agonist- and antagonist-specific for the PAC1 receptor. In order to obtain the recombinant maxadilan and M65 efficiently by intein-mediated single col-umn purification, the genes encoding maxadilan and M65 were designed, synthesized and cloned into Escherichia coli expression vector pKYB. The recombinant maxadilan and M65 with homogeneity over 95% were released from the chitin-bound intein tag by β-mercaptoethanol. Intraperitoneal in-jection of the recombinant maxadilan caused an acute eleva-tion of plasma glucose, imitating pituitary adenylate cyclase-activating polypeptide (PACAP) 27, in NIH mice, while the VPACl-agonist and VPAC2-agonist had no significant ef-fects on the levels of plasma glucose. M65 alone had no effect on the plasma glucose, but blocked the glucose excursion caused by maxadilan by 12.7% and blocked the glucose ex-cursion caused by the PACAP 27 by 11.6%. The acute ef-fects of the recombinant maxadilan and M65 on the plasma glucose indicated that they had the characteristics as the agonist and antagonist for PAC1.

  17. BDNF mediates neuroprotection against oxygen-glucose deprivation by the cardiac glycoside oleandrin.

    Science.gov (United States)

    Van Kanegan, Michael J; He, Dong Ning; Dunn, Denise E; Yang, Peiying; Newman, Robert A; West, Anne E; Lo, Donald C

    2014-01-15

    We have previously shown that the botanical drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, provides neuroprotection in both in vitro and in vivo brain slice-based models for focal ischemia (Dunn et al., 2011). Intriguingly, plasma levels of the neurotrophin BDNF were increased in patients treated with PBI-05204 in a phase I clinical trial (Bidyasar et al., 2009). We thus tested the hypothesis that neuroprotection provided by PBI-05204 to rat brain slices damaged by oxygen-glucose deprivation (OGD) is mediated by BDNF. We found, in fact, that exogenous BDNF protein itself is sufficient to protect brain slices against OGD, whereas downstream activation of TrkB receptors for BDNF is necessary for neuroprotection provided by PBI-05204, using three independent methods. Finally, we provide evidence that oleandrin, the principal cardiac glycoside component of PBI-05204, can quantitatively account for regulation of BDNF at both the protein and transcriptional levels. Together, these findings support further investigation of cardiac glycosides in providing neuroprotection in the context of ischemic stroke.

  18. IL-15 Activates the Jak3/STAT3 Signaling Pathway to Mediate Glucose Uptake in Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    James E Krolopp

    2016-12-01

    Full Text Available Myokines are specialized cytokines that are secreted from skeletal muscle (SKM in response to metabolic stimuli, such as exercise. Interleukin-15 (IL-15 is a myokine with potential to reduce obesity and increase lean mass through induction of metabolic processes. It has been previously shown that IL-15 acts to increase glucose uptake in SKM cells. However, the downstream signals orchestrating the link between IL-15 signaling and glucose uptake have not been fully explored. Here we employed the mouse SKM C2C12 cell line to examine potential downstream targets of IL-15-induced alterations in glucose uptake. Following differentiation, C2C12 cells were treated overnight with 100 ng/ml of IL-15. Activation of factors associated with glucose metabolism (Akt and AMPK and known downstream targets of IL-15 (Jak1, Jak3, STAT3, and STAT5 were assessed with IL-15 stimulation. IL-15 stimulated glucose uptake and GLUT4 translocation to the plasma membrane. IL-15 treatment had no effect on phospho-Akt, phospho-Akt substrates, phospho-AMPK, phospho-Jak1, or phospho-STAT5. However, with IL-15, phospho-Jak3 and phospho-STAT3 levels were increased along with increased interaction of Jak3 and STAT3. Additionally, IL-15 induced a translocation of phospho-STAT3 from the cytoplasm to the nucleus. We have evidence that a mediator of glucose uptake, HIF1α, expression was dependent on IL-15 induced STAT3 activation. Finally, upon inhibition of STAT3 the positive effects of IL-15 on glucose uptake and GLUT4 translocation were abolished. Taken together, we provide evidence for a novel signaling pathway for IL-15 acting through Jak3/STAT3 to regulate glucose metabolism.

  19. Water stress augments silicon-mediated resistance of susceptible sugarcane cultivars to the stalk borer Eldana saccharina (Lepidoptera: Pyralidae).

    Science.gov (United States)

    Kvedaras, O L; Keeping, M G; Goebel, F-R; Byrne, M J

    2007-04-01

    Silicon (Si) can improve resistance of plants to insect attack and may also enhance tolerance of water stress. This study tested if Si-mediated host plant resistance to insect attack was augmented by water stress. Four sugarcane cultivars, two resistant (N21, N33) and two susceptible (N26, N11) to Eldana saccharina Walker were grown in a pot trial in Si-deficient river sand, with (Si+) and without (Si-) calcium silicate. To induce water stress, irrigation to half the trial was reduced after 8.5 months. The trial was artificially infested with E. saccharina eggs after water reduction and harvested 66 days later. Silicon treated, stressed and non-stressed plants of the same cultivar did not differ appreciably in Si content. Decreases in numbers of borers recovered and stalk damage were not associated with comparable increases in rind hardness in Si+ cane, particularly in water-stressed susceptible cultivars. Overall, Si+ plants displayed increased resistance to E. saccharina attack compared with Si- plants. Borer recoveries were significantly lower in stressed Si+ cane compared with either stressed Si- or non-stressed Si- and Si+ cane. Generally, fewer borers were recovered from resistant cultivars than susceptible cultivars. Stalk damage was significantly lower in Si+ cane than in Si- cane, for N21, N11 and N26. Stalk damage was significantly less in Si+ combined susceptible cultivars than in Si- combined susceptible cultivars under non-stressed and especially stressed conditions. In general, the reduction in borer numbers and stalk damage in Si+ plants was greater for water-stressed cane than non-stressed cane, particularly for susceptible sugarcane cultivars. The hypothesis that Si affords greater protection against E. saccharina borer attack in water-stressed sugarcane than in non-stressed cane and that this benefit is greatly enhanced in susceptible cultivars is supported. A possible active role for soluble Si in defence against E. saccharina is proposed.

  20. High glucose mediates endothelial-to-chondrocyte transition in human aortic endothelial cells

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    Tang Rining

    2012-09-01

    Full Text Available Abstract Background Vascular calcification is one of the common complications in diabetes mellitus. Many studies have shown that high glucose (HG caused cardiovascular calcification, but its underlying mechanism is not fully understood. Recently, medial calcification has been most commonly described in the vessels of patients with diabetes. Chondrocytes were involved in the medial calcification. Recent studies have shown that the conversion into mesenchymal stem cells (MSCs via the endothelial-to-mesenchymal transition (EndMT could be triggered in chondrocytes. Our previous research has indicated that HG induced EndMT in human aortic endothelial cells (HAECs. Therefore, we addressed the question of whether HG-induced EndMT could be transitioned into MSCs and differentiated into chondrocytes. Methods HAECs were divided into three groups: a normal glucose (NG group, HG group (30 mmol/L, and mannitol (5.5 mmol/L NG + 24.5 mmol/L group. Pathological changes were investigated using fluorescence microscopy and electron microscopy. Immunofluorescence staining was performed to detect the co-expression of endothelial markers, such as CD31, and fibroblast markers, such as fibroblast-specific protein 1 (FSP-1. The expression of FSP-1 was detected by real time-PCR and western blots. Endothelial-derived MSCs were grown in MSC medium for one week. The expression of the MSCs markers STRO-1, CD44, CD10 and the chondrocyte marker SOX9 was detected by immunofluorescence staining and western blots. Chondrocyte expression was detected by alcian blue staining. Calcium deposits were analyzed by alizarin red staining. Results The incubation of HAECs exposed to HG resulted in a fibroblast-like phenotype. Double staining of the HAECs indicated a co-localization of CD31 and FSP-1. The expression of FSP-1 was significantly increased in the HG group, and the cells undergoing EndMT also expressed STRO-1, CD44 and SOX9 compared with the controls (P  Conclusions Our

  1. High-Affinity Glucose Transport in Aspergillus nidulans Is Mediated by the Products of Two Related but Differentially Expressed Genes

    Science.gov (United States)

    Ventura, Luisa; González, Ramón; Ramón, Daniel; MacCabe, Andrew P.

    2014-01-01

    Independent systems of high and low affinity effect glucose uptake in the filamentous fungus Aspergillus nidulans. Low-affinity uptake is known to be mediated by the product of the mstE gene. In the current work two genes, mstA and mstC, have been identified that encode high-affinity glucose transporter proteins. These proteins' primary structures share over 90% similarity, indicating that the corresponding genes share a common origin. Whilst the function of the paralogous proteins is little changed, they differ notably in their patterns of expression. The mstC gene is expressed during the early phases of germination and is subject to CreA-mediated carbon catabolite repression whereas mstA is expressed as a culture tends toward carbon starvation. In addition, various pieces of genetic evidence strongly support allelism of mstC and the previously described locus sorA. Overall, our data define MstC/SorA as a high-affinity glucose transporter expressed in germinating conidia, and MstA as a high-affinity glucose transporter that operates in vegetative hyphae under conditions of carbon limitation. PMID:24751997

  2. FLIP switches Fas-mediated glucose signaling in human pancreatic β cells from apoptosis to cell replication

    Science.gov (United States)

    Maedler, Kathrin; Fontana, Adriano; Ris, Frédéric; Sergeev, Pavel; Toso, Christian; Oberholzer, José; Lehmann, Roger; Bachmann, Felix; Tasinato, Andrea; Spinas, Giatgen A.; Halban, Philippe A.; Donath, Marc Y.

    2002-01-01

    Type 2 diabetes mellitus results from an inadequate adaptation of the functional pancreatic β cell mass in the face of insulin resistance. Changes in the concentration of glucose play an essential role in the regulation of β cell turnover. In human islets, elevated glucose concentrations impair β cell proliferation and induce β cell apoptosis via up-regulation of the Fas receptor. Recently, it has been shown that the caspase-8 inhibitor FLIP may divert Fas-mediated death signals into those for cell proliferation in lymphatic cells. We observed expression of FLIP in human pancreatic β cells of nondiabetic individuals, which was decreased in tissue sections of type 2 diabetic patients. In vitro exposure of islets from nondiabetic organ donors to high glucose levels decreased FLIP expression and increased the percentage of apoptotic terminal deoxynucleotidyltransferase-mediated UTP end labeling (TUNEL)-positive β cells; FLIP was no longer detectable in such TUNEL-positive β cells. Up-regulation of FLIP, by incubation with transforming growth factor β or by transfection with an expression vector coding for FLIP, protected β cells from glucose-induced apoptosis, restored β cell proliferation, and improved β cell function. The beneficial effects of FLIP overexpression were blocked by an antagonistic anti-Fas antibody, indicating their dependence on Fas receptor activation. The present data provide evidence for expression of FLIP in the human β cell and suggest a novel approach to prevent and treat diabetes by switching Fas signaling from apoptosis to proliferation. PMID:12060768

  3. High-affinity glucose transport in Aspergillus nidulans is mediated by the products of two related but differentially expressed genes.

    Directory of Open Access Journals (Sweden)

    Josep V Forment

    Full Text Available Independent systems of high and low affinity effect glucose uptake in the filamentous fungus Aspergillus nidulans. Low-affinity uptake is known to be mediated by the product of the mstE gene. In the current work two genes, mstA and mstC, have been identified that encode high-affinity glucose transporter proteins. These proteins' primary structures share over 90% similarity, indicating that the corresponding genes share a common origin. Whilst the function of the paralogous proteins is little changed, they differ notably in their patterns of expression. The mstC gene is expressed during the early phases of germination and is subject to CreA-mediated carbon catabolite repression whereas mstA is expressed as a culture tends toward carbon starvation. In addition, various pieces of genetic evidence strongly support allelism of mstC and the previously described locus sorA. Overall, our data define MstC/SorA as a high-affinity glucose transporter expressed in germinating conidia, and MstA as a high-affinity glucose transporter that operates in vegetative hyphae under conditions of carbon limitation.

  4. A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability

    Directory of Open Access Journals (Sweden)

    Salvatore Fusco

    2016-02-01

    Full Text Available Adult neurogenesis plays increasingly recognized roles in brain homeostasis and repair and is profoundly affected by energy balance and nutrients. We found that the expression of Hes-1 (hairy and enhancer of split 1 is modulated in neural stem and progenitor cells (NSCs by extracellular glucose through the coordinated action of CREB (cyclic AMP responsive element binding protein and Sirt-1 (Sirtuin 1, two cellular nutrient sensors. Excess glucose reduced CREB-activated Hes-1 expression and results in impaired cell proliferation. CREB-deficient NSCs expanded poorly in vitro and did not respond to glucose availability. Elevated glucose also promoted Sirt-1-dependent repression of the Hes-1 promoter. Conversely, in low glucose, CREB replaced Sirt-1 on the chromatin associated with the Hes-1 promoter enhancing Hes-1 expression and cell proliferation. Thus, the glucose-regulated antagonism between CREB and Sirt-1 for Hes-1 transcription participates in the metabolic regulation of neurogenesis.

  5. Glucose-mediated control of ghrelin release from primary cultures of gastric mucosal cells

    OpenAIRE

    Sakata, Ichiro; Park, Won-Mee; Walker, Angela K.; Piper, Paul K.; Chuang, Jen-Chieh; Osborne-Lawrence, Sherri; Zigman, Jeffrey M.

    2012-01-01

    The peptide hormone ghrelin is released from a distinct group of gastrointestinal cells in response to caloric restriction, whereas its levels fall after eating. The mechanisms by which ghrelin secretion is regulated remain largely unknown. Here, we have used primary cultures of mouse gastric mucosal cells to investigate ghrelin secretion, with an emphasis on the role of glucose. Ghrelin secretion from these cells upon exposure to different d-glucose concentrations, the glucose antimetabolite...

  6. Deficiency of ACE2 in Bone-Marrow-Derived Cells Increases Expression of TNF-α in Adipose Stromal Cells and Augments Glucose Intolerance in Obese C57BL/6 Mice

    Directory of Open Access Journals (Sweden)

    Sean E. Thatcher

    2012-01-01

    Full Text Available Deficiency of ACE2 in macrophages has been suggested to promote the development of an inflammatory M1 macrophage phenotype. We evaluated effects of ACE2 deficiency in bone-marrow-derived stem cells on adipose inflammation and glucose tolerance in C57BL/6 mice fed a high fat (HF diet. ACE2 activity was increased in the stromal vascular fraction (SVF isolated from visceral, but not subcutaneous adipose tissue of HF-fed mice. Deficiency of ACE2 in bone marrow cells significantly increased mRNA abundance of F4/80 and TNF-α in the SVF isolated from visceral adipose tissue of HF-fed chimeric mice, supporting increased presence of inflammatory macrophages in adipose tissue. Moreover, deficiency of ACE2 in bone marrow cells modestly augmented glucose intolerance in HF-fed chimeric mice and increased blood levels of glycosylated hemoglobin. In summary, ACE2 deficiency in bone marrow cells promotes inflammation in adipose tissue and augments obesity-induced glucose intolerance.

  7. Correction of Diabetic Hyperglycemia and Amelioration of Metabolic Anomalies by Minicircle DNA Mediated Glucose-Dependent Hepatic Insulin Production.

    Directory of Open Access Journals (Sweden)

    Tausif Alam

    Full Text Available Type 1 diabetes mellitus (T1DM is caused by immune destruction of insulin-producing pancreatic β-cells. Commonly used insulin injection therapy does not provide a dynamic blood glucose control to prevent long-term systemic T1DM-associated damages. Donor shortage and the limited long-term success of islet transplants have stimulated the development of novel therapies for T1DM. Gene therapy-based glucose-regulated hepatic insulin production is a promising strategy to treat T1DM. We have developed gene constructs which cause glucose-concentration-dependent human insulin production in liver cells. A novel set of human insulin expression constructs containing a combination of elements to improve gene transcription, mRNA processing, and translation efficiency were generated as minicircle DNA preparations that lack bacterial and viral DNA. Hepatocytes transduced with the new constructs, ex vivo, produced large amounts of glucose-inducible human insulin. In vivo, insulin minicircle DNA (TA1m treated streptozotocin (STZ-diabetic rats demonstrated euglycemia when fasted or fed, ad libitum. Weight loss due to uncontrolled hyperglycemia was reversed in insulin gene treated diabetic rats to normal rate of weight gain, lasting ∼1 month. Intraperitoneal glucose tolerance test (IPGT demonstrated in vivo glucose-responsive changes in insulin levels to correct hyperglycemia within 45 minutes. A single TA1m treatment raised serum albumin levels in diabetic rats to normal and significantly reduced hypertriglyceridemia and hypercholesterolemia. Elevated serum levels of aspartate transaminase, alanine aminotransferase, and alkaline phosphatase were restored to normal or greatly reduced in treated rats, indicating normalization of liver function. Non-viral insulin minicircle DNA-based TA1m mediated glucose-dependent insulin production in liver may represent a safe and promising approach to treat T1DM.

  8. Involvement of functional groups on the surface of carboxyl group-terminated polyamidoamine dendrimers bearing arbutin in inhibition of Na⁺/glucose cotransporter 1 (SGLT1)-mediated D-glucose uptake.

    Science.gov (United States)

    Sakuma, Shinji; Kanamitsu, Shun; Teraoka, Yumi; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Shirasaka, Yoshiyuki; Tamai, Ikumi; Muraoka, Masahiro; Nakatsuji, Yohji; Kida, Toshiyuki; Akashi, Mitsuru

    2012-04-01

    A carboxyl group-terminated polyamidoamine dendrimer (generation: 3.0) bearing arbutin, which is a substrate of Na⁺/glucose cotransporter 1 (SGLT1), via a nonbiodegradable ω-amino triethylene glycol linker (PAMAM-ARB), inhibits SGLT1-mediated D-glucose uptake, as does phloridzin, which is a typical SGLT1 inhibitor. Here, since our previous research revealed that the activity of arbutin was dramatically improved through conjugation with the dendrimer, we examined the involvement of functional groups on the dendrimer surface in inhibition of SGLT1-mediated D-glucose uptake. PAMAM-ARB, with a 6.25% arbutin content, inhibited in vitro D-glucose uptake most strongly; the inhibitory effect decreased as the arbutin content increased. In vitro experiments using arbutin-free original dendrimers indicated that dendrimer-derived carboxyl groups actively participated in SGLT1 inhibition. However, the inhibitory effect was much less than that of PAMAM-ARB and was equal to that of glucose moiety-free PAMAM-ARB. Data supported that the glucose moiety of arbutin was essential for the high activity of PAMAM-ARB in SGLT1 inhibition. Analysis of the balance of each domain further suggested that carboxyl groups anchored PAMAM-ARB to SGLT1, and the subsequent binding of arbutin-derived glucose moieties to the target sites on SGLT1 resulted in strong inhibition of SGLT1-mediated D-glucose uptake.

  9. BH3-only protein Bim is upregulated and mediates the apoptosis of cardiomyocytes under glucose and oxygen-deprivation conditions.

    Science.gov (United States)

    Huang, Chahua; Li, Juxiang; Hong, Kui; Xia, Zhen; Xu, Yan; Cheng, Xiaoshu

    2015-03-01

    Bim is a potent pro-apoptotic BH3-only Bcl-2 member. However, the expression of Bim and its role in cardiac injury induced by ischemia remain unclear. H9c2 cells were subjected to a glucose and oxygen-deprived (GOD) condition in vitro, mimicking ischemia environment in vivo. GOD treatment augmented the expression of Bim and induced the apoptosis of H9c2 cells. Silencing of Bim by RNAi significantly attenuated GOD-induced cytotoxicity, suppressed mitochondrial membrane potential △Ψm loss, inhibited caspase 3 activation and reduced apoptosis. The data demonstrate that Bim is upregulated by GOD in a time-dependent manner in H9c2 cells, and enhances mitochondrial apoptosis dependent on the activation of caspase 3. Silencing of Bim may be a promising therapeutic strategy in ischemia related heart diseases.

  10. Glucose is a key driver for GLUT1-mediated nanoparticles internalization in breast cancer cells

    Science.gov (United States)

    Venturelli, Leonardo; Nappini, Silvia; Bulfoni, Michela; Gianfranceschi, Giuseppe; Dal Zilio, Simone; Coceano, Giovanna; Del Ben, Fabio; Turetta, Matteo; Scoles, Giacinto; Vaccari, Lisa; Cesselli, Daniela; Cojoc, Dan

    2016-02-01

    The mesenchymal state in cancer is usually associated with poor prognosis due to the metastatic predisposition and the hyper-activated metabolism. Exploiting cell glucose metabolism we propose a new method to detect mesenchymal-like cancer cells. We demonstrate that the uptake of glucose-coated magnetic nanoparticles (MNPs) by mesenchymal-like cells remains constant when the glucose in the medium is increased from low (5.5 mM) to high (25 mM) concentration, while the MNPs uptake by epithelial-like cells is significantly reduced. These findings reveal that the glucose-shell of MNPs plays a major role in recognition of cells with high-metabolic activity. By selectively blocking the glucose transporter 1 channels we showed its involvement in the internalization process of glucose-coated MNPs. Our results suggest that glucose-coated MNPs can be used for metabolic-based assays aimed at detecting cancer cells and that can be used to selectively target cancer cells taking advantage, for instance, of the magnetic-thermotherapy.

  11. Augmented Reality for Augmented Reality

    OpenAIRE

    Pankratz, Frieder

    2016-01-01

    A recurring challenge when setting up any augmented reality system is the correct calibration and registration of the involved devices. Augmented Reality for Augmented Reality (AR4AR) generates augmented reality guides by using the already existing knowledge about the AR system which stems from the setup of the AR system itself. As these guides involve plenty of 3D information, it is again best presented through means of Augmented Reality, thus the name AR4AR. Eine wiederkehrende Herausfor...

  12. Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet-Induced Insulin Resistance.

    Science.gov (United States)

    Zhang, Wei; Wu, Mengrui; Kim, Teayoun; Jariwala, Ravi H; Garvey, W John; Luo, Nanlan; Kang, Minsung; Ma, Elizabeth; Tian, Ling; Steverson, Dennis; Yang, Qinglin; Fu, Yuchang; Garvey, W Timothy

    2016-08-01

    In the current study, we used muscle-specific TRIB3 overexpressing (MOE) and knockout (MKO) mice to determine whether TRIB3 mediates glucose-induced insulin resistance in diabetes and whether alterations in TRIB3 expression as a function of nutrient availability have a regulatory role in metabolism. In streptozotocin diabetic mice, TRIB3 MOE exacerbated, whereas MKO prevented, glucose-induced insulin resistance and impaired glucose oxidation and defects in insulin signal transduction compared with wild-type (WT) mice, indicating that glucose-induced insulin resistance was dependent on TRIB3. In response to a high-fat diet, TRIB3 MOE mice exhibited greater weight gain and worse insulin resistance in vivo compared with WT mice, coupled with decreased AKT phosphorylation, increased inflammation and oxidative stress, and upregulation of lipid metabolic genes coupled with downregulation of glucose metabolic genes in skeletal muscle. These effects were prevented in the TRIB3 MKO mice relative to WT mice. In conclusion, TRIB3 has a pathophysiological role in diabetes and a physiological role in metabolism. Glucose-induced insulin resistance and insulin resistance due to diet-induced obesity both depend on muscle TRIB3. Under physiological conditions, muscle TRIB3 also influences energy expenditure and substrate metabolism, indicating that the decrease and increase in muscle TRIB3 under fasting and nutrient excess, respectively, are critical for metabolic homeostasis. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. The reduced insulin-mediated glucose oxidation in skeletal muscle from type 2 diabetic subjects may be of genetic origin--evidence from cultured myotubes.

    Science.gov (United States)

    Gaster, Michael; Beck-Nielsen, Henning

    2004-09-06

    Several defects in response to insulin have been described in vivo and in vitro in type 2 diabetes: a decreased glucose transport, defective glucose oxidation and altered glycogen synthesis. At present, it is unknown whether glucose oxidation is primarily affected or secondarily affected by, e.g. increased free fatty acids (FFA). The aim of this study was to evaluate whether myotubes established from type 2 diabetic subjects express a primarily or a FFA-induced reduced insulin-mediated glucose oxidation. We have therefore investigated glucose oxidation under basal, physiological conditions and during acute insulin stimulation with/without FFA. We found that myotubes established from type 2 diabetic subjects express a reduced insulin-stimulated increase in glucose oxidation. Moreover, an acute exposure to FFA reduces insulin-mediated glucose oxidation without alterations in glucose uptake and glycogen synthesis. Thus, we conclude that the diminished increase in insulin-stimulated glucose oxidation seen in type 2 diabetic subjects in vivo may be of genetic origin. Moreover, the glucose-fatty acid cycle seems not to be crucial for the pathophysiology of insulin resistance.

  14. Hyperactivation of 4E-binding protein 1 as a mediator of biguanide-induced cytotoxicity during glucose deprivation.

    Science.gov (United States)

    Matsuo, Junichi; Tsukumo, Yoshinori; Saito, Sakae; Tsukahara, Satomi; Sakurai, Junko; Sato, Shigeo; Kondo, Hiromichi; Ushijima, Masaru; Matsuura, Masaaki; Watanabe, Toshiki; Tomida, Akihiro

    2012-05-01

    Biguanides, including metformin, buformin, and phenformin, are potential antitumorigenic agents and induce cell death during glucose deprivation, a cell condition that occurs in the tumor microenvironment. Here, we show that this selective killing of glucose-deprived cells is coupled with hyperactivation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), a negative regulator of translation initiation. We found, in fact, that the 4E-BP1 hyperactivation led to failure of the unfolded protein response (UPR), an endoplasmic reticulum-originated stress signaling pathway for cell survival. We also found that the 4E-BP1-mediated UPR inhibition occurred through a strong inhibition of the mTOR signaling pathway, a proven antitumor target. Importantly, the 4E-BP1 hyperactivation can be also seen in xenografted cancer cells through an in vivo biguanide treatment. Our findings indicate that antitumor action of biguanides can be mediated by 4E-BP1 hyperactivation, which results in UPR inhibition and selective cell killing when glucose is withdrawn.

  15. A new amperometric glucose biosensor based on screen printed carbon electrodes with rhenium(IV - oxide as a mediator

    Directory of Open Access Journals (Sweden)

    ALBANA VESELI

    2012-11-01

    Full Text Available Rhenium(IV-oxide, ReO2, was used as a mediator for carbon paste (CPE and screen printed carbon (SPCE electrodes for the catalytic amperometric determination of hydro-gen peroxide, whose overpotential for the reduction could be lowered to -0.1 V vs. Ag/AgCl in flow injection analysis (FIA using phosphate buffer (0.1 M, pH=7.5 as a carrier. For hydrogen peroxide a detection limit (3σ of 0.8 mg L-1 could be obtained.ReO2-modified SPCEs were used to design biosensors with a template enzyme, i.e. glucose oxidase, entrapped in a Nafion membrane. The resulting glucose sensor showed a linear dynamic range up to 200 mg L-1 glucose with a detection limit (3σ of 0.6 mg L-1. The repeatability was 2.1 % RSD (n = 5 measurements, the reproducibility 5.4 % (n = 5 sensors. The sensor could be applied for the determination of glucose in blood serum in good agreement with a reference method.

  16. Glucose Signaling-Mediated Coordination of Cell Growth and Cell Cycle in Saccharomyces Cerevisiae

    Directory of Open Access Journals (Sweden)

    Stefano Busti

    2010-06-01

    Full Text Available Besides being the favorite carbon and energy source for the budding yeast Sacchromyces cerevisiae, glucose can act as a signaling molecule to regulate multiple aspects of yeast physiology. Yeast cells have evolved several mechanisms for monitoring the level of glucose in their habitat and respond quickly to frequent changes in the sugar availability in the environment: the cAMP/PKA pathways (with its two branches comprising Ras and the Gpr1/Gpa2 module, the Rgt2/Snf3-Rgt1 pathway and the main repression pathway involving the kinase Snf1. The cAMP/PKA pathway plays the prominent role in responding to changes in glucose availability and initiating the signaling processes that promote cell growth and division. Snf1 (the yeast homologous to mammalian AMP-activated protein kinase is primarily required for the adaptation of yeast cell to glucose limitation and for growth on alternative carbon source, but it is also involved in the cellular response to various environmental stresses. The Rgt2/Snf3-Rgt1 pathway regulates the expression of genes required for glucose uptake. Many interconnections exist between the diverse glucose sensing systems, which enables yeast cells to fine tune cell growth, cell cycle and their coordination in response to nutritional changes.

  17. Calpain activation induced by glucose deprivation is mediated by oxidative stress and contributes to neuronal damage.

    Science.gov (United States)

    Páramo, Blanca; Montiel, Teresa; Hernández-Espinosa, Diego R; Rivera-Martínez, Marlene; Morán, Julio; Massieu, Lourdes

    2013-11-01

    The mechanisms leading to neuronal death during glucose deprivation have not been fully elucidated, but a role of oxidative stress has been suggested. In the present study we have investigated whether the production of reactive oxygen species during glucose deprivation, contributes to the activation of calpain, a calcium-dependent protease involved in neuronal injury associated with brain ischemia and cerebral trauma. We have observed a rapid activation of calpain, as monitored by the cleavage of the cytoskeletal protein α-spectrin, after glucose withdrawal, which is reduced by inhibitors of xanthine oxidase, phospholipase A2 and NADPH oxidase. Results suggest that phospholipase A2 and NADPH oxidase contribute to the early activation of calpain after glucose deprivation. In particular NOX2, a member of the NADPH oxidase family is involved, since reduced stimulation of calpain activity is observed after glucose deprivation in hippocampal slices from transgenic mice lacking a functional NOX2. We observed an additive effect of the inhibitors of xanthine oxidase and phospholipase A2 on both ROS production and calpain activity, suggesting a synergistic action of these two enzymes. The present results provide new evidence showing that reactive oxygen species stimulate calpain activation during glucose deprivation and that this mechanism is involved in neuronal death.

  18. Inhibition of glucose- and fructose-mediated protein glycation by infusions and ethanolic extracts of ten culinary herbs and spices

    Institute of Scientific and Technical Information of China (English)

    Jugjeet Singh Ramkissoon; Mohamad Fawzi Mahomoodally; Anwar Hussein Subratty; Nessar Ahmed

    2016-01-01

    Objective: To investigate the inhibitory activity of ten culinary herbs and spices namely on glucose-mediated glycation (GMG) and fructose-mediated glycation (FMG) of bovine serum albumin. Methods: Fluorescence was used as an index of albumin glycation using glucose and fructose as substrates in the presence of infusions and ethanolic extracts of ten culinary herbs and spices. Antioxidant activity of the extracts was evaluated using reducing power, metal ion chelating and superoxide radical scavenging assays. Phytochemicals profile was analysed using 13 standard methods. Results: FMG was found to be significantly higher than GMG (95 and 84 AU, respectively; P 0.05) was found in the percentage glycation inhibitory activity of infusions compared to ethanolic extracts. The mean percentage inhibitory activity of the extracts for GMG (45.9%) and for FMG (45.1%) was not significantly different (P > 0.05). Qualitative phytochemical analysis showed the presence of alkaloids, fla-vonoids, tannins, terpenoids, anthraquinones, steroids, reducing sugars, proteins, phenols, saponins, phlobatannins, and cardiac glycosides. Conclusions: The higher rate of fluorescence generation by fructation suggests that glycation by fructose deserves much attention as a glycating agent. Data herein showed that the extracts inhibited GMG and FMG. Thus, these edible plants could be a natural source of antioxidants and anti-glycation agent for preventing advanced glycation end-products-mediated complications.

  19. Rapid insulin-mediated increase in microvascular glycocalyx accessibility in skeletal muscle may contribute to insulin-mediated glucose disposal in rats.

    Directory of Open Access Journals (Sweden)

    Bart J M Eskens

    Full Text Available It has been demonstrated that insulin-mediated recruitment of microvascular blood volume is associated with insulin sensitivity. We hypothesize that insulin rapidly stimulates penetration of red blood cells (RBC and plasma into the glycocalyx and thereby promotes insulin-mediated glucose uptake by increasing intracapillary blood volume. Experiments were performed in rats; the role of the glycocalyx was assessed by enzymatic degradation using a bolus of hyaluronidase. First, the effect of insulin on glycocalyx accessibility was assessed by measuring the depth of penetration of RBCs into the glycocalyx in microvessels of the gastrocnemius muscle with Sidestream Dark-field imaging. Secondly, peripheral insulin sensitivity was determined using intravenous insulin tolerance tests (IVITT. In addition, in a smaller set of experiments, intravital microscopy of capillary hemodynamics in cremaster muscle and histological analysis of the distribution of fluorescently labeled 40 kDa dextrans (D40 in hindlimb muscle was used to evaluate insulin-mediated increases in capillary blood volume. Insulin increased glycocalyx penetration of RBCs by 0.34±0.44 µm (P<0.05 within 10 minutes, and this effect of insulin was greatly impaired in hyaluronidase treated rats. Further, hyaluronidase treated rats showed a 35±25% reduction in whole-body insulin-mediated glucose disposal compared to control rats. Insulin-mediated increases in capillary blood volume were reflected by a rapid increase in capillary tube hematocrit from 21.1±10.1% to 29.0±9.8% (P<0.05, and an increase in D40 intensity in individual capillaries of 134±138% compared to baseline at the end of the IVITT. These effects of insulin were virtually abolished in hyaluronidase treated animals. In conclusion, insulin rapidly increases glycocalyx accessibility for circulating blood in muscle, and this is associated with an increased blood volume in individual capillaries. Hyaluronidase treatment of the

  20. HIF-1 and c-Src mediate increased glucose uptake induced by endothelin-1 and connexin43 in astrocytes.

    Directory of Open Access Journals (Sweden)

    José Carlos Valle-Casuso

    Full Text Available In previous work we showed that endothelin-1 (ET-1 increases the rate of glucose uptake in astrocytes, an important aspect of brain function since glucose taken up by astrocytes is used to supply the neurons with metabolic substrates. In the present work we sought to identify the signalling pathway responsible for this process in primary culture of rat astrocytes. Our results show that ET-1 promoted an increase in the transcription factor hypoxia-inducible factor-1α (HIF-1α in astrocytes, as shown in other cell types. Furthermore, HIF-1α-siRNA experiments revealed that HIF-1α participates in the effects of ET-1 on glucose uptake and on the expression of GLUT-1, GLUT-3, type I and type II hexokinase. We previously reported that these effects of ET-1 are mediated by connexin43 (Cx43, the major gap junction protein in astrocytes. Indeed, our results show that silencing Cx43 increased HIF-1α and reduced the effect of ET-1 on HIF-1α, indicating that the effect of ET-1 on HIF-1α is mediated by Cx43. The activity of oncogenes such as c-Src can up-regulate HIF-1α. Since Cx43 interacts with c-Src, we investigated the participation of c-Src in this pathway. Interestingly, both the treatment with ET-1 and with Cx43-siRNA increased c-Src activity. In addition, when c-Src activity was inhibited neither ET-1 nor silencing Cx43 were able to up-regulate HIF-1α. In conclusion, our results suggest that ET-1 by down-regulating Cx43 activates c-Src, which in turn increases HIF-1α leading to the up-regulation of the machinery required to take up glucose in astrocytes. Cx43 expression can be reduced in response not only to ET-1 but also to various physiological and pathological stimuli. This study contributes to the identification of the signalling pathway evoked after Cx43 down-regulation that results in increased glucose uptake in astrocytes. Interestingly, this is the first evidence linking Cx43 to HIF-1, which is a master regulator of glucose metabolism.

  1. Activatory and inhibitory Fcγ receptors augment rituximab-mediated internalization of CD20 independent of signaling via the cytoplasmic domain.

    Science.gov (United States)

    Vaughan, Andrew T; Chan, Claude H T; Klein, Christian; Glennie, Martin J; Beers, Stephen A; Cragg, Mark S

    2015-02-27

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes.

  2. Kinetics of interfacial radical polymerization initiated by a glucose-oxidase mediated redox system.

    Science.gov (United States)

    Shenoy, Raveesh; Bowman, Christopher N

    2012-10-01

    The reaction and coating kinetics for the glucose oxidase initiated interfacial polymerization are elaborated. The interfacial film grows rapidly and linearly with time, producing time-dependent controllable conformal coating thicknesses of up to a millimeter in less than 4 min. Bulk polymerization was only observed when the immersing media was stirred to induce higher mass transport rates. The dramatically different film thicknesses observed between different concentrations of glucose in the hydrogel and iron in the bulk media are demonstrated to be a result of an initial rapid growth phase following which the film grows at the same rate nearly independent of either the glucose or iron concentration. The polymerization rate and hence the thickness growth rate in this initial phase saturate at glucose and iron concentrations above 0.8 M and 0.63 mM, respectively. At iron concentrations above 0.05 mM, the film thickness at the end of 3 h of reaction monotonically decreased with increasing iron concentration from 5.7 mm to 4.2 mm. The glucose oxidase is trapped by the growing polymerization front and can be used as the sole enzymatic precursor to coat a second polymeric layer. However, the rate of film growth of the second layer is 14-fold lower than the rate of film growth when bulk enzyme is present during the second stage coating process.

  3. The PPAR α / γ Agonist, Tesaglitazar, Improves Insulin Mediated Switching of Tissue Glucose and Free Fatty Acid Utilization In Vivo in the Obese Zucker Rat.

    Science.gov (United States)

    Wallenius, Kristina; Kjellstedt, Ann; Thalén, Pia; Löfgren, Lars; Oakes, Nicholas D

    2013-01-01

    lean controls, obese controls, and obese rats treated with the dual peroxisome proliferator activated receptor (PPAR) α/γ agonist, tesaglitazar, 3  μ mol/kg/day for 3 weeks. Whole body glucose disposal rate (R d ) and hepatic glucose output (HGO) were assessed under basal fasting and hyperinsulinemic isoglycemic clamp conditions using [3,(3)H]glucose. Indices of tissue specific glucose utilization (R g ') were measured at basal, physiological, and supraphysiological levels of insulinemia using 2-deoxy-D-[2,6-(3)H]glucose. Finally, whole body and tissue specific FFA and glucose utilization and metabolic fate were evaluated under basal and hyperinsulinemic conditions using a combination of [U-(13)C]glucose, 2-deoxy-D-[U-(14)C]glucose, [U-(14)C]palmitate, and [9,10-(3)H]-(R)-bromopalmitate. Tesaglitazar improved whole body insulin action by greater suppression of HGO and stimulation of R d compared to obese controls. This involved increased insulin stimulation of R g ' in fat and skeletal muscle as well as increased glycogen synthesis. Tesaglitazar dramatically improved insulin mediated suppression of plasma FFA level, whole body turnover (R fa ), and muscle, liver, and fat utilization. At basal insulin levels, tesaglitazar failed to lower HGO or R fa compared to obese controls. In conclusion, the results demonstrate that tesaglitazar has a remarkable ability to improve insulin mediated control of glucose and FFA fluxes in obese Zucker rats.

  4. GLUT1-mediated glucose uptake plays a crucial role during Plasmodium hepatic infection.

    Science.gov (United States)

    Meireles, Patrícia; Sales-Dias, Joana; Andrade, Carolina M; Mello-Vieira, João; Mancio-Silva, Liliana; Simas, J Pedro; Staines, Henry M; Prudêncio, Miguel

    2017-02-01

    Intracellular pathogens have evolved mechanisms to ensure their survival and development inside their host cells. Here, we show that glucose is a pivotal modulator of hepatic infection by the rodent malaria parasite Plasmodium berghei and that glucose uptake via the GLUT1 transporter is specifically enhanced in P. berghei-infected cells. We further show that ATP levels of cells containing developing parasites are decreased, which is known to enhance membrane GLUT1 activity. In addition, GLUT1 molecules are translocated to the membrane of the hepatic cell, increasing glucose uptake at later stages of infection. Chemical inhibition of GLUT1 activity leads to a decrease in glucose uptake and the consequent impairment of hepatic infection, both in vitro and in vivo. Our results reveal that changes in GLUT1 conformation and cellular localization seem to be part of an adaptive host response to maintain adequate cellular nutrition and energy levels, ensuring host cell survival and supporting P. berghei hepatic development. © 2016 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.

  5. Central insulin and leptin-mediated autonomic control of glucose homeostasis

    Science.gov (United States)

    Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucos...

  6. IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival.

    Science.gov (United States)

    Wofford, Jessica A; Wieman, Heather L; Jacobs, Sarah R; Zhao, Yuxing; Rathmell, Jeffrey C

    2008-02-15

    Lymphocyte homeostasis requires coordination of metabolic processes with cellular energetic and biosynthetic demands but mechanisms that regulate T-cell metabolism are uncertain. We show that interleukin-7 (IL-7) is a key regulator of glucose uptake in T lymphocytes. To determine how IL-7 affects glucose uptake, we analyzed IL-7 signaling mechanisms and regulation of the glucose transporter, Glut1. The IL-7 receptor (IL-7R) stimulated glucose uptake and cell-surface localization of Glut1 in a manner that required IL-7R Y449, which promoted rapid signal transducer and activator of transcription 5 (STAT5) activation and a delayed yet sustained activation of Akt. Each pathway was necessary for IL-7 to promote glucose uptake, as Akt1(-/-) T cells or PI3-kinase inhibition and RNAi of STAT5 led to defective glucose uptake in response to IL-7. STAT5 and Akt acted in a linear pathway, with STAT5-mediated transcription leading to Akt activation, which was necessary for STAT5 and IL-7 to promote glucose uptake and prevent cell death. Importantly, IL-7 required glucose uptake to promote cell survival. These data demonstrate that IL-7 promotes glucose uptake via a novel signaling mechanism in which STAT5 transcriptional activity promotes Akt activation to regulate Glut1 trafficking and glucose uptake that is critical for IL-7 to prevent T-cell death and maintain homeostasis.

  7. Detoxification of tabun at physiological pH mediated by substituted β-cyclodextrin and glucose derivatives containing oxime groups.

    Science.gov (United States)

    Brandhuber, Florian; Zengerle, Michael; Porwol, Luzian; Tenberken, Oliver; Thiermann, Horst; Worek, Franz; Kubik, Stefan; Reiter, Georg

    2012-12-16

    The ability of 13 β-cyclodextrin and 2 glucose derivatives containing substituents with oxime groups as nucleophilic components to accelerate the degradation of tabun at physiological pH has been evaluated. To this end, a qualitative and a quantitative enzymatic assay as well as a highly sensitive enantioselective GC-MS assay were used. In addition, an assay was developed that provided information about the mode of action of the investigated compounds. The results show that attachment of pyridinium-derived substituents with an aldoxime group in 3- or 4-position to a β-cyclodextrin ring affords active compounds mediating tabun degradation. Activities differ depending on the structure, the number, and the position of the substituent on the ring. Highest activity was observed for a β-cyclodextrin containing a 4-formylpyridinium oxime residue in 6-position of one glucose subunit, which detoxifies tabun with a half-time of 10.2 min. Comparison of the activity of this compound with that of an analog in which the cyclodextrin ring was replaced by a glucose residue demonstrated that the cyclodextrin is not necessary for activity but certainly beneficial. Finally, the results provide evidence that the mode of action of the cyclodextrin involves covalent modification of its oxime group rendering the scavenger inactive after reaction with the first tabun molecule.

  8. Seed-mediated synthesis of copper nanoparticles on carbon nanotubes and their application in nonenzymatic glucose biosensors.

    Science.gov (United States)

    Lu, Li-Min; Zhang, Xiao-Bing; Shen, Guo-Li; Yu, Ru-Qin

    2012-02-17

    In this paper, for the first time, Cu nanoparticles (CuNPs) were prepared by seed-mediated growth method with Au nanoparticles (AuNPs) playing the role of seeds. Carbon nanotubes (CNTs) and AuNPs were first dropped on the surface of glassy carbon (GC) electrode, and then the electrode was immersed into growth solution that contained CuSO(4) and hydrazine. CuNPs were successfully grown on the surface of the CNTs. The modified electrode showed a very high electrochemical activity for electrocatalytic oxidation of glucose in alkaline medium, which was utilized as the basis of the fabrication of a nonenzymatic biosensor for electrochemical detection of glucose. The biosensor can be applied to the quantification of glucose with a linear range covering from 1.0×10(-7) to 5×10(-3)M and a low detection limit of 3×10(-8)M. Furthermore, the experiment results also showed that the biosensor exhibited good reproducibility and long-term stability, as well as high selectivity with no interference from other oxidable species. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Potentiation of Insulin-Mediated Glucose Lowering without Elevated Hypoglycemia Risk by a Small Molecule Insulin Receptor Modulator

    Science.gov (United States)

    Wu, Margaret; Dai, Ge; Yao, Jun; Hoyt, Scott; Wang, Liangsu; Mu, James

    2015-01-01

    Insulin resistance is the key feature of type 2 diabetes and is manifested as attenuated insulin receptor (IR) signaling in response to same levels of insulin binding. Several small molecule IR activators have been identified and reported to exhibit insulin sensitization properties. One of these molecules, TLK19781 (Cmpd1), was investigated to examine its IR sensitizing action in vivo. Our data demonstrate that Cmpd1, at doses that produced minimal efficacy in the absence of insulin, potentiated insulin action during an OGTT in non-diabetic mice and enhanced insulin-mediated glucose lowering in diabetic mice. Interestingly, different from insulin alone, Cmpd1 combined with insulin showed enhanced efficacy and duration of action without increased hypoglycemia. To explore the mechanism underlying the apparent glucose dependent efficacy, tissue insulin signaling was compared in healthy and diabetic mice. Cmpd1 enhanced insulin’s effects on IR phosphorylation in both healthy and diabetic mice. In contrast, the compound potentiated insulin’s effects on Akt phosphorylation in diabetic but not in non-diabetic mice. These differential effects on signaling corresponding to glucose levels could be part of the mechanism for reduced hypoglycemia risk. The in vivo efficacy of Cmpd1 is specific and dependent on IR expression. Results from these studies support the idea of targeting IR for insulin sensitization, which carries low hypoglycemia risk by standalone treatment and could improve the effectiveness of insulin therapies. PMID:25799496

  10. Biosensor Based on TTF@SiO2 Nanoparticles as Electron Transfer Mediator for the Determination of Glucose

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Tetrathiafulvalene(TTF) was doped in an SiO2 network and the resulting nanocomposite was used as a mediator for the selective detection of glucose. The uniform TTF-doped silica(TTF@SiO2) nanoparticles were prepared by the water-in-oil(W/O) microemulsion method, and were characterized by transmission electron microscopy(TEM). The core-shell structure TTF@SiO2 could prevent TTF from leaching out into an aqueous solution. Combined with chitosan(CHIT), which serves as a scaffold for glucose oxidase and nanocomposite immobilization, the GCE/TTF@SiO2-CHIT-GOx biosensor was developed. Under optimal conditions, the biosensors exhibit a linear range of 1.0×10-5-5×10-3 mol/L with a detection limit down to 5.0 μmol/L(S/N=3). The excellent selectivity, sensitivity, and stability of the glucose biosensor show its potential for practical applications.

  11. Fyn Mediates High Glucose-Induced Actin Cytoskeleton Reorganization of Podocytes via Promoting ROCK Activation In Vitro

    Directory of Open Access Journals (Sweden)

    Zhimei Lv

    2016-01-01

    Full Text Available Fyn, a member of the Src family of tyrosine kinases, is a key regulator in cytoskeletal remodeling in a variety of cell types. Recent studies have demonstrated that Fyn is responsible for nephrin tyrosine phosphorylation, which will result in polymerization of actin filaments and podocyte damage. Thus detailed involvement of Fyn in podocytes is to be elucidated. In this study, we investigated the potential role of Fyn/ROCK signaling and its interactions with paxillin. Our results presented that high glucose led to filamentous actin (F-actin rearrangement in podocytes, accompanied by paxillin phosphorylation and increased cell motility, during which Fyn and ROCK were markedly activated. Gene knockdown of Fyn by siRNA showed a reversal effect on high glucose-induced podocyte damage and ROCK activation; however, inhibition of ROCK had no significant effects on Fyn phosphorylation. These observations demonstrate that in vitro Fyn mediates high glucose-induced actin cytoskeleton remodeling of podocytes via promoting ROCK activation and paxillin phosphorylation.

  12. ARAP2 promotes GLUT1-mediated basal glucose uptake through regulation of sphingolipid metabolism.

    Science.gov (United States)

    Chaudhari, Aditi; Håversen, Liliana; Mobini, Reza; Andersson, Linda; Ståhlman, Marcus; Lu, Emma; Rutberg, Mikael; Fogelstrand, Per; Ekroos, Kim; Mardinoglu, Adil; Levin, Malin; Perkins, Rosie; Borén, Jan

    2016-11-01

    Lipid droplet formation, which is driven by triglyceride synthesis, requires several droplet-associated proteins. We identified ARAP2 (an ADP-ribosylation factor 6 GTPase-activating protein) in the lipid droplet proteome of NIH-3T3 cells and showed that knockdown of ARAP2 resulted in decreased lipid droplet formation and triglyceride synthesis. We also showed that ARAP2 knockdown did not affect fatty acid uptake but reduced basal glucose uptake, total levels of the glucose transporter GLUT1, and GLUT1 levels in the plasma membrane and the lipid micro-domain fraction (a specialized plasma membrane domain enriched in sphingolipids). Microarray analysis showed that ARAP2 knockdown altered expression of genes involved in sphingolipid metabolism. Because sphingolipids are known to play a key role in cell signaling, we performed lipidomics to further investigate the relationship between ARAP2 and sphingolipids and potentially identify a link with glucose uptake. We found that ARAP2 knockdown increased glucosylceramide and lactosylceramide levels without affecting ceramide levels, and thus speculated that the rate-limiting enzyme in glycosphingolipid synthesis, namely glucosylceramide synthase (GCS), could be modified by ARAP2. In agreement with our hypothesis, we showed that the activity of GCS was increased by ARAP2 knockdown and reduced by ARAP2 overexpression. Furthermore, pharmacological inhibition of GCS resulted in increases in basal glucose uptake, total GLUT1 levels, triglyceride biosynthesis from glucose, and lipid droplet formation, indicating that the effects of GCS inhibition are the opposite to those resulting from ARAP2 knockdown. Taken together, our data suggest that ARAP2 promotes lipid droplet formation by modifying sphingolipid metabolism through GCS. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Cytosolic Pellino-1-Mediated K63-Linked Ubiquitination of IRF5 in M1 Macrophages Regulates Glucose Intolerance in Obesity

    Directory of Open Access Journals (Sweden)

    Donghyun Kim

    2017-07-01

    Full Text Available IRF5 is a signature transcription factor that induces M1 macrophage polarization. However, little is known regarding cytosolic proteins that induce IRF5 activation for M1 polarization. Here, we report the interaction between ubiquitin E3 ligase Pellino-1 and IRF5 in the cytoplasm, which increased nuclear translocation of IRF5 by K63-linked ubiquitination in human and mouse M1 macrophages. LPS and/or IFN-γ increased Pellino-1 expression, and M1 polarization was attenuated in Pellino-1-deficient macrophages in vitro and in vivo. Defective M1 polarization in Pellino-1-deficient macrophages improved glucose intolerance in mice fed a high-fat diet. Furthermore, macrophages in adipose tissues from obese humans exhibited increased Pellino-1 expression and IRF5 nuclear translocation compared with nonobese subjects, and these changes are associated with insulin resistance index. This study demonstrates that cytosolic Pellino-1-mediated K63-linked ubiquitination of IRF5 in M1 macrophages regulates glucose intolerance in obesity, suggesting a cytosolic mediator function of Pellino-1 in TLR4/IFN-γ receptor-IRF5 axis during M1 polarization.

  14. Role of Quinones in Electron Transfer of PQQ–Glucose Dehydrogenase Anodes—Mediation or Orientation Effect

    Energy Technology Data Exchange (ETDEWEB)

    Babanova, Sofia; Matanovic, Ivana; Chavez, Madelaine Seow; Atanassov, Plamen

    2015-06-24

    In this study, the influence of two quinones (1,2- and 1,4-benzoquinone) on the operation and mechanism of electron transfer in PQQ-dependent glucose dehydrogenase (PQQ–sGDH) anodes has been determined. Benzoquinones were experimentally explored as mediators present in the electrolyte. The electrochemical performance of the PQQ–sGDH anodes with and without the mediators was examined and for the first time molecular docking simulations were used to gain a fundamental understanding to explain the role of the mediator molecules in the design and operation of the enzymatic electrodes. It was proposed that the higher performance of the PQQ–sGDH anodes in the presence of 1,2- and 1,4-benzoquinones introduced in the solution is due to the shorter distance between these molecules and PQQ in the enzymatic molecule. It was also hypothesized that when 1,4-benzoquinone is adsorbed on a carbon support, it would play the dual role of a mediator and an orienting agent. At the same time, when 1,2-benzoquinone and ubiquinone are adsorbed on the electrode surface, the enzyme would transfer the electrons directly to the support, and these molecules would primarily play the role of an orienting agent.

  15. Expression of the human isoform of glutamate dehydrogenase, hGDH2, augments TCA cycle capacity and oxidative metabolism of glutamate during glucose deprivation in astrocytes

    DEFF Research Database (Denmark)

    Nissen, Jakob D; Lykke, Kasper; Bryk, Jaroslaw

    2016-01-01

    including CO2 , respectively. We conclude that hGDH2 expression increases capacity for uptake and oxidative metabolism of glutamate, particularly during increased workload and aglycemia. Additionally, hGDH2 expression increased utilization of branched-chain amino acids (BCAA) during aglycemia and caused...... a general decrease in oxidative glucose metabolism. We speculate, that expression of hGDH2 allows astrocytes to spare glucose and utilize BCAAs during substrate shortages. These findings support the proposed role of hGDH2 in astrocytes as an important fail-safe during situations of intense glutamatergic...

  16. Effects of Acute Exposure to Increased Plasma Branched-Chain Amino Acid Concentrations on Insulin-Mediated Plasma Glucose Turnover in Healthy Young Subjects

    OpenAIRE

    Sarah Everman; Mandarino, Lawrence J.; Carroll, Chad C.; Katsanos, Christos S.

    2015-01-01

    Background Plasma branched-chain amino acids (BCAA) are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity. Objective To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans. Methods Ten healthy subjects were randomly assigned to...

  17. Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups.

    Science.gov (United States)

    Martinez, Bridget; Soñanez-Organis, José G; Viscarra, Jose A; Jaques, John T; MacKenzie, Duncan S; Crocker, Daniel E; Ortiz, Rudy M

    2016-03-15

    Prolonged food deprivation in mammals typically reduces glucose, insulin, and thyroid hormone (TH) concentrations, as well as tissue deiodinase (DI) content and activity, which, collectively, suppress metabolism. However, in elephant seal pups, prolonged fasting does not suppress TH levels; it is associated with upregulation of adipose TH-mediated cellular mechanisms and adipose-specific insulin resistance. The functional relevance of this apparent paradox and the effects of glucose and insulin on TH-mediated signaling in an insulin-resistant tissue are not well defined. To address our hypothesis that insulin increases adipose TH signaling in pups during extended fasting, we assessed the changes in TH-associated genes in response to an insulin infusion in early- and late-fasted pups. In late fasting, insulin increased DI1, DI2, and THrβ-1 mRNA expression by 566%, 44%, and 267% at 60 min postinfusion, respectively, with levels decreasing by 120 min. Additionally, we performed a glucose challenge in late-fasted pups to differentiate between insulin- and glucose-mediated effects on TH signaling. In contrast to the insulin-induced effects, glucose infusion did not increase the expressions of DI1, DI2, and THrβ-1 until 120 min, suggesting that glucose delays the onset of the insulin-induced effects. The data also suggest that fasting duration increases the sensitivity of adipose TH-mediated mechanisms to insulin, some of which may be mediated by increased glucose. These responses appear to be unique among mammals and to have evolved in elephant seals to facilitate their adaptation to tolerate an extreme physiological condition. Copyright © 2016 the American Physiological Society.

  18. Dual phases of respiration chain defect-augmented mROS-mediated mCa 2+ stress during oxidative insult in normal and ρ 0 RBA1 astrocytes.

    Science.gov (United States)

    Peng, Tsung-I; Lin, Muh-Shi; Jou, Mei-Jie

    2013-01-01

    Mitochondrial respiratory chain (RC) deficits, resulting in augmented mitochondrial ROS (mROS) generation, underlie pathogenesis of astrocytes. However, mtDNA-depleted cells (ρ (0)) lacking RC have been reported to be either sensitive or resistant to apoptosis. In this study, we sought to determine the effects of RC-enhanced mitochondrial stress following oxidative insult. Using noninvasive fluorescence probe-coupled laser scanning imaging microscopy, the ability to resist oxidative stress and levels of mROS formation and mitochondrial calcium (mCa(2+)) were compared between two different astrocyte cell lines, control and ρ (0) astrocytes, over time upon oxidative stress. Our results showed that the cytoplasmic membrane becomes permeated with YO-PRO-1 dye at 150 and 130 minutes in RBA-1 and ρ (0) astrocytes, respectively. In contrast to RBA-1, 30 minutes after 20 mM H2O2 exposure, ρ (0) astrocytes formed marked plasma membrane blebs, lost the ability to retain Mito-R, and showed condensation of nuclei. Importantly, H2O2-induced ROS and accompanied mCa(2+) elevation in control showed higher levels than ρ (0) at early time point but vice versa at late time point. Our findings underscore dual phase of RC-defective cells harboring less mitochondrial stress due to low RC activity during short-term oxidative stress but augmented mROS-mediated mCa(2+) stress during severe oxidative insult.

  19. Dual Phases of Respiration Chain Defect-Augmented mROS-Mediated mCa2+ Stress during Oxidative Insult in Normal and ρ0 RBA1 Astrocytes

    Directory of Open Access Journals (Sweden)

    Tsung-I Peng

    2013-01-01

    Full Text Available Mitochondrial respiratory chain (RC deficits, resulting in augmented mitochondrial ROS (mROS generation, underlie pathogenesis of astrocytes. However, mtDNA-depleted cells (ρ0 lacking RC have been reported to be either sensitive or resistant to apoptosis. In this study, we sought to determine the effects of RC-enhanced mitochondrial stress following oxidative insult. Using noninvasive fluorescence probe-coupled laser scanning imaging microscopy, the ability to resist oxidative stress and levels of mROS formation and mitochondrial calcium (mCa2+ were compared between two different astrocyte cell lines, control and ρ0 astrocytes, over time upon oxidative stress. Our results showed that the cytoplasmic membrane becomes permeated with YO-PRO-1 dye at 150 and 130 minutes in RBA-1 and ρ0 astrocytes, respectively. In contrast to RBA-1, 30 minutes after 20 mM H2O2 exposure, ρ0 astrocytes formed marked plasma membrane blebs, lost the ability to retain Mito-R, and showed condensation of nuclei. Importantly, H2O2-induced ROS and accompanied mCa2+ elevation in control showed higher levels than ρ0 at early time point but vice versa at late time point. Our findings underscore dual phase of RC-defective cells harboring less mitochondrial stress due to low RC activity during short-term oxidative stress but augmented mROS-mediated mCa2+ stress during severe oxidative insult.

  20. Increased translocation of antigens to endosomes and TLR4 mediated endosomal recruitment of TAP contribute to nicotine augmented cross-presentation.

    Science.gov (United States)

    Wang, Yan Yan; Hu, Chun Fang; Li, Juan; You, Xiang; Gao, Feng Guang

    2016-06-21

    Cross-presentation by dendritic cells (DCs) requires surface molecules such as lectin, CD40, langerin, heat shock protein, mannose receptor, mediated endocytosis, the endosomal translocation of internalized antigen, and the relocation of transporter associated with antigen processing (TAP). Although the activation of α7 nicotinic acetylcholine receptor (α7 nAchR) up-regulate surface molecule expression, augment endocytosis, and enhance cross-presentation, the molecular mechanism of α7 nAchR activation-increased cross-presentation is still poorly understood. In this study, we investigated the role of mannose receptor in nicotine-increased cross-presentation and the mechanism that endotoxins orchestrating the recruitment of TAP toward endosomes. We demonstrated that nicotine increase the expressiones of mannose receptor and Toll-like receptor 4 (TLR4) via PI3K-Akt-mTOR-p70S6 pathway. Both endosomal translocation of mannose receptor-internalized antigens and TLR4 sig- naling are necessary for nicotine-augmented cross-presentation and cross-priming. Importantly, the recruitment of TAP toward endosomes via TLR4-MyD88-IRAK4 signaling contributes to nicotine-increased cross-presentation and cross-activation of T cells. Thus, these data suggest that increased recruitment of TAP to Ag-containing vesicles contributes to the superior cross-presentation efficacy of α7 nAchR activated DCs.

  1. Augmented activity of the pelvic nerve afferent mediated by TRP channels in dextran sulfate sodium (DSS)-induced colitis of rats.

    Science.gov (United States)

    Makimura, Yukitoshi; Ito, Koichi; Kuwahara, Masayoshi; Tsubone, Hirokazu

    2012-08-01

    Enteritis has been recognized as a major symptom in domestic animals and human patients suffering from feed and food poisonings. The aim of the present study was to clarify the excitatory mechanism of the pelvic nerve afferent which may influence the occurrence of enteritis in response to nociceptive chemical stimuli of the colon in normal and abnormal rats with colitis induced by dextran sulfate sodium (DSS). The pelvic nerve afferent activity was markedly increased by colonic instillation of solution (0.5 ml) of acetic acid (5-25%) and capsaicin (100 μg/ml). The nerve activity was augmented by colonic instillation of capsaicin to a greater extent in rats with DSS-induced colitis than in normal control rats. This augmented activity by capsaicin was more prominent at one day (DSS-1) than at 8 day (DSS-8) after the administration of DSS. The increased nerve activity caused by capsaicin in DSS-1 and DSS-8 was significantly inhibited by pretreatment with ruthenium red, which is a nonselective inhibitor of TRP channels of unmyelinated C-fibers (nociceptors). In conclusion, it was elucidated that the nociceptive function of the pelvic nerve was largely elevated at one day after DSS-induced colitis and such increased function was mostly mediated by TRP channels.

  2. Adr1 and Cat8 mediate coactivator recruitment and chromatin remodeling at glucose-regulated genes.

    Directory of Open Access Journals (Sweden)

    Rhiannon K Biddick

    Full Text Available BACKGROUND: Adr1 and Cat8 co-regulate numerous glucose-repressed genes in S. cerevisiae, presenting a unique opportunity to explore their individual roles in coactivator recruitment, chromatin remodeling, and transcription. METHODOLOGY/PRINCIPAL FINDINGS: We determined the individual contributions of Cat8 and Adr1 on the expression of a cohort of glucose-repressed genes and found three broad categories: genes that need both activators for full derepression, genes that rely mostly on Cat8 and genes that require only Adr1. Through combined expression and recruitment data, along with analysis of chromatin remodeling at two of these genes, ADH2 and FBP1, we clarified how these activators achieve this wide range of co-regulation. We find that Adr1 and Cat8 are not intrinsically different in their abilities to recruit coactivators but rather, promoter context appears to dictate which activator is responsible for recruitment to specific genes. These promoter-specific contributions are also apparent in the chromatin remodeling that accompanies derepression: ADH2 requires both Adr1 and Cat8, whereas, at FBP1, significant remodeling occurs with Cat8 alone. Although over-expression of Adr1 can compensate for loss of Cat8 at many genes in terms of both activation and chromatin remodeling, this over-expression cannot complement all of the cat8Delta phenotypes. CONCLUSIONS/SIGNIFICANCE: Thus, at many of the glucose-repressed genes, Cat8 and Adr1 appear to have interchangeable roles and promoter architecture may dictate the roles of these activators.

  3. Methanobactin-Mediated Synthesis of Gold Nanoparticles Supported over Al2O3 toward an Efficient Catalyst for Glucose Oxidation

    Directory of Open Access Journals (Sweden)

    Jia-Ying Xin

    2014-11-01

    Full Text Available Methanobactin (Mb is a copper-binding peptide that appears to function as an agent for copper sequestration and uptake in methanotrophs. Mb can also bind and reduce Au(III to Au(0. In this paper, Au/Al2O3 catalysts prepared by a novel incipient wetness-Mb-mediated bioreduction method were used for glucose oxidation. The catalysts were characterized, and the analysis revealed that very small gold nanoparticles with a particle size <4 nm were prepared by the incipient wetness-Mb-mediated bioreduction method, even at 1.0% Au loading (w/w. The influence of Au loading, calcination temperature and calcination time on the specific activity of Au/Al2O3 catalysts was systematically investigated. Experimental results showed that decomposing the Mb molecules properly by calcinations can enhance the specific activity of Au/Al2O3 catalysts, though they acted as reductant and protective agents during the catalyst preparation. Au/Al2O3 catalysts synthesized by the method exhibited optimum specific activity under operational synthesis conditions of Au loading of 1.0 wt % and calcined at 450 °C for 2 h. The catalysts were reused eight times, without a significant decrease in specific activity. To our knowledge, this is the first attempt at the preparation of Au/Al2O3 catalysts by Mb-mediated in situ synthesis of gold nanoparticles.

  4. Augmented Reality

    DEFF Research Database (Denmark)

    Kjærgaard, Hanne Wacher; Kjeldsen, Lars Peter Bech; Rahn, Annette

    2015-01-01

    This chapter describes the use of iPad-facilitated application of augmented reality in the teaching of highly complex anatomical and physiological subjects in the training of nurses at undergraduate level. The general aim of the project is to investigate the potentials of this application in terms...... of augmented reality are discussed....

  5. Augmented Reality

    DEFF Research Database (Denmark)

    Kjærgaard, Hanne Wacher; Kjeldsen, Lars Peter Bech; Rahn, Annette

    2015-01-01

    This chapter describes the use of iPad-facilitated application of augmented reality in the teaching of highly complex anatomical and physiological subjects in the training of nurses at undergraduate level. The general aim of the project is to investigate the potentials of this application in terms...... of augmented reality are discussed....

  6. Construction of Mutant Glucose Oxidases with Increased Dye-Mediated Dehydrogenase Activity

    Directory of Open Access Journals (Sweden)

    Koji Sode

    2012-11-01

    Full Text Available Mutagenesis studies on glucose oxidases (GOxs were conducted to construct GOxs with reduced oxidase activity and increased dehydrogenase activity. We focused on two representative GOxs, of which crystal structures have already been reported—Penicillium amagasakiense GOx (PDB ID; 1gpe and Aspergillus niger GOx (PDB ID; 1cf3. We constructed oxygen-interacting structural models for GOxs, and predicted the residues responsible for oxidative half reaction with oxygen on the basis of the crystal structure of cholesterol oxidase as well as on the fact that both enzymes are members of the glucose/methanol/choline (GMC oxidoreductase family. Rational amino acid substitution resulted in the construction of an engineered GOx with drastically decreased oxidase activity and increased dehydrogenase activity, which was higher than that of the wild-type enzyme. As a result, the dehydrogenase/oxidase ratio of the engineered enzyme was more than 11-fold greater than that of the wild-type enzyme. These results indicate that alteration of the dehydrogenase/oxidase activity ratio of GOxs is possible by introducing a mutation into the putative functional residues responsible for oxidative half reaction with oxygen of these enzymes, resulting in a further increased dehydrogenase activity. This is the first study reporting the alteration of GOx electron acceptor preference from oxygen to an artificial electron acceptor.

  7. Glucose starvation-mediated inhibition of salinomycin induced autophagy amplifies cancer cell specific cell death.

    Science.gov (United States)

    Jangamreddy, Jaganmohan R; Jain, Mayur V; Hallbeck, Anna-Lotta; Roberg, Karin; Lotfi, Kourosh; Łos, Marek J

    2015-04-30

    Salinomycin has been used as treatment for malignant tumors in a small number of humans, causing far less side effects than standard chemotherapy. Several studies show that Salinomycin targets cancer-initiating cells (cancer stem cells, or CSC) resistant to conventional therapies. Numerous studies show that Salinomycin not only reduces tumor volume, but also decreases tumor recurrence when used as an adjuvant to standard treatments. In this study we show that starvation triggered different stress responses in cancer cells and primary normal cells, which further improved the preferential targeting of cancer cells by Salinomycin. Our in vitro studies further demonstrate that the combined use of 2-Fluoro 2-deoxy D-glucose, or 2-deoxy D-glucose with Salinomycin is lethal in cancer cells while the use of Oxamate does not improve cell death-inducing properties of Salinomycin. Furthermore, we show that treatment of cancer cells with Salinomycin under starvation conditions not only increases the apoptotic caspase activity, but also diminishes the protective autophagy normally triggered by the treatment with Salinomycin alone. Thus, this study underlines the potential use of Salinomycin as a cancer treatment, possibly in combination with short-term starvation or starvation-mimicking pharmacologic intervention.

  8. Glucose deprivation induces reticulum stress by the PERK pathway and caspase-7- and calpain-mediated caspase-12 activation.

    Science.gov (United States)

    de la Cadena, Selene García; Hernández-Fonseca, Karla; Camacho-Arroyo, Ignacio; Massieu, Lourdes

    2014-03-01

    Glucose is the main energy source in brain and it is critical for correct brain functioning. Type 1 diabetic patients might suffer from severe hypoglycemia if exceeding insulin administration, which can lead to acute brain injury if not opportunely corrected. The mechanisms leading to hypoglycemic brain damage are not completely understood and the role of endoplasmic reticulum (ER) stress has not been studied. ER stress resulting from the accumulation of unfolded or misfolded proteins in the ER is counteracted by the unfolded protein response (UPR). When the UPR is sustained, apoptotic death might take place. We have examined UPR activation during glucose deprivation (GD) in hippocampal cultured neurons and its role in the induction of apoptosis. Activation of the PERK pathway of the UPR was observed, as increased phosphorylation of eIF2α and elevated levels of the transcription factor ATF4, occurred 30 min after GD and the levels of the chaperone protein, GRP78 and the transcription factor CHOP, increased after 2 h of GD. In addition, we observed an early activation of caspase-7 and 12 during GD, while caspase-3 activity increased only transiently during glucose reintroduction. Inhibition of caspase-3/7 and the calcium-dependent protease, calpain, significantly decreased caspase-12 activity. The ER stress inhibitor, salubrinal prevented neuronal death and caspase-12 activity. Results suggest that the PERK pathway of the UPR is involved in GD-induced apoptotic neuronal death through the activation of caspase-12, rather than the mitochondrial-dependent caspase pathway. In addition, we show that calpain and caspase-7 are soon activated after GD and mediate caspase-12 activation and neuronal death.

  9. Isoferulic Acid, a New Anti-Glycation Agent, Inhibits Fructose- and Glucose-Mediated Protein Glycation in Vitro

    Directory of Open Access Journals (Sweden)

    Sirichai Adisakwattana

    2013-05-01

    Full Text Available The inhibitory activity of isoferulic acid (IFA on fructose- and glucose-mediated protein glycation and oxidation of bovine serum albumin (BSA was investigated. Our data showed that IFA (1.25–5 mM inhibited the formation of fluorescent advanced glycation end products (AGEs and non-fluorescent AGE [Nε-(carboxymethyl lysine: CML], as well as the level of fructosamine. IFA also prevented protein oxidation of BSA indicated by decreasing protein carbonyl formation and protein thiol modification. Furthermore, IFA suppressed the formation of β-cross amyloid structures of BSA. Therefore, IFA might be a new promising anti-glycation agent for the prevention of diabetic complications via inhibition of AGEs formation and oxidation-dependent protein damage.

  10. The Performance of Electron-Mediator Modified Activated Carbon as Anode for Direct Glucose Alkaline Fuel Cell

    Directory of Open Access Journals (Sweden)

    Zi Li

    2016-06-01

    Full Text Available Six different electron mediators were immobilized on the activated carbon (AC anode and their effects on performance of a direct glucose alkaline fuel cell were explored. 2-hydroxy-1, 4-naphthoquinone (NQ, methyl viologen (MV, neutral red (NR, methylene blue (MB, 1, 5-dichloroanthraquinone (DA and anthraquinone (AQ were doped in activated carbon (AC, respectively, and pressed on nickel foam to fabricate the anodes. NQ shows comparable performance with MV, but with much lower cost and environmental impact. With NQ-AC anode, the fuel cell attained a peak power density of 16.10 Wm−2, peak current density of 48.09 Am−2, and open circuit voltage of 0.76 V under the condition of 1 M glucose, 3 M KOH, and ambient temperature. Polarization curve, EIS and Tafel measurements were also conducted to explore the mechanism of performance enhancement. The high performance is likely due to the enhanced charge transfer and more reactive sites provided on the anode.

  11. Crime Scenes as Augmented Reality

    DEFF Research Database (Denmark)

    Sandvik, Kjetil

    2010-01-01

    Using the concept of augmented reality, this article will investigate how places in various ways have become augmented by means of different mediatization strategies. Augmentation of reality implies an enhancement of the places' emotional character: a certain mood, atmosphere or narrative surplus......, physical damage: they are all readable and interpretable signs. As augmented reality the crime scene carries a narrative which at first is hidden and must be revealed. Due to the process of investigation and the detective's ability to reason and deduce, the crime scene as place is reconstructed as virtual...

  12. Crime Scenes as Augmented Reality

    DEFF Research Database (Denmark)

    Sandvik, Kjetil

    2010-01-01

    Using the concept of augmented reality, this article will investigate how places in various ways have become augmented by means of different mediatization strategies. Augmentation of reality implies an enhancement of the places' emotional character: a certain mood, atmosphere or narrative surplus......, physical damage: they are all readable and interpretable signs. As augmented reality the crime scene carries a narrative which at first is hidden and must be revealed. Due to the process of investigation and the detective's ability to reason and deduce, the crime scene as place is reconstructed as virtual...

  13. Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel.

    Science.gov (United States)

    Oya, Manami; Kitaguchi, Tetsuya; Harada, Kazuki; Numano, Rika; Sato, Takahiro; Kojima, Masayasu; Tsuboi, Takashi

    2015-07-01

    Ghrelin is synthesized in X/A-like cells of the gastric mucosa, which plays an important role in the regulation of energy homeostasis. Although ghrelin secretion is known to be induced by neurotransmitters or hormones or by nutrient sensing in the ghrelin-secreting cells themselves, the mechanism of ghrelin secretion is not clearly understood. In the present study, we found that changing the extracellular glucose concentration from elevated (25  mM) to optimal (10 mM) caused an increase in the intracellular Ca2+ concentration ([Ca2+]i) in ghrelin-secreting mouse ghrelinoma 3-1 (MGN3-1) cells (n=32, Pghrelin secretion (n≥3, Pghrelin secretion (n≥3, Pghrelin secretion (n≥5, Pghrelin secretion in MGN3-1 cells.

  14. The role of cysteine residues in glucose-transporter-GLUT1-mediated transport and transport inhibition.

    Science.gov (United States)

    Wellner, M; Monden, I; Keller, K

    1994-01-01

    The role of cysteine residues in transport function of the glucose transporter GLUT1 was investigated by a mutagenesis-expression strategy. Each of the six cysteine residues was individually replaced by site-directed mutagenesis. Expression of the heterologous wild-type or mutant glucose transporters and transport measurements at two hexose concentrations (50 microM and 5 mM) were undertaken in Xenopus oocytes. The catalytic activity of GLUT1 was retained, despite substitution of each single cysteine residue, which indicated that no individual residue is essential for hexose transport. This finding questions the involvement of oligomerization or intramolecular stabilization by a single disulphide bond as a prerequisite for transporter activation under basal conditions. Application of the impermeant mercurial thiol-group-reactive reagent p-chloromercuribenzenesulphonate (pCMBS) to the external or internal surface of plasma membrane demonstrated that cysteine-429, within the sixth external loop, and cysteine-207, at the beginning of the large intracellular loop which connects transmembrane segments 6 and 7, are the residues which are involved in transport inhibition by impermeant thiol-group-reactive reagents from either side of the cell. These data support the predicted membrane topology of the transport protein by transport measurements. If residues other than the cysteines at positions 429 or 207 are exposed to either side of the plasma membrane by conformational changes, they do not contribute to the transport inhibition by pCMBS. Application of pCMBS to one side of the plasma membrane also inhibited transport from the opposite direction, most likely due to the hindrance of sugar-induced interconversion of transporter conformation. PMID:8192671

  15. Augmented BMPRIA-mediated BMP signaling in cranial neural crest lineage leads to cleft palate formation and delayed tooth differentiation.

    Directory of Open Access Journals (Sweden)

    Lu Li

    Full Text Available The importance of BMP receptor Ia (BMPRIa mediated signaling in the development of craniofacial organs, including the tooth and palate, has been well illuminated in several mouse models of loss of function, and by its mutations associated with juvenile polyposis syndrome and facial defects in humans. In this study, we took a gain-of-function approach to further address the role of BMPR-IA-mediated signaling in the mesenchymal compartment during tooth and palate development. We generated transgenic mice expressing a constitutively active form of BmprIa (caBmprIa in cranial neural crest (CNC cells that contributes to the dental and palatal mesenchyme. Mice bearing enhanced BMPRIa-mediated signaling in CNC cells exhibit complete cleft palate and delayed odontogenic differentiation. We showed that the cleft palate defect in the transgenic animals is attributed to an altered cell proliferation rate in the anterior palatal mesenchyme and to the delayed palatal elevation in the posterior portion associated with ectopic cartilage formation. Despite enhanced activity of BMP signaling in the dental mesenchyme, tooth development and patterning in transgenic mice appeared normal except delayed odontogenic differentiation. These data support the hypothesis that a finely tuned level of BMPRIa-mediated signaling is essential for normal palate and tooth development.

  16. Furin mediates brain-derived neurotrophic factor upregulation in cultured rat astrocytes exposed to oxygen-glucose deprivation.

    Science.gov (United States)

    Chen, Yan; Zhang, Junjian; Deng, Min

    2015-01-01

    This study investigated the changes in brain-derived neurotrophic factor (BDNF) expression and the role of furin in BDNF maturation in reactive astrocytes from rats exposed to oxygen-glucose deprivation (OGD). Furin, a proprotein convertase, is upregulated and cleaves certain substrates during hypoxia in cancer cells. In addition, during hypoxia in the central nervous system, astrocytes become reactive and release BDNF to protect neurons. Maturation of BDNF in astrocytes requires furin-mediated endoproteolytic processing of the precursor protein pro-BDNF to BDNF. To expand our knowledge about the role of furin in BDNF maturation in astrocytes, these cells were exposed to OGD, and expression of furin and BDNF was detected by Western blot analysis. Changes in BDNF expression were observed when furin activity was inhibited by furin prosegment. We found that protein expression of BDNF and furin was upregulated, and this upregulation correlated with OGD stimulation. Furin inhibition reduced BDNF maturation and secretion. These results indicate that furin mediates the upregulation of BDNF in reactive astrocytes exposed to OGD and that furin may impact the biological effect of reactive astrocytes.

  17. Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus

    DEFF Research Database (Denmark)

    Nansen, A; Jensen, Teis; Christensen, Jan Pravsgaard

    1999-01-01

    -specific TCR are adoptively transferred before virus challenge, indicating that the disease is the result of an unfortunate balance between virus replication in internal organs, e.g., liver and spleen, and the host response; resetting this balance by increasing host responsiveness will again lead to a rapidly...... in wild-type mice. Our results reveal that IFN-gamma is pivotal to T cell-mediated control of a rapidly invasive stain, whereas it is less important in the acute elimination of a slowly invasive strain. Moreover, the majority of mice infected with the rapidly invasive strain succumb to a wasting syndrome...... mediated by CD8+ effector cells. The primary effector mechanism underlying this disease is perforin-dependent lysis, but other mechanisms are also involved. Wasting disease can be prevented if naive CD8+ cells from mice transgenic for an MHC class I-restricted lymphocytic choriomeningitis virus...

  18. Augmented reality

    National Research Council Canada - National Science Library

    Patrik Pucer

    2011-01-01

    .... In such a mixed reality, real and virtual objects coexist in the same environment. The reality, where users watch and use the real environment upgraded with virtual objects is called augmented reality...

  19. Breast Augmentation

    Science.gov (United States)

    ... surgery might even improve your body image and self-esteem. If you're looking for perfection, however, you ... www.mayoclinic.org/tests-procedures/breast-augmentation/basics/definition/prc-20021493 . Mayo Clinic Footer Legal Conditions and ...

  20. RhoB/ROCK mediates oxygen-glucose deprivation-stimulated syncytiotrophoblast microparticle shedding in preeclampsia.

    Science.gov (United States)

    Han, Jian; Yang, Bo-Ping; Li, Yi-Lin; Li, Hong-Mei; Zheng, Xiu-Hui; Yu, Li-Li; Zhang, Qiong; Zheng, Ying-Ru; Yi, Ping; Li, Li; Guo, Jian-Xin; Zhou, Yuan-Guo

    2016-11-01

    Increased circulating syncytiotrophoblast microparticles (STBMs) are often associated with preeclampsia (PE) but the molecular mechanisms regulating STBM shedding remain elusive. Experimental evidence has shown that actin plays a key role in STBM shedding and that Rho/ROCK is important in regulating actin rearrangement. To investigate the role of RhoB/ROCK-regulated actin arrangement in STBM shedding in PE, chorionic villous explants were prepared from placenta of patients with normotensive or PE pregnancies and BeWo cells were fused to imitate syncytiotrophoblasts. The oxygen-glucose deprivation (OGD) conditions were applied to imitate the pathophysiology of PE in vitro. The results showed that RhoB and ROCK were activated in the preeclamptic placenta, accompanied by increased actin polymerization and decreased outgrowing microvilli. In villous tissue cultures or BeWo cells, OGD activated RhoB, ROCK1 and ROCK2 and promoted STBM shedding and actin stress fibers formation. In BeWo cells, RhoB overexpression activated ROCK1 and ROCK2, leading to F-actin redistribution and STBM shedding and the OGD-induced actin polymerization and STBM shedding could be reversed by RhoB or ROCK knockdown. These results reveal that RhoB and ROCK play a key role in PE by targeting STBM shedding through actin rearrangement and that RhoB/ROCK intervention may be a potential therapeutic strategy for PE.

  1. Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis

    Science.gov (United States)

    Liu, T; Kishton, R J; Macintyre, A N; Gerriets, V A; Xiang, H; Liu, X; Abel, E D; Rizzieri, D; Locasale, J W; Rathmell, J C

    2014-01-01

    The metabolic profiles of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. In particular, a wide range of both solid and liquid tumors use aerobic glycolysis to supply energy and support cell growth. This metabolic program leads to high rates of glucose consumption through glycolysis with secretion of lactate even in the presence of oxygen. Identifying the limiting events in aerobic glycolysis and the response of cancer cells to metabolic inhibition is now essential to exploit this potential metabolic dependency. Here, we examine the role of glucose uptake and the glucose transporter Glut1 in the metabolism and metabolic stress response of BCR-Abl+ B-cell acute lymphoblastic leukemia cells (B-ALL). B-ALL cells were highly glycolytic and primary human B-ALL samples were dependent on glycolysis. We show B-ALL cells express multiple glucose transporters and conditional genetic deletion of Glut1 led to a partial loss of glucose uptake. This reduced glucose transport capacity, however, was sufficient to metabolically reprogram B-ALL cells to decrease anabolic and increase catabolic flux. Cell proliferation decreased and a limited degree of apoptosis was also observed. Importantly, Glut1-deficient B-ALL cells failed to accumulate in vivo and leukemic progression was suppressed by Glut1 deletion. Similarly, pharmacologic inhibition of aerobic glycolysis with moderate doses of 2-deoxyglucose (2-DG) slowed B-ALL cell proliferation, but extensive apoptosis only occurred at high doses. Nevertheless, 2-DG induced the pro-apoptotic protein Bim and sensitized B-ALL cells to the tyrosine kinase inhibitor Dasatinib in vivo. Together, these data show that despite expression of multiple glucose transporters, B-ALL cells are reliant on Glut1 to maintain aerobic glycolysis and anabolic metabolism. Further, partial inhibition of glucose metabolism is sufficient to sensitize cancer cells to specifically targeted therapies, suggesting

  2. Augmented reality

    Directory of Open Access Journals (Sweden)

    Patrik Pucer

    2011-08-01

    Full Text Available Today we can obtain in a simple and rapid way most of the information that we need. Devices, such as personal computers and mobile phones, enable access to information in different formats (written, pictorial, audio or video whenever and wherever. Daily we use and encounter information that can be seen as virtual objects or objects that are part of the virtual world of computers. Everyone, at least once, wanted to bring these virtual objects from the virtual world of computers into real environments and thus mix virtual and real worlds. In such a mixed reality, real and virtual objects coexist in the same environment. The reality, where users watch and use the real environment upgraded with virtual objects is called augmented reality. In this article we describe the main properties of augmented reality. In addition to the basic properties that define a reality as augmented reality, we present the various building elements (possible hardware and software that provide an insight into such a reality and practical applications of augmented reality. The applications are divided into three groups depending on the information and functions that augmented reality offers, such as help, guide and simulator.

  3. White light-mediated Cu (II)-5FU interaction augments the chemotherapeutic potential of 5-FU: an in vitro study.

    Science.gov (United States)

    Chibber, Sandesh; Farhan, Mohd; Hassan, Iftekhar; Naseem, Imrana

    2011-10-01

    5-Fluorouracil (5-FU) is a potent photosensitizer used in colon and rectal cancers. 5-FU on galvanostatic electrolysis or radiation-induced oxidation of aqueous solution yields N(1)-C(5)-linked dimmer hydrate of 5-FU. Copper is presently associated with chromatin; in cancer cells the concentration of copper is very high. It has been shown to be capable of mediating the action of several anticancer drugs through the production of reactive oxygen species (ROS). The objective of the present study is to determine the Cu (II)-mediated anticancer mechanism of 5-FU under photo-illumination as well as 5-FU alone. We have shown that a pro-oxidant action was enhanced when Cu (II) was used with 5-FU as compared to 5-FU alone. This may be due to the inhibition of dimerization of 5-FU when present in combination with Cu (II) under photo-illumination. It was also shown that 5-FU alone as well as in combination with Cu (II) was able to generate oxidative stress in lymphocyte which is inhibited by scavengers of ROS. Moreover, the results of Fourier-transformed infrared spectra lead to the conclusion that the dimerization of 5-FU was inhibited when used in combination with Cu (II). It was due to the interaction of 5-FU with Cu (II). Hence, we propose that during chemoradiotherapy with 5-FU, the endogenous copper is mobilized by 5-FU, leading to the generation of ROS which cause oxidative stress and possibly cancer cell death by apoptosis.

  4. Computational Analysis of AMPK-Mediated Neuroprotection Suggests Acute Excitotoxic Bioenergetics and Glucose Dynamics Are Regulated by a Minimal Set of Critical Reactions.

    Directory of Open Access Journals (Sweden)

    Niamh M C Connolly

    Full Text Available Loss of ionic homeostasis during excitotoxic stress depletes ATP levels and activates the AMP-activated protein kinase (AMPK, re-establishing energy production by increased expression of glucose transporters on the plasma membrane. Here, we develop a computational model to test whether this AMPK-mediated glucose import can rapidly restore ATP levels following a transient excitotoxic insult. We demonstrate that a highly compact model, comprising a minimal set of critical reactions, can closely resemble the rapid dynamics and cell-to-cell heterogeneity of ATP levels and AMPK activity, as confirmed by single-cell fluorescence microscopy in rat primary cerebellar neurons exposed to glutamate excitotoxicity. The model further correctly predicted an excitotoxicity-induced elevation of intracellular glucose, and well resembled the delayed recovery and cell-to-cell heterogeneity of experimentally measured glucose dynamics. The model also predicted necrotic bioenergetic collapse and altered calcium dynamics following more severe excitotoxic insults. In conclusion, our data suggest that a minimal set of critical reactions may determine the acute bioenergetic response to transient excitotoxicity and that an AMPK-mediated increase in intracellular glucose may be sufficient to rapidly recover ATP levels following an excitotoxic insult.

  5. Oat β-glucan depresses SGLT1- and GLUT2-mediated glucose transport in intestinal epithelial cells (IEC-6).

    Science.gov (United States)

    Abbasi, Nazanin N; Purslow, Peter P; Tosh, Susan M; Bakovic, Marica

    2016-06-01

    Oat β-glucan consumption is linked to reduced risk factors associated with diabetes and obesity by lowering glycemic response and serum level of low-density lipoproteins. The purpose of this study was to identify the mechanism of action of oat β-glucan at the interface between the gut wall and the lumen responsible for attenuating glucose levels. We proposed that viscous oat β-glucan acts as a physical barrier to glucose uptake in normally absorptive gut epithelial cells IEC-6 by affecting the expression of intestinal glucose transporters. Concentration and time-dependent changes in glucose uptake were established by using a nonmetabolizable glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose. The effectiveness of nutrient transport in IEC-6 cells was shown by significant differences in glucose uptake and corresponding transporter expression. The expressions of glucose transporters sodium-glucose-linked transport protein 1 (SGLT1) and glucose transporter 2 (GLUT2) increased with time (0-60 minutes) and glucose levels (5-25 mmol/L). The suppression of glucose uptake and SGLT1 and GLUT2 expression by increasing concentrations (4-8 mg/mL) of oat β-glucan demonstrated a direct effect of the physical properties of oat β-glucan on glucose transport. These results affirmed oat β-glucan as a dietary agent for minimizing postprandial glucose and showed that modulating the activity of the key intestinal glucose transporters with oat β-glucan could be an effective way of lowering blood glucose levels in patients with diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Regulation of GLUT1-mediated glucose uptake by PKClambda-PKCbeta(II) interactions in 3T3-L1 adipocytes.

    NARCIS (Netherlands)

    Bosch, R.R.; Bazuine, M.; Span, P.N.; Willems, P.H.G.M.; Olthaar, A.J.; Rennes, H. van; Maassen, J.A.; Tack, C.J.J.; Hermus, A.R.M.M.; Sweep, C.G.J.

    2004-01-01

    Members of the PKC (protein kinase C) superfamily play key regulatory roles in glucose transport. How the different PKC isotypes are involved in the regulation of glucose transport is still poorly defined. PMA is a potent activator of conventional and novel PKCs and PMA increases the rate of glucose

  7. The impact of dipeptidyl peptidase 4 inhibition on incretin effect, glucose tolerance, and gastrointestinal-mediated glucose disposal in healthy subjects

    DEFF Research Database (Denmark)

    Rhee, Nicolai Alexander; Østoft, Signe Harring; Holst, Jens Juul

    2014-01-01

    /mol [5.3±0.1%]) were randomised to two paired study days comprising a 4h 50 g-OGTT with paracetamol (A) and an isoglycaemic i.v. glucose infusion (IIGI) (B), with (A1+B1) and without (A2+B2) preceding administration of the DPP-4 inhibitor sitagliptin. Results Isoglycaemia was obtained in all subjects...... gastric emptying (Tmax for plasma paracetamol: 86±9 vs 80±12 min, p=0.60) changed following DPP-4 inhibition. Conclusions These results suggest that acute increases in active incretin hormone levels do not affect glucose tolerance, GIGD, incretin effect, glucagon responses or gastric emptying in healthy...

  8. Annexin-1 Mediates Microglial Activation and Migration via the CK2 Pathway during Oxygen–Glucose Deprivation/Reperfusion

    Directory of Open Access Journals (Sweden)

    Shuangxi Liu

    2016-10-01

    Full Text Available Annexin-1 (ANXA1 has shown neuroprotective effects and microglia play significant roles during central nervous system injury, yet the underlying mechanisms remain unclear. This study sought to determine whether ANXA1 regulates microglial response to oxygen–glucose deprivation/reperfusion (OGD/R treatment and to clarify the downstream molecular mechanism. In rat hippocampal slices, OGD/R treatment enhanced the ANXA1 expression in neuron, the formyl peptide receptor (FPRs expression in microglia, and the microglial activation in the CA1 region (cornu ammonis 1. These effects were reversed by the FPRs antagonist Boc1. The cell membrane currents amplitude of BV-2 microglia (the microglial like cell-line was increased when treated with Ac2-26, the N-terminal peptide of ANXA1. Ac2-26 treatment enhanced BV-2 microglial migration whereas Boc1 treatment inhibited the migration. In BV-2 microglia, both the expression of the CK2 target phosphorylated α-E-catenin and the binding of casein kinase II (CK2 with α-E-catenin were elevated by Ac2-26, these effects were counteracted by the CK2 inhibitor TBB and small interfering (si RNA directed against transcripts of CK2 and FPRs. Moreover, both TBB and siRNA-mediated inhibition of CK2 blocked Ac2-26-mediated BV-2 microglia migration. Our findings indicate that ANXA1 promotes microglial activation and migration during OGD/R via FPRs, and CK2 target α-E-catenin phosphorylation is involved in this process.

  9. Augmenting Clozapine With Sertindole

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Emborg, Charlotte; Gydesen, Susanne

    2012-01-01

    randomized 1:1 to either sertindole 16 mg or placebo, and assessment was done at baseline and after 6 and 12 weeks. Assessment included the Positive and Negative Syndrome Scale, Clinical Global Impression, Udvalg for Kliniske Undersøgelser, World Health Organization Quality of Life Brief, Drug Attitude...... Inventory, fasting glucose, lipids, and electrocardiogram. Clozapine augmentation with sertindole was not superior to placebo regarding total score or subscale score of the Positive and Negative Syndrome Scale, Clinical Global Impression, World Health Organization Quality of Life Brief, or Drug Attitude...

  10. Picture Exchange Communication System and Pals: A Peer-Mediated Augmentative and Alternative Communication Intervention for Minimally Verbal Preschoolers With Autism.

    Science.gov (United States)

    Thiemann-Bourque, Kathy; Brady, Nancy; McGuff, Sara; Stump, Keenan; Naylor, Amy

    2016-10-01

    This study was conducted to investigate the effectiveness of a social intervention that integrates peer-mediated approaches and the Picture Exchange Communication System (PECS). Effects were evaluated using a series of A-B designs replicated across 4 children with severe autism and limited verbal skills. Seven peers without disabilities were trained to use PECS and facilitative social skills. Measures of changes included rates of communication behaviors, modes, functions, and engagement. Outcomes revealed an intervention effect for 1 child with autism, and this effect was replicated across 3 other children. All children improved in peer-directed communication, with greater increases for 2 children during snack time. For each child with autism, the primary communication behavior was to initiate with picture symbols to request; the peer's primary communication was to respond. Two children increased communicative functions to comment and to share, and all 4 children showed improved social engagement. All peers increased their communication with the children with autism. These findings add to the limited research on the benefits of teaching typically developing peers to be responsive listeners to preschoolers with autism by learning to use PECS. These results invite further investigation of teaching peers other augmentative and alternative communication approaches and how to increase children's communication with peers for different purposes.

  11. Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects.

    Directory of Open Access Journals (Sweden)

    Sarah Everman

    Full Text Available Plasma branched-chain amino acids (BCAA are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity.To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans.Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5 to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5. In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U in association with the above BCAA infusion (N = 4 or under the same conditions without BCAA infusion (N = 3. Plasma glucose turnover was measured prior to and during insulin infusion.Insulin infusion completely suppressed the endogenous glucose production (EGP across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05. Insulin infusion stimulated whole-body glucose disposal rate (GDR across all groups. However, the increase (% in GDR was not different [median (1st quartile - 3rd quartile] between Control and BCAA in either the 40U ([199 (167-278 vs. 186 (94-308] or 80 U ([491 (414-548 vs. 478 (409-857] experiments (P > 0.05. Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P 0.05.Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

  12. Augmented Reality

    DEFF Research Database (Denmark)

    Nielsen, Birgitte Lund; Brandt, Harald; Radmer, Ole

    2017-01-01

    Artiklen præsenterer resultater fra pilotafprøvning i 7.-klasses fysik/kemi og biologi af to Augmented Reality (AR)-apps til naturfagsundervisning. Muligheder og udfordringer ved lærerens stilladsering af elevernes undersøgende samtale og modelleringskompetence er undersøgt med interview...

  13. Augmented Reality

    DEFF Research Database (Denmark)

    Kjærgaard, Hanne Wacher; Kjeldsen, Lars Peter Bech; Rahn, Annette

    2015-01-01

    This chapter describes the use of iPad-facilitated application of augmented reality in the teaching of highly complex anatomical and physiological subjects in the training of nurses at undergraduate level. The general aim of the project is to investigate the potentials of this application in term...

  14. CaV3.2 T-type Ca2+ channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia.

    Science.gov (United States)

    Makarenko, Vladislav V; Ahmmed, Gias U; Peng, Ying-Jie; Khan, Shakil A; Nanduri, Jayasri; Kumar, Ganesh K; Fox, Aaron P; Prabhakar, Nanduri R

    2016-01-01

    Chronic intermittent hypoxia (CIH) is a hallmark manifestation of sleep apnea. A heightened carotid body activity and the resulting chemosensory reflex mediate increased sympathetic nerve activity by CIH. However, the mechanisms underlying heightened carotid body activity by CIH are not known. An elevation of intracellular calcium ion concentration ([Ca(2+)]i) in glomus cells, the primary oxygen-sensing cells, is an essential step for carotid body activation by hypoxia. In the present study, we examined the effects of CIH on the glomus cell [Ca(2+)]i response to hypoxia and assessed the underlying mechanisms. Glomus cells were harvested from adult rats or wild-type mice treated with 10 days of either room air (control) or CIH (alternating cycles of 15 s of hypoxia and 5 min of room air; 9 episodes/h; 8 h/day). CIH-treated glomus cells exhibited an enhanced [Ca(2+)]i response to hypoxia, and this effect was absent in the presence of 2-(4-cyclopropylphenyl)-N-((1R)-1-[5-[(2,2,2-trifluoroethyl)oxo]-pyridin-2-yl]ethyl)acetamide (TTA-A2), a specific inhibitor of T-type Ca(2+) channels, and in voltage-gated calcium channel, type 3.2 (CaV3.2), null glomus cells. CaV3.2 knockout mice exhibited an absence of CIH-induced hypersensitivity of the carotid body. CIH increased reactive oxygen species (ROS) levels in glomus cells. A ROS scavenger prevented the exaggerated TTA-A2-sensitive [Ca(2+)]i response to hypoxia. CIH had no effect on CaV3.2 mRNA levels. CIH augmented Ca(2+) currents and increased CaV3.2 protein in plasma membrane fractions of human embryonic kidney-293 cells stably expressing CaV3.2, and either a ROS scavenger or brefeldin-A, an inhibitor of protein trafficking, prevented these effects. These findings suggest that CIH leads to an augmented Ca(2+) influx via ROS-dependent facilitation of CaV3.2 protein trafficking to the plasma membrane.

  15. Neuroprotection of phenolic alkaloids from Menispermum dauricum versus melatonin against oxygen-glucose-serum-deprivation-mediated injury

    Institute of Scientific and Technical Information of China (English)

    Zhongqiang Wang; Jianfei Wang; Yanchun Guo; Tao Lu; Ximing Wang; Qiuhong Duan

    2009-01-01

    BACKGROUND: Recent studies have demonstrated that phenolic alkaloids from Menispermum dauricum (PAMD) can protect the heart and brain from ischemia/reperfusion injury, and promote neuron survival by inhibiting neuronal Bax and upregulating Bcl-2 expression following ischemia/reperfusion. OBJECTIVE: To investigate the neuroprotective effects of PAMD versus exogenous melatonin against ischemia/reperfusion injury. DESIGN, TIME AND SETTING: Observation and comparison experiments at a cellular level were performed at the Department of Biochemistry and Molecular Biology, Tongji Medical College of Huazhong University of Science and Technology between February 2007 and February 2008.MATERIALS: PAMD (95% purity) was provided by Kunming Institute of Botany, Chinese Academy of Sciences; melatonin was provided by Sigma, USA.METHODS: N2a mouse neuroblastoma cells were cultured in vitro deprived of glucose, serum and oxygen for 90 minutes, then cultured in normal medium containing different concentrations of PAMD (0.1, 1.0, 10 mg/L) or melatonin (1, 10, and 100 μmol/L). Cells cultured in normal conditions served as a control. MAIN OUTCOME MEASURES: The culture solution was collected to determine the content of excitatory neurotransmitters such as glutamic acid and aspartic acid; cell viability was detected by MTT methods; reactive oxygen species production was determined by fluorescence spectroscopy; mitochondrial transmembrane potential (?Ψm) was detected by laser confocal scanning; cytochrome C was measured by western blotting; and caspase-3 activity was determined by visible spectrophotometry. RESULTS: Melatonin and PAMD both promoted oxygen-glucose-serum deprivation-mediated N2a cell survival (P < 0.01) and inhibited glutamic acid release (P < 0.01), but melatonin did not inhibit aspartic acid production. The protective effects were the strongest using melatonin 100 μmol/L and PAMD 10 mg/L, so subsequent experiments were the performed at those doses. Although PAMD could

  16. Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms.

    Directory of Open Access Journals (Sweden)

    Helen N Jones

    Full Text Available Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor -1 (hIGF-1 in the placenta corrects fetal weight deficits in mouse, rat, and rabbit models of intrauterine growth restriction without changes in placental weight. The underlying mechanisms of this effect have not been elucidated. To investigate the effect of intra-placental IGF-1 over-expression on placental function we examined glucose transporter expression and localization in both a mouse model of IUGR and a model of human trophoblast, the BeWo Choriocarcinoma cell line.At gestational day 18, animals were divided into four groups; sham-operated controls, uterine artery branch ligation (UABL, UABL+Ad-hIGF-1 (10(8 PFU, UABL+Ad-LacZ (10(8 PFU. At gestational day 20, pups and placentas were harvested by C-section. For human studies, BeWo choriocarcinoma cells were grown in F12 complete medium +10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 hours. MOIs of 10∶1 and 100∶1 were utilized. The RNA, protein expression and localization of glucose transporters GLUT1, 3, 8, and 9 were analyzed by RT-PCR, Western blot and immunohistochemistry.In both the mouse placenta and BeWo, GLUT1 regulation was linked to altered protein localization. GLUT3, localized to the mouse fetal endothelial cells, was reduced in placental insufficiency but maintained with Ad-I GF-1 treatment. Interestingly, GLUT8 expression was reduced in the UABL placenta but up-regulated following Ad-IGF-1 in both mouse and human systems. GLUT9 expression in the mouse was increased by Ad-IGF-1 but this was not reflected in the BeWo, where Ad-IGF-1 caused moderate membrane relocalization.Enhanced GLUT isoform transporter expression and relocalization to the membrane may be an important mechanism in Ad-hIGF-1mediated correction of placental insufficiency.

  17. Hepatic branch vagus nerve plays a critical role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A.

    Science.gov (United States)

    Harada, Shinichi; Yamazaki, Yui; Koda, Shuichi; Tokuyama, Shogo

    2014-01-01

    Orexin-A (a neuropeptide in the hypothalamus) plays an important role in many physiological functions, including the regulation of glucose metabolism. We have previously found that the development of post-ischemic glucose intolerance is one of the triggers of ischemic neuronal damage, which is suppressed by hypothalamic orexin-A. Other reports have shown that the communication system between brain and peripheral tissues through the autonomic nervous system (sympathetic, parasympathetic and vagus nerve) is important for maintaining glucose and energy metabolism. The aim of this study was to determine the involvement of the hepatic vagus nerve on hypothalamic orexin-A-mediated suppression of post-ischemic glucose intolerance development and ischemic neuronal damage. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Intrahypothalamic orexin-A (5 pmol/mouse) administration significantly suppressed the development of post-ischemic glucose intolerance and neuronal damage on day 1 and 3, respectively after MCAO. MCAO-induced decrease of hepatic insulin receptors and increase of hepatic gluconeogenic enzymes on day 1 after was reversed to control levels by orexin-A. This effect was reversed by intramedullary administration of the orexin-1 receptor antagonist, SB334867, or hepatic vagotomy. In the medulla oblongata, orexin-A induced the co-localization of cholin acetyltransferase (cholinergic neuronal marker used for the vagus nerve) with orexin-1 receptor and c-Fos (activated neural cells marker). These results suggest that the hepatic branch vagus nerve projecting from the medulla oblongata plays an important role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A.

  18. Hepatic branch vagus nerve plays a critical role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A.

    Directory of Open Access Journals (Sweden)

    Shinichi Harada

    Full Text Available Orexin-A (a neuropeptide in the hypothalamus plays an important role in many physiological functions, including the regulation of glucose metabolism. We have previously found that the development of post-ischemic glucose intolerance is one of the triggers of ischemic neuronal damage, which is suppressed by hypothalamic orexin-A. Other reports have shown that the communication system between brain and peripheral tissues through the autonomic nervous system (sympathetic, parasympathetic and vagus nerve is important for maintaining glucose and energy metabolism. The aim of this study was to determine the involvement of the hepatic vagus nerve on hypothalamic orexin-A-mediated suppression of post-ischemic glucose intolerance development and ischemic neuronal damage. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO for 2 h. Intrahypothalamic orexin-A (5 pmol/mouse administration significantly suppressed the development of post-ischemic glucose intolerance and neuronal damage on day 1 and 3, respectively after MCAO. MCAO-induced decrease of hepatic insulin receptors and increase of hepatic gluconeogenic enzymes on day 1 after was reversed to control levels by orexin-A. This effect was reversed by intramedullary administration of the orexin-1 receptor antagonist, SB334867, or hepatic vagotomy. In the medulla oblongata, orexin-A induced the co-localization of cholin acetyltransferase (cholinergic neuronal marker used for the vagus nerve with orexin-1 receptor and c-Fos (activated neural cells marker. These results suggest that the hepatic branch vagus nerve projecting from the medulla oblongata plays an important role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A.

  19. Effects of endogenous androgens and abdominal fat distribution on the interrelationship between insulin and non-insulin-mediated glucose uptake in females.

    Science.gov (United States)

    Ezeh, Uche; Pall, Marita; Mathur, Ruchi; Dey, Damini; Berman, Daniel; Chen, Ida Y; Dumesic, Daniel A; Azziz, Ricardo

    2013-04-01

    Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance. Glucose disposal occurs via noninsulin-mediated glucose uptake (NIMGU) and insulin-mediated glucose uptake (IMGU). It is unknown whether in PCOS NIMGU increases to compensate for declining IMGU and whether androgens and fat distribution influence this relationship. The objective of the study was to compare in women with PCOS and controls the interrelationship between NIMGU [ie, glucose effectiveness (Sg)] and IMGU [ie, the insulin sensitivity index (Si)] and the role of androgens and fat distribution. Twenty-eight PCOS (by National Institutes of Health 1990 criteria) and 28 control (age, race, and body mass index matched) women were prospectively studied. A subset of 16 PCOS subjects and 16 matched controls also underwent abdominal computed tomography. Glucose disposal (by a frequently sampled iv glucose tolerance test), circulating androgens, and abdominal fat distribution [by waist to hip ratio and visceral (VAT) and sc (SAT) adipose tissue content] were measured. PCOS women had lower mean Si and similar Sg and abdominal fat distribution compared with controls. PCOS women with Si below the PCOS median (more insulin resistant) had a lower mean Sg than controls with Si above the control median (more insulin sensitive). In PCOS only, body mass index, free T, modified Ferriman-Gallwey score, and waist to hip ratio independently predicted Sg, whereas Si did not. In PCOS, VAT and SAT independently and negatively predicted Si and Sg, respectively. The decreased IMGU in PCOS is not accompanied by a compensatory increase in NIMGU or associated with excessive VAT accumulation. Increased general obesity, SAT, and hyperandrogenism are primary predictors of the deterioration of NIMGU in PCOS.

  20. ChREBP Mediates Glucose Repression of Peroxisome Proliferator-activated Receptor {alpha} Expression in Pancreatic {beta}-Cells

    DEFF Research Database (Denmark)

    Boergesen, Michael; Poulsen, Lars la Cour; Schmidt, Søren Fisker;

    2011-01-01

    Chronic exposure to elevated levels of glucose and fatty acids leads to dysfunction of pancreatic β-cells by mechanisms that are only partly understood. The transcription factor peroxisome proliferator-activated receptor α (PPARα) is an important regulator of genes involved in fatty acid metaboli...... of glucose repression of PPARα gene expression in pancreatic β-cells, suggesting that ChREBP may be important for glucose suppression of the fatty acid oxidation capacity of β-cells....

  1. Ginkgolide B Suppresses TLR4-Mediated Inflammatory Response by Inhibiting the Phosphorylation of JAK2/STAT3 and p38 MAPK in High Glucose-Treated HUVECs

    Directory of Open Access Journals (Sweden)

    Kun Chen

    2017-01-01

    Full Text Available Aim. Ginkgolide B is a Ginkgo biloba leaf extract that has been identified as a natural platelet-activating factor receptor (PAFR antagonist. We investigated the effect of ginkgolide B on high glucose-induced TLR4 activation in human umbilical vein endothelial cells (HUVECs. Methods. Protein expression was analyzed by immunoblotting. Small-interfering RNA (siRNA was used to knock down PAFR and TLR4 expression. Results. Ginkgolide B suppressed the expression of TLR4 and MyD88 that was induced by high glucose. Ginkgolide B also reduced the levels of platelet endothelial cell adhesion molecule-1, interleukin-6, and monocyte chemotactic protein 1. Further, we examined the association between PAFR and TLR4 by coimmunoprecipitation. The result showed that high glucose treatment caused the binding of PAFR and TLR4, whereas ginkgolide B abolished this binding. The functional analysis indicated that PAFR siRNA treatment reduced TLR4 expression, and TLR4 siRNA treatment decreased PAFR expression in high glucose-treated HUVECs, further supporting the coimmunoprecipitation data. Ginkgolide B inhibited the phosphorylation of Janus kinase 2 (JAK2/signal transducer and activator of transcription 3 (STAT3 and p38 mitogen-activated protein kinase (MAPK. Conclusion. Ginkgolide B exerted protective effects by inhibiting the TLR4-mediated inflammatory response in high glucose-treated endothelial cells. The mechanism of action of ginkgolide B might be associated with inhibition of the JAK2/STAT3 and p38 MAPK phosphorylation.

  2. Glucose-stimulated insulin secretion does not require activation of pyruvate dehydrogenase: impact of adenovirus-mediated overexpression of PDH kinase and PDH phosphate phosphatase in pancreatic islets.

    Science.gov (United States)

    Nicholls, Linda I; Ainscow, Edward K; Rutter, Guy A

    2002-03-01

    Glucose-stimulated increases in mitochondrial metabolism are generally thought to be important for the activation of insulin secretion. Pyruvate dehydrogenase (PDH) is a key regulatory enzyme, believed to govern the rate of pyruvate entry into the citrate cycle. We show here that elevated glucose concentrations (16 or 30 vs 3 mM) cause an increase in PDH activity in both isolated rat islets, and in a clonal beta-cell line (MIN6). However, increases in PDH activity elicited with either dichloroacetate, or by adenoviral expression of the catalytic subunit of pyruvate dehydrogenase phosphatase, were without effect on glucose-induced increases in mitochondrial pyridine nucleotide levels, or cytosolic ATP concentration, in MIN6 cells, and insulin secretion from isolated rat islets. Similarly, the above parameters were unaffected by blockade of the glucose-induced increase in PDH activity by adenovirus-mediated over-expression of PDH kinase (PDK). Thus, activation of the PDH complex plays an unexpectedly minor role in stimulating glucose metabolism and in triggering insulin release.

  3. Augmented Reality

    DEFF Research Database (Denmark)

    Arusoaie, Andrei; Cristei, Alexandru Ionuţ; Chircu, Cristian

    2011-01-01

    applications. In the first section the focus is set on the Augmented Reality basic concepts and the necessity of developing such a framework. The prototype that we present in the second part of this paper comes to demonstrate how our framework can be used to achieve our targeted application for Augmented......Virtual Reality is becoming more than a part of our everyday life, helping us to identify quickly the elements of the environment or to better entertain us. The purpose of this paper is to present an application framework that we are developing, in order to help others implement their own...... Reality. It also contains some future works to highlight the capabilities of the AR API. © 2010 IEEE....

  4. Reductions in laminin beta2 mRNA translation are responsible for impaired IGFBP-5-mediated mesangial cell migration in the presence of high glucose.

    Science.gov (United States)

    Schaeffer, Valerie; Hansen, Kim M; Morris, David R; Abrass, Christine K

    2010-02-01

    Insulin-like growth factor binding protein-5 (IGFBP-5) mediates mesangial cell migration through activation of cdc42, and laminin421 binding to alpha(6)beta(1)-integrin (Berfield AK, Hansen KM, Abrass CK. Am J Physiol Cell Physiol 291: C589-C599, 2006). Because glomerular expression of laminin beta(2) is reduced in diabetic rats (Abrass CK, Spicer D, Berfield AK, St. John PL, Abrahamson DR. Am J Pathol 151: 1131-1140, 1997), we directly examined the effect of hyperglycemia on mesangial cell migration and laminin beta2 expression. Migration mediated by IGFBP-5 is impaired in the presence of 25 mM glucose. This reduction in migration was found to result from a loss in mesangial cell synthesis of laminin421, and IGFBP-5-induced migration could be restored by replacing laminin421. Additional studies showed that there was selective reduction in mRNA translation of laminin beta2 in the presence of high glucose. Preserved synthesis of laminin beta1 indicates that not all proteins are reduced by high glucose and confirms prior data showing that laminin411 cannot substitute for laminin421 in IGFBP-5-mediated migration. Given the importance of mesangial migration in the reparative response to diabetes-associated mesangiolysis, these findings provide new insights into abnormalities associated with diabetic nephropathy and the potential importance of differential control of protein translation in determination of alterations of protein expression.

  5. Differential role of hydrogen peroxide and organic hydroperoxides in augmenting ferric nitrilotriacetate (Fe-NTA)-mediated DNA damage: implications for carcinogenesis.

    Science.gov (United States)

    Iqbal, Mohammad; Sharma, Som Datta; Mizote, Akiko; Fujisawa, Masayoshi; Okada, Shigeru

    2003-01-01

    An iron chelate, ferric nitrilotriacetate (Fe-NTA), is a potent nephrotoxic agent, and induces acute and subacute renal proximal tubular necrosis, a consequence of the Fenton-like reaction that eventually leads to a high incidence of renal adenocarcinoma in rodents. In order to examine the possible mechanism for carcinogenic activity, we investigated the DNA damage with Fe-NTA in the presence of various peroxides/organic hydroperoxides. S1 nuclease hydrolysis and deoxyribose degradation assays were performed. Incubation of calf thymus DNA with ferric nitrilotriacetate (0.1 mM) in the presence of peroxides/organic hydroperoxides at a final concentration of 40 mM of each in phosphate buffer (0.1 M, pH 7.4) augmented DNA damage severalfold as compared to the damage caused by individual treatments. Fe-NTA in the presence of hydrogen peroxide caused DNA single-strand breaks and damage to its deoxyribose sugar moiety as measured, respectively, by S1 nuclease hydrolysis and deoxyribose degradation using calf thymus DNA. However, only deoxyribose degradation could be recorded in the presence of other peroxide/organic hydroperoxides. No DNA single-strand break was observed by this treatment. The observed differences in DNA damage by hydrogen peroxide and organic hydroperoxides/peroxide have been ascribed to the differential reactivity of DNA with hydroxyl and alkoxy/aryloxy free radicals produced, respectively, from these inorganic and organic peroxides. These studies suggest that Fe-NTA not only mediated the production of reactive oxygen species, but also catalysed the decomposition of these peroxides and organic hydroperoxides, which may cause a clastogenic change in DNA. This reactivity enhances the clastogenic activity in DNA. These changes in the DNA structure may ultimately be responsible, at least in part, for the induction of carcinogenesis in Fe-NTA-exposed animals.

  6. The pancreatic beta cell is a key site for mediating the effects of leptin on glucose homeostasis.

    Science.gov (United States)

    Covey, Scott D; Wideman, Rhonda D; McDonald, Christine; Unniappan, Suraj; Huynh, Frank; Asadi, Ali; Speck, Madeleine; Webber, Travis; Chua, Streamson C; Kieffer, Timothy J

    2006-10-01

    The hormone leptin plays a crucial role in maintenance of body weight and glucose homeostasis. This occurs through central and peripheral pathways, including regulation of insulin secretion by pancreatic beta cells. To study this further in mice, we disrupted the signaling domain of the leptin receptor gene in beta cells and hypothalamus. These mice develop obesity, fasting hyperinsulinemia, impaired glucose-stimulated insulin release, and glucose intolerance, similar to leptin receptor null mice. However, whereas complete loss of leptin function causes increased food intake, this tissue-specific attenuation of leptin signaling does not alter food intake or satiety responses to leptin. Moreover, unlike other obese models, these mice have reduced fasting blood glucose. These results indicate that leptin regulation of glucose homeostasis extends beyond insulin sensitivity to influence beta cell function, independent of pathways controlling food intake. These data suggest that defects in this adipoinsular axis could contribute to diabetes associated with obesity.

  7. Differences in the involvement of prostanoids from Kupffer cells in the mediation of anaphylatoxin C5a-, zymosan-, and lipopolysaccharide-dependent hepatic glucose output and flow reduction.

    Science.gov (United States)

    Pestel, Sabine; Schlaf, Gerald; Götze, Otto; Jungermann, Kurt; Schieferdecker, Henrike L

    2003-12-01

    Various inflammatory stimuli such as anaphylatoxin C5a, zymosan, and lipopolysaccharides (LPSs) have been reported both to enhance glucose output in the perfused rat liver and to induce prostanoid (ie, prostaglandin and thromboxane) release from Kupffer cells, the resident liver macrophages. Because prostanoids can enhance glucose output from hepatocytes, it was the aim of this study to compare the possible roles of prostanoids released after C5a, zymosan, and LPS in the mediation of hepatic glucose output. In perfused livers both C5a and zymosan immediately enhanced glucose output, reduced flow, and induced prostanoid overflow into the hepatic vein, but with different quantities and kinetics. Only the C5a-induced but not the zymosan-induced effects were abrogated by inhibitors of prostanoid signaling as the prostanoid synthesis inhibitor indomethacin and the thromboxane receptor antagonist daltroban. In contrast to C5a and zymosan, LPS had no effect on glucose output, flow rate, or prostanoid overflow. In isolated Kupffer cells, C5a and zymosan induced maximal release of prostaglandins D(2) and E(2) and of thromboxane A(2) within a period of 0 to 2 minutes and 5 to 15 minutes, respectively. In pulse-chase experiments, maximal prostanoid release was already observed after 2 minutes of continuous stimulation with C5a, but only after 10 to 15 minutes of continuous stimulation with zymosan. LPS-dependent prostanoid release was not seen before 1 hour. Thus, even though C5a, zymosan, and LPS induced prostanoid release from Kupffer cells, only C5a quickly regulated hepatic glucose metabolism in a prostanoid-dependent manner (due to the kinetics and quantities of prostanoids released).

  8. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia

    OpenAIRE

    Rieg, Timo; Masuda, Takahiro; Gerasimova, Maria; Mayoux, Eric; Platt, Kenneth; Powell, David R.; Thomson, Scott C.; Koepsell, Hermann; Vallon, Volker

    2013-01-01

    In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40–50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the ...

  9. Molecular dynamics simulation studies of GLUT4: substrate-free and substrate-induced dynamics and ATP-mediated glucose transport inhibition.

    Directory of Open Access Journals (Sweden)

    Suma Mohan

    Full Text Available BACKGROUND: Glucose transporter 4 (GLUT4 is an insulin facilitated glucose transporter that plays an important role in maintaining blood glucose homeostasis. GLUT4 is sequestered into intracellular vesicles in unstimulated cells and translocated to the plasma membrane by various stimuli. Understanding the structural details of GLUT4 will provide insights into the mechanism of glucose transport and its regulation. To date, a crystal structure for GLUT4 is not available. However, earlier work from our laboratory proposed a well validated homology model for GLUT4 based on the experimental data available on GLUT1 and the crystal structure data obtained from the glycerol 3-phosphate transporter. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, the dynamic behavior of GLUT4 in a membrane environment was analyzed using three forms of GLUT4 (apo, substrate and ATP-substrate bound states. Apo form simulation analysis revealed an extracellular open conformation of GLUT4 in the membrane favoring easy exofacial binding of substrate. Simulation studies with the substrate bound form proposed a stable state of GLUT4 with glucose, which can be a substrate-occluded state of the transporter. Principal component analysis suggested a clockwise movement for the domains in the apo form, whereas ATP substrate-bound form induced an anti-clockwise rotation. Simulation studies suggested distinct conformational changes for the GLUT4 domains in the ATP substrate-bound form and favor a constricted behavior for the transport channel. Various inter-domain hydrogen bonds and switching of a salt-bridge network from E345-R350-E409 to E345-R169-E409 contributed to this ATP-mediated channel constriction favoring substrate occlusion and prevention of its release into cytoplasm. These data are consistent with the biochemical studies, suggesting an inhibitory role for ATP in GLUT-mediated glucose transport. CONCLUSIONS/SIGNIFICANCE: In the absence of a crystal structure for any

  10. A novel chalcone derivative attenuates the diabetes-induced renal injury via inhibition of high glucose-mediated inflammatory response and macrophage infiltration

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Qilu [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zhao, Leping [Department of Pharmacy, the Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wang, Yi; Zhang, Yali [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Zhaoyu [Department of International High School, Shanghai Jiaotong University Nanyang Affiliated (Kunshan) School, Minhang District, Shanghai (China); Pan, Yong; Kanchana, Karvannan; Wang, Jingying; Tong, Chao [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Dan, E-mail: yqyyld@163.com [Department of Nephrology, the Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2015-01-15

    Inflammation plays a central role in the development and progression of diabetic nephropathy (DN). Researches on novel anti-inflammatory agents may offer new opportunities for the treatment of DN. We previously found a chalcone derivative L6H21 could inhibit LPS-induced cytokine release from macrophages. The aim of this study was to investigate whether L6H21 could ameliorate the high glucose-mediated inflammation in NRK-52E cells and attenuate the inflammation-mediated renal injury. According to the results, L6H21 showed a great inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines, and macrophage adhesion via down-regulation of NF-κB/MAPKs activity in high glucose-stimulated renal NRK-52E cells. Further, in vivo oral administration with L6H21 at a dosage of 20 mg/kg/2 days showed a decreased expression of pro-inflammatory cytokines, cell adhesion molecules, which subsequently contributed to the inhibition on renal macrophage infiltration, the reduction of serum creatinine and BUN levels, and the improvement on the fibrosis and pathological changes in the renal tissues of diabetic mice. These findings provided that chalcone derived L6H21 may be a promising anti-inflammatory agent and have the potential in the therapy of diabetic nephropathy, and importantly, MAPK/NF-κB signaling system may be a novel therapeutic target for human DN in the future. - Highlights: • Inflammation plays a central role in the development of diabetic nephropathy. • Compound L6H21 reduced the high glucose-mediated inflammation in NRK-52E cells. • Compound L6H21 attenuated the inflammation-mediated renal injury. • L6H21 exhibited anti-inflammatory effects via inactivation of NF-κB/MAPKs. • MAPKs/NF-κB may be a novel therapeutic target in diabetic nephropathy treatment.

  11. Glucose elevates NITRATE TRANSPORTER2.1 protein levels and nitrate transport activity independently of its HEXOKINASE1-mediated stimulation of NITRATE TRANSPORTER2.1 expression.

    Science.gov (United States)

    de Jong, Femke; Thodey, Kate; Lejay, Laurence V; Bevan, Michael W

    2014-01-01

    Mineral nutrient uptake and assimilation is closely coordinated with the production of photosynthate to supply nutrients for growth. In Arabidopsis (Arabidopsis thaliana), nitrate uptake from the soil is mediated by genes encoding high- and low-affinity transporters that are transcriptionally regulated by both nitrate and photosynthate availability. In this study, we have studied the interactions of nitrate and glucose (Glc) on gene expression, nitrate transport, and growth using glucose-insensitive2-1 (gin2-1), which is defective in sugar responses. We confirm and extend previous work by showing that HEXOKINASE1-mediated oxidative pentose phosphate pathway (OPPP) metabolism is required for Glc-mediated NITRATE TRANSPORTER2.1 (NRT2.1) expression. Treatment with pyruvate and shikimate, two products derived from intermediates of the OPPP that are destined for amino acid production, restores wild-type levels of NRT2.1 expression, suggesting that metabolites derived from OPPP metabolism can, together with Glc, directly stimulate high levels of NRT2.1 expression. Nitrate-mediated NRT2.1 expression is not influenced by gin2-1, showing that Glc does not influence NRT2.1 expression through nitrate-mediated mechanisms. We also show that Glc stimulates NRT2.1 protein levels and transport activity independently of its HEXOKINASE1-mediated stimulation of NRT2.1 expression, demonstrating another possible posttranscriptional mechanism influencing nitrate uptake. In gin2-1 plants, nitrate-responsive biomass growth was strongly reduced, showing that the supply of OPPP metabolites is essential for assimilating nitrate for growth.

  12. Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells

    Science.gov (United States)

    Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S.; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A.; Ghosh, Partha Pratim; Mitra, Prasenjit

    2016-06-01

    Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation.

  13. The flavanone homoeriodictyol increases SGLT-1-mediated glucose uptake but decreases serotonin release in differentiated Caco-2 cells

    Science.gov (United States)

    Hoi, Julia Katharina; Holik, Ann-Katrin; Geissler, Katrin; Hans, Joachim; Friedl, Barbara; Liszt, Kathrin; Krammer, Gerhard E.; Ley, Jakob P.; Somoza, Veronika

    2017-01-01

    Flavanoids and related polyphenols, among them hesperitin, have been shown to modulate cellular glucose transport by targeting SGLT-1 and GLUT-2 transport proteins. We aimed to investigate whether homoeriodictyol, which is structurally related to hesperitin, affects glucose uptake in differentiated Caco-2 cells as a model for the intestinal barrier. The results revealed that, in contrast to other polyphenols, the flavanon homoeriodictyol promotes glucose uptake by 29.0 ± 3.83% at a concentration of 100 μM. The glucose uptake stimulating effect was sensitive to phloridzin, but not to phloretin, indicating an involvement of the sodium-coupled glucose transporter SGLT-1, but not of sodium-independent glucose transporters (GLUT). In addition, in contrast to the increased extracellular serotonin levels by stimulation with 500 mM D-(+)-glucose, treatment with 100 μM homoeriodictyol decreased serotonin release by –48.8 ± 7.57% in Caco-2 cells via a phloridzin-sensitive signaling pathway. Extracellular serotonin levels were also reduced by –57.1 ± 5.43% after application of 0.01 μM homoeriodictyol to human neural SH-SY5Y cells. In conclusion, we demonstrate that homoeriodictyol affects both the glucose metabolism and the serotonin system in Caco-2 cells via a SGLT-1-meditated pathway. Furthermore, the results presented here support the usage of Caco-2 cells as a model for peripheral serotonin release. Further investigations may address the value of homoeriodictyol in the treatment of anorexia and malnutrition through the targeting of SGLT-1. PMID:28192456

  14. Label-free assay for the detection of glucose mediated by the effects of narrowband absorption on quantum dot photoluminescence

    Science.gov (United States)

    Khan, Saara A.; Smith, Gennifer T.; Ellerbee, Audrey K.

    2014-03-01

    We present a novel strategy for label-free detection of glucose based on CdSe/ZnS core/shell quantum dots (QDs). We exploit the concentration-dependent, narrowband absorption of the hexokinase-glucose 6-phosphate dehydrogenase enzymatic assay to selectively filter a 365-nm excitation source, leading to a proportional decrease in the photoluminescence intensity of the QDs. The visible wavelength emission of the QDs enables quantitative readout using standard visible detectors (e.g., CCD). Experimental results show highly linear QD photoluminescence over the clinically relevant glucose concentration range of 1-25mM, in excellent agreement with detection methods demonstrated by others. The method has a demonstrated limit of detection of 3.5μM, also on par with the best proposed methods. A significant advantage of our strategy is the complete elimination of QDs as a consumable. In contrast with other methods of QD-based measurement of glucose, our system does not require the glucose solution to be mixed with the QDs, thereby decreasing its overall cost and making it an ideal strategy for point-of-care detection of glucose in low-resource areas. Furthermore, readout can be accomplished with low-cost, portable detectors such as cellular phones, eliminating the need for expensive and bulky spectrophotometers to output quantitative information. The general strategy we present is useful for other biosensing applications involving chemistries with unique absorption peaks falling within the excitation band of available QDs.

  15. Long-term Aβ exposure augments mCa2+-independent mROS-mediated depletion of cardiolipin for the shift of a lethal transient mitochondrial permeability transition to its permanent mode in NARP cybrids: a protective targeting of melatonin.

    Science.gov (United States)

    Hsiao, Chia-Wei; Peng, Tsung-I; Peng, Alexander C; Reiter, Russel J; Tanaka, Masashi; Lai, Yiu-Kay; Jou, Mei-Jie

    2013-01-01

    Mitochondrial dysfunction is a hallmark of amyloid β-peptide (Aβ)-induced neurodegeneration of Alzheimer's disease (AD). This study investigated whether mtDNA T8993G mutation-induced complex V inhibition, clinically associated with neurological muscle weakness, ataxia, and retinitis pigmentosa (NARP), is a potential risk factor for AD and the pathological link for long-term exposure of Aβ-induced mitochondrial toxicity and apoptosis in NARP cybrids. Using noninvasive fluorescence probe-coupled laser scanning imaging microscopy and NARP cybrids harboring 98% mutant genes along with its parental 143B osteosarcoma cells, we demonstrated that Aβ-augmented mitochondrial Ca(2+) (mCa(2+))-independent mitochondrial reactive oxygen species (mROS) formation for a cardiolipin (CL, a major mitochondrial protective phospholipid)-dependent lethal modulation of the mitochondrial permeability transition (MPT). Aβ augmented not only the amount but also the propagation rate of mROS-induced mROS formation to significantly depolarize mitochondrial membrane potential (∆Ψ(m)) and reduce mCa(2+) stress. Aβ-augmented mROS oxidized and depleted CL, thereby enhances mitochondrial fission and movement retardation, which promoted the NARP-augmented lethal transient-MPT (t-MPT) to switch to its irreversible mode of permanent-MPT (p-MPT). Interestingly, melatonin, a multiple mitochondrial protector, markedly reduced Aβ-augmented mROS formation and therefore significantly reduced mROS-mediated depolarization of ∆Ψ(m), fission of mitochondria and retardation of mitochondrial movement to stabilize CL and hence the MPT. In the presence of melatonin, Aβ-promoted p-MPT was reversed to a protective t-MPT, which preserved ∆Ψ(m) and lowered elevated mCa(2+) to sublethal levels for an enhanced mCa(2+)-dependent O(2) consumption. Thus, melatonin may potentially rescue AD patients associated with NARP symptoms.

  16. Inhibition of glucose-and fructose-mediated protein glycation by infusions and ethanolic extracts of ten culinary herbs and spices

    Institute of Scientific and Technical Information of China (English)

    Jugjeet Singh Ramkissoon; Mohamad Fawzi Mahomoodally; Anwar Hussein Subratty; Nessar Ahmed

    2016-01-01

    Objective: To investigate the inhibitory activity of ten culinary herbs and spices namely on glucose-mediated glycation(GMG) and fructose-mediated glycation(FMG) of bovine serum albumin.Methods: Fluorescence was used as an index of albumin glycation using glucose and fructose as substrates in the presence of infusions and ethanolic extracts of ten culinary herbs and spices. Antioxidant activity of the extracts was evaluated using reducing power,metal ion chelating and superoxide radical scavenging assays. Phytochemicals profile was analysed using 13 standard methods.Results: FMG was found to be significantly higher than GMG(95 and 84 AU,respectively; P 0.05) was found in the percentage glycation inhibitory activity of infusions compared to ethanolic extracts. The mean percentage inhibitory activity of the extracts for GMG(45.9%) and for FMG(45.1%) was not significantly different(P > 0.05). Qualitative phytochemical analysis showed the presence of alkaloids, flavonoids, tannins, terpenoids, anthraquinones, steroids, reducing sugars, proteins, phenols,saponins, phlobatannins, and cardiac glycosides.Conclusions: The higher rate of fluorescence generation by fructation suggests that glycation by fructose deserves much attention as a glycating agent. Data herein showed that the extracts inhibited GMG and FMG. Thus, these edible plants could be a natural source of antioxidants and anti-glycation agent for preventing advanced glycation endproducts-mediated complications.

  17. Charge mediation by ruthenium poly(pyridine) complexes in 'second-generation' glucose biosensors based on carboxymethylated beta-cyclodextrin polymer membranes.

    Science.gov (United States)

    Kosela, Edyta; Elzanowska, Hanna; Kutner, Wlodzimierz

    2002-04-01

    Four different poly(pyridine) complexes of ruthenium, viz. Ru(II)(trpy)(phen)(OH(2))](2+) (1), trans-[Ru(III)(2,2'bpy)(2)(OH(2))(OH)](2+) (2), [(2,2'bpy)(2)(OH)Ru(III)ORu(III)(OH)(2,2'bpy)(2)](4+) (3), and [Ru(II)(4,4'bpy)(NH(3))(5)](2+) (4) (2,2'bpy=2,2'-bipyridine, 4,4'bpy=4,4'-bipyridine, trpy=2,2',2"-terpyridine, phen=1,10-phenanthroline), were tested as non-physiological charge mediators of 'second-generation' glucose biosensors. The membranes for these biosensors were prepared by casting anionic carboxymethylated beta-cyclodextrin polymer films (beta-CDPA) directly onto the Pt or glassy carbon (GC) disk electrodes. Simultaneously, glucose oxidase (GOD) was immobilized in the films by covalent bonding and the Ru complexes were incorporated both by inclusion in the beta-CD molecular cavities and by ion exchange at the fixed carboxymethyl cation-exchange sites. The leakage of the mediator from the polymer has been minimized by adopting a suitable pre-treatment procedure. The biosensors catalytic activities increased in the order 1inclusion complex with beta-CD, the biosensor sensitivity was the highest and equal to 7.2 micro A mM(-1) cm(-2), detectability was as low as 1 mM, but the linear concentration range was limited only to 4 mM. In contrast, for complexes 2 and 3 the sensitivity was 0.4 and 3.2 micro A mM(-1) cm(-2), while the linear concentration range extended up to at least 24 and 14 mM glucose, respectively. Even though some common interfering substances, such as ascorbate, paracetamol or urea, are oxidized at potentials close to those of the Ru complex redox couples, their electro-oxidation currents at physiological concentrations are insignificant compared to those due to the biocatalytic oxidation of glucose. The biosensor response to glucose is reversible as demonstrated by the inhibition of GOD activity by Cu(II). That is, the Cu(II) concentration required to inhibit by half the response to glucose of the biosensor containing complex 2 was 1.0 m

  18. Mild Glucose Starvation Induces KDM2A-Mediated H3K36me2 Demethylation through AMPK To Reduce rRNA Transcription and Cell Proliferation.

    Science.gov (United States)

    Tanaka, Yuji; Yano, Hirohisa; Ogasawara, Sachiko; Yoshioka, Sho-Ichi; Imamura, Hiromi; Okamoto, Kengo; Tsuneoka, Makoto

    2015-12-01

    Environmental conditions control rRNA transcription. Previously, we found that serum and glucose deprivation induces KDM2A-mediated H3K36me2 demethylation in the rRNA gene (rDNA) promoter and reduces rRNA transcription in the human breast cancer cell line MCF-7. However, the molecular mechanism and biological significance are still unclear. In the present study, we found that glucose starvation alone induced the KDM2A-dependent reduction of rRNA transcription. The treatment of cells with 2-deoxy-d-glucose, an inhibitor of glycolysis, reduced rRNA transcription and H3K36me2 in the rDNA promoter, both of which were completely dependent on KDM2A in low concentrations of 2-deoxy-d-glucose, that is, mild starvation conditions. The mild starvation induced these KDM2A activities through AMP-activated kinase (AMPK) but did not affect another AMPK effector of rRNA transcription, TIF-IA. In the triple-negative breast cancer cell line MDA-MB-231, the mild starvation also reduced rRNA transcription in a KDM2A-dependent manner. We detected KDM2A in breast cancer tissues irrespective of their estrogen receptor, progesterone receptor, and HER2 status, including triple-negative cancer tissues. In both MCF-7 and MDA-MB-231 cells, mild starvation reduced cell proliferation, and KDM2A knockdown suppressed the reduction of cell proliferation. These results suggest that under mild glucose starvation AMPK induces KDM2A-dependent reduction of rRNA transcription to control cell proliferation.

  19. iNOS-derived peroxynitrite mediates high glucose-induced inflammatory gene expression in vascular smooth muscle cells through promoting KLF5 expression and nitration.

    Science.gov (United States)

    Zhang, Man-Li; Zheng, Bin; Tong, Fei; Yang, Zhan; Wang, Zhi-Bo; Yang, Bao-Ming; Sun, Yan; Zhang, Xin-Hua; Zhao, Yi-Lin; Wen, Jin-Kun

    2017-07-12

    Inducible NO synthase (iNOS) expression and peroxynitrite formation are significantly increased in diabetic vascular tissues. Transcription factor KLF5 activates iNOS gene transcription and is involved in vascular inflammatory injury and remodeling. However, mutual regulation between KLF5, iNOS and peroxynitrite in diabetic vascular inflammation, as well as the underlying mechanisms, remain largely unknown. In this study, we found a marked increase in KLF5 and iNOS expression in vascular smooth muscle cells (VSMC) of diabetic patients. High glucose-induced expression of KLF5 and iNOS was also observed in cultured mouse VSMCs. Further investigation showed that high glucose induced KLF5 nitration by iNOS-mediated peroxynitrite generation, and nitrated KLF5 increased its interaction with NF-κB p50 and thus cooperatively activated the expression of inflammatory cytokines TNF-α and IL-1β. Furthermore, we showed that the VSMC-specific knockout of KLF5 dramatically reduced inflammatory cytokine expression in the vascular tissues of diabetic mice. Moreover, 17β-estradiol (E2) inhibited high glucose-mediated effects in VSMCs, and in the response to E2, estrogen receptor (ER) α competed with KLF5 for binding to NF-κB p50, which in turn leads to the suppression of inflammatory gene expression in VSMCs. Together, the present findings were the first to show that KLF5 expression and nitration by iNOS-mediated peroxynitrite are necessary for the induction of TNF-α and IL-1β expression in VSMCs of diabetic vascular tissues. Copyright © 2017. Published by Elsevier B.V.

  20. Dibenzoylmethane exerts metabolic activity through regulation of AMP-activated protein kinase (AMPK-mediated glucose uptake and adipogenesis pathways.

    Directory of Open Access Journals (Sweden)

    Nami Kim

    Full Text Available Dibenzoylmethane (DBM has been shown to exert a variety of beneficial effects on human health. However, the mechanism of action is poorly understood. In this study, DBM increased phosphorylation of AMP-activated protein kinase (AMPK and stimulated glucose uptake in a skeletal muscle cell line. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor blocked DBM-induced glucose uptake. DBM increased the concentration of intracellular calcium and glucose uptake due to DBM was abolished by STO-609 (a calcium/calmodulin-dependent protein kinase inhibitor. DBM stimulated phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK, which was blocked by pretreatment with compound C, an AMPK inhibitor. The expression of glucose transporter type 4 (GLUT4 was increased by DBM. The translocation of GLUT4 to the plasma membrane was also increased by DBM in AMPK dependently. In addition, DBM suppressed weight gain and prevented fat accumulation in the liver and abdomen in mice fed a high-fat diet. In pre-adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC, the rate-limiting enzyme of fatty acid synthesis. Expression of the adipogenic gene, fatty acid synthase (FAS, was suppressed by DBM in an AMPK-dependent manner. These results showed that the beneficial metabolic effects of DBM might be due to regulation of glucose uptake via AMPK in skeletal muscle and inhibition of adipogenesis in pre-adipocytes.

  1. Sulfide as an alternative electron donor to glucose for power generation in mediator-less microbial fuel cell.

    Science.gov (United States)

    Fatemi, Sakine; Ghoreyshi, Ali A; Rahimnejad, Mostafa; Darzi, Ghasem Najafpour; Pant, Deepak

    2017-07-31

    The objective of this study was to investigate the power generation in a dual-chamber microbial fuel cell (MFC). As one of the effective parameters, glucose concentration was studied in the range of 100-1000 mg/L. At the optimum concentration of 500 mg/L of glucose, maximum power generation was 186 mW/m(2). As an alternative, sulfide was used as an electron donor and maximum power output was 401 mW/m(2) at the concentration of 100 mg/L; which was more than twice of power produced using glucose. Moreover, sulfide removal efficiencies of 70%, 66%, 60%, and 64% were obtained when initial sulfide concentrations of 10, 20, 80, and 100 mg/L were used, respectively.

  2. The loss of glucose-regulated protein 78 (GRP78) during normal aging or from siRNA knockdown augments human alpha-synuclein (α-syn) toxicity to rat nigral neurons.

    Science.gov (United States)

    Salganik, Maxim; Sergeyev, Valeriy G; Shinde, Vishal; Meyers, Craig A; Gorbatyuk, Marina S; Lin, Jonathan H; Zolotukhin, Sergey; Gorbatyuk, Oleg S

    2015-06-01

    Age-related structural changes and gradual loss of key enzymes significantly affect the ability of the endoplasmic reticulum (ER) to facilitate proper protein folding and maintain homeostasis. In this work, we present several lines of evidence supporting the hypothesis that the age-related decline in expression of the ER chaperone glucose-regulated protein 78 (GRP78) could be related to the development of Parkinson's disease. We first determined that old (24 months) rats exhibit significantly lower levels of GRP78 protein in the nigrostriatal system as compared with young (2 months) animals. Then using recombinant adeno-associate virus-mediated gene transfer, we found that GRP78 downregulation by specific small interfering RNAs (siRNAs) aggravates alpha-synuclein (α-syn) neurotoxicity in nigral dopamine (DA) neurons. Moreover, the degree of chaperone decline corresponds with the severity of neurodegeneration. Additionally, comparative analysis of nigral tissues obtained from old and young rats revealed that aging affects the capacity of nigral DA cells to upregulate endogenous GRP78 protein in response to human α-syn neurotoxicity. Finally, we demonstrated that a sustained increase of GRP78 protein over the course of 9 months protected aging nigral DA neurons in the α-syn-induced rat model of Parkinson's-like neurodegeneration. Our data indicate that the ER chaperone GRP78 may have therapeutic potential for preventing and/or slowing age-related neurodegeneration.

  3. Oxygen-glucose deprivation preconditioning protects neurons against oxygen-glucose deprivation/reperfusion induced injury via bone morphogenetic protein-7 mediated ERK, p38 and Smad signalling pathways.

    Science.gov (United States)

    Guan, Junhong; Du, Shaonan; Lv, Tao; Qu, Shengtao; Fu, Qiang; Yuan, Ye

    2016-01-01

    Bone morphogenetic protein (BMP)-7 mediated neuroprotective effect of cerebral ischemic preconditioning (IPC) has been studied in an ischemic animal model, but the underlying cellular mechanisms have not been clearly clarified. In this study, primary cortical neurons and the SH-SY5Y cell line were used to investigate the role of BMP-7 and its downstream signals in the neuroprotective effects of oxygen-glucose deprivation preconditioning (OGDPC). Immunocytochemistry was used to detect the expression of neurofilament in neurons. MTT and lactate dehydrogenase activity assays were used to measure the cytotoxicity. Western blot was used to detect the protein expression of BMP-7 and downstream signals. BMP inhibitor, mitogen-activated protein kinase inhibitors, Smad inhibitor and siRNA of Smad 1 were used to investigate the role of corresponding signalling pathways in the OGDPC. Results showed that OGDPC-induced overexpression of BMP-7 in primary cortical neurons and SH-SY5Y cells. Both of endogenous and exogenous BMP-7 could replicate the neuroprotective effects seen in OGDPC pretreatment. In addition, extracellular regulated protein kinases, p38 and Smad signalling pathway were found to be involved in the neuroprotective effects mediated by OGDPC via BMP-7. This study primarily reveals the cellular mechanisms of the neuroprotection mediated by OGDPC, and provides evidence for better understanding of this intrinsic factor against ischemia.

  4. ARLearn: augmented reality meets augmented virtuality

    NARCIS (Netherlands)

    Ternier, Stefaan; Klemke, Roland; Kalz, Marco; Van Ulzen, Patricia; Specht, Marcus

    2012-01-01

    Ternier, S., Klemke, R., Kalz, M., Van Ulzen, P., & Specht, M. (2012). ARLearn: augmented reality meets augmented virtuality [Special issue]. Journal of Universal Computer Science - Technology for learning across physical and virtual spaces, 18(15), 2143-2164.

  5. ARLearn: augmented reality meets augmented virtuality

    NARCIS (Netherlands)

    Ternier, Stefaan; Klemke, Roland; Kalz, Marco; Van Ulzen, Patricia; Specht, Marcus

    2012-01-01

    Ternier, S., Klemke, R., Kalz, M., Van Ulzen, P., & Specht, M. (2012). ARLearn: augmented reality meets augmented virtuality [Special issue]. Journal of Universal Computer Science - Technology for learning across physical and virtual spaces, 18(15), 2143-2164.

  6. Augmentative phalloplasty.

    Science.gov (United States)

    Panfilov, Dimitrije E

    2006-01-01

    Until 20 years ago, penis size (either nonerected or erected) was not mentioned, discussed, or defined even in serious books of human anatomy. The need of some men to enlarge and elongate their penile size is equivalent to the need of some women to ask for breast augmentation. The same method of transferring autologous fat into other parts of the body can be used in male patients for augmentative phalloplasty. The circumference of the penis increases 2 to 3 cm, and before of a heavier penis, the length increases 1 to 2 cm. If more lengthening is desired, subtotal dissection of the ligament fundiforme penis below the symphysis could be done, pull the corpus cavernosus out, and fix the tunica albuginea at the periost. At the root of the phallus, the skin can be elongated by V-Y-plasty, and the scrotal skin can be released by 1 or 2 Z-plasties. Combining both autologous fat transfer and ligament release allows for penis elongation of 3 to 5 cm. The authors have performed augentative phalloplasty on 88 patients since 1996. They have transplanted 40 to 68 ml of pure fat. Of the 88 patients, 57 underwent autologous fat transfer only, and 31 received additional ligament release. Penis length increased 1.5 to 4.8 cm (average, 2.42 cm), and circumference increased 1.4 to 4.0 cm (average, 2.65 cm). The initial penis lengths were 6.5 to 10.0 cm (average, 8.72 cm), and the circumference were 8.0 to 10.1 cm (average, 9.18 cm) not erected. This article details a simple operative procedure to enlarge the penis and simple postoperative bandages. Patients are advised to obstain from sexual activity for 5 weeks after the surgery. Two patients who disregarded this advice had an unsatisfactory result. In one patient too, much of the grafted fat had to be removed from the preputium. No other serious complications were observed.

  7. Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes.

    Science.gov (United States)

    Ngo, Sherry; Barry, Janelle B; Nisbet, Janelle C; Prins, Johannes B; Whitehead, Jonathan P

    2009-04-10

    Excess glucocorticoids induce insulin resistance and reduce glucose uptake although the underlying mechanisms are unclear. Here we demonstrate that Dex (1 microM for 24h) inhibits basal and insulin (1 nM) stimulated glucose uptake in human and murine adipocytes by 50% with a concomitant reduction in the levels of GLUT1/4 at the plasma membrane but no change in total GLUT1/4 levels. Expression and phosphorylation of proximal insulin signalling molecules (IRS1, PI3K, AKT) was unaffected by Dex as was phosphorylation of mTOR and FOXO1. In contrast, phosphorylation of AKT substrate 160kDa (AS160) at T642, which is essential for 14-3-3 recruitment and GLUT4 translocation, was reduced by 50% in basal and insulin-stimulated cells and this was mirrored by decreased 14-3-3 association. Co-treatment with the glucocorticoid receptor antagonist RU486 (10 microM) abrogated the Dex effect on AS160-T642 phosphorylation and restored glucose uptake by 80%. These data suggest Dex inhibits glucose uptake in adipocytes, at least in part, by reducing AS160 phosphorylation and interaction with 14-3-3.

  8. Isoflavone genistein protects high glucose-induced human aortic endothelial cell apoptosis through estrogen receptor-mediated pathway

    Institute of Scientific and Technical Information of China (English)

    Wenwen Zhong; Yang Liu; Guang Yang; Hui Tian

    2008-01-01

    Objective The aim of this study was to determine if isoflavone genistien has protective effects against high glucose-induced cell apoptosis in human aortic endlthelial cells,and investigate the possible mechanism for this protection.Methods Human aortic endothelial cells subjected to normal (5mmol/L) or high glucose (25mmol/L) were treated with genistein at 0,50,100nmol/L.Parallel experiments were performed with 100nM 17b-estradiol,and also in the presence and absence of the pure anti-estrogen ICI-182,780 (100nmol/L).The effects on cell apoptotic DNA fragmentation were determined using cell death ELISA,and the effects on cellular proliferation were determined using tritiated thymidine incorporation assay.Estrogen receptor expression was detected by Taqman quantitative PCR.Results Genistein at 100nmol/L significantly reduced high glucose-induced DNA fragmentation,and reversed cell DNA synthesis inhibition (P<0.001) after 24 hours' incubation.The effect of genistein was completely blocked by ICI-182,780administration.Estrogen receptor beta,but not alpha was found to be expressed in these cells.Conclusion Isoflavone genistein shows protection against high glucose-induced cell damage through estrogen receptor beta,reducing apoptotic DNA damage and protecting from the inhibition of cell proliferation.

  9. Period2 gene mutant mice show compromised insulin-mediated endothelial nitric oxide release and altered glucose homeostasis

    Directory of Open Access Journals (Sweden)

    João Miguel Carvas

    2012-08-01

    Full Text Available Period2 (Per2 is an important component of the circadian clock. Mutation of this gene is associated with vascular endothelial dysfunction and altered glucose metabolism. The aim of this study is to further characterize whole body glucose homeostasis and endothelial NO production in response to insulin in the mPer2Brdm1 mice. We show that mPer2Brdm1 mice exhibit compromised insulin receptor activation and Akt signaling in various tissues including liver, fat, heart, and aortas with a tissue-specific heterogeneous diurnal pattern, and decreased insulin-stimulated endothelial NO release in the aortas in both active and inactive phases of the animals. As compared to wild type mice, the mPer2Brdm1 mice reveal hyperinsulinemia, hypoglycemia with lower fasting hepatic glycogen content and glycogen synthase level, no difference in glucose tolerance and insulin tolerance. The mPer2Brdm1 mice do not show increased predisposition to obesity either on normal chow or high fat diet compared to wild type controls. Thus, mice with Per2 gene mutation show altered glucose homeostasis and compromised insulin-stimulated endothelial NO release, independently of obesity.

  10. A glucose transporter can mediate ribose uptake: definition of residues that confer substrate specificity in a sugar transporter.

    Science.gov (United States)

    Naula, Christina M; Logan, Flora J; Logan, Flora M; Wong, Pui Ee; Barrett, Michael P; Burchmore, Richard J

    2010-09-24

    Sugars, the major energy source for many organisms, must be transported across biological membranes. Glucose is the most abundant sugar in human plasma and in many other biological systems and has been the primary focus of sugar transporter studies in eukaryotes. We have previously cloned and characterized a family of glucose transporter genes from the protozoan parasite Leishmania. These transporters, called LmGT1, LmGT2, and LmGT3, are homologous to the well characterized glucose transporter (GLUT) family of mammalian glucose transporters. We have demonstrated that LmGT proteins are important for parasite viability. Here we show that one of these transporters, LmGT2, is a more effective carrier of the pentose sugar d-ribose than LmGT3, which has a 6-fold lower relative specificity (V(max)/K(m)) for ribose. A pair of threonine residues, located in the putative extracellular loops joining transmembrane helices 3 to 4 and 7 to 8, define a filter that limits ribose approaching the exofacial substrate binding pocket in LmGT3. When these threonines are substituted by alanine residues, as found in LmGT2, the LmGT3 permease acquires ribose permease activity that is similar to that of LmGT2. The location of these residues in hydrophilic loops supports recent suggestions that substrate recognition is separated from substrate binding and translocation in this important group of transporters.

  11. Fenton reaction-mediated fluorescence quenching of N-acetyl-L-cysteine-protected gold nanoclusters: analytical applications of hydrogen peroxide, glucose, and catalase detection.

    Science.gov (United States)

    Deng, Hao-Hua; Wu, Gang-Wei; He, Dong; Peng, Hua-Ping; Liu, Ai-Lin; Xia, Xing-Hua; Chen, Wei

    2015-11-21

    Given the importance of hydrogen peroxide (H2O2) in many biological processes and its wide application in various industries, the demand for sensitive, accurate, and economical H2O2 sensors is high. In this study, we used Fenton reaction-stimulated fluorescence quenching of N-acetyl-L-cysteine-protected gold nanoclusters (NAC-AuNCs) as a reporter system for the determination of H2O2. After the experimental conditions were optimized, the sensing platform enabled the analysis of H2O2 with a limit of detection (LOD) as low as 0.027 μM. As the glucose oxidase cascade leads to the generation of H2O2 and catalase catalyzes the decomposition of H2O2, these two biocatalytic procedures can be probed by the Fenton reaction-mediated quenching of NAC-AuNCs. The LOD for glucose was found to be 0.18 μM, and the linear range was 0.39-27.22 μM. The LOD for catalase was 0.002 U mL(-1), and the linear range was 0.01-0.3 U mL(-1). Moreover, the proposed sensing methods were successfully applied for human serum glucose detection and the non-invasive determination of catalase activity in human saliva, demonstrating their great potential for practical applications.

  12. Augmented Reality at the Tactical and Operational Levels of War

    Science.gov (United States)

    2015-10-24

    FINAL 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Augmented Reality at the Tactical and Operational Levels of War... Augmented reality technologies have reached a stage where commercially viable systems will soon enter the consumer market. These technologies merge...direct tactical forces. 15. SUBJECT TERMS Augmented Reality , Mediated Reality , Smartphone, HUD, HMD, Information Technology 16. SECURITY

  13. Methyl 6-Amino-6-deoxy-d-pyranoside-Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism.

    Science.gov (United States)

    Li, Taoli; Gao, Xiangqian; Yang, Liu; Shi, Yunli; Gao, Qingzhi

    2016-05-19

    Methyl 6-aminodeoxy-d-pyranoside-derived platinum(II) glycoconjugates were designed and synthesized based on the clinical drug oxaliplatin for glucose transporter (GLUT)-mediated tumor targeting. In addition to a substantial improvement in water solubility, the conjugates exhibited cytotoxicity similar to or higher than that of oxaliplatin in six different human cancer cell lines. GLUT-mediated transport of the complexes was investigated with a cell-based fluorescence competition assay and GLUT-inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing human colorectal adenocarcinoma (HT29) cell line. The antitumor effect of the aminodeoxypyranoside-conjugated platinum(II) complexes was found to depend significantly on the GLUT inhibitor, and the cellular uptake of the molecules was regulated by GLUT-mediated transport. The results from this study demonstrate the potential advantages of aminodeoxypyranosides as sugar motifs for glycoconjugation for Warburg-effect-targeted drug design. These fundamental results also support the potential of aminodeoxypyranoside-conjugated platinum(II) complexes as lead compounds for further preclinical evaluation.

  14. l-Cysteine supplementation increases insulin sensitivity mediated by upregulation of GSH and adiponectin in high glucose treated 3T3-L1 adipocytes.

    Science.gov (United States)

    Achari, Arunkumar E; Jain, Sushil K

    2017-09-15

    Diabetic patients have lower blood levels of l-cysteine (LC) and glutathione (GSH). This study examined the hypothesis that LC supplementation positively up regulates the effects of insulin on GSH and glucose metabolism in 3T3-L1 adipocyte model. 3T3L1 adipocytes were treated with LC (250 μM, 2 h) and/or insulin (15 or 30 nM, 2 h), and high glucose (HG, 25 mM, 20 h). Results showed that HG caused significant increase (95%) in ROS and reduction in the protein levels of DsbA-L (43%), adiponectin (64%), GCLC (20%), GCLM (21%), GSH (50%), and GLUT-4 (23%) in adipocytes. Furthermore, HG caused a reduction in total (35%) and HMW adiponectin (30%) secretion. Treatment with insulin alone significantly (p L, adiponectin, GCLC, GCLM, GSH, and GLUT-4 protein levels, glucose utilization, and improved total and HMW adiponectin secretion in HG treated adipocytes compared to HG alone. Interestingly, LC supplementation along with insulin caused greater reduction in ROS levels and significantly (p L (41% vs LC, 29% vs Insulin), adiponectin (92% Vs LC, 84% Vs insulin) protein levels and total (32% Vs LC, 22% Vs insulin) and HMW adiponectin (75% Vs LC, 39% Vs insulin) secretion compared with the either insulin or LC alone in HG-treated cells. In addition, LC supplementation along with insulin increased GCLC (21% Vs LC, 14% insulin), GCLM (28% Vs LC, 16% insulin) and GSH (25% Vs LC and insulin) levels compared with the either insulin or LC alone in HG-treated cells. Furthermore, LC and insulin increases GLUT-4 protein expression (65% Vs LC, 18% Vs Insulin), glucose utilization (57% Vs LC, 27% Vs insulin) compared with the either insulin or LC alone in HG-treated cells. Similarly, LC supplementation increased insulin action significantly in cells maintained in medium contained control glucose. To explore the beneficial effect of LC is mediated by the upregulation of GCLC, we knocked down GCLC using siRNA in adipoctyes. There was a significant decrease in DsbA-L and GLUT-4 m

  15. A glucose biofuel cell implanted in rats.

    Directory of Open Access Journals (Sweden)

    Philippe Cinquin

    Full Text Available Powering future generations of implanted medical devices will require cumbersome transcutaneous energy transfer or harvesting energy from the human body. No functional solution that harvests power from the body is currently available, despite attempts to use the Seebeck thermoelectric effect, vibrations or body movements. Glucose fuel cells appear more promising, since they produce electrical energy from glucose and dioxygen, two substrates present in physiological fluids. The most powerful ones, Glucose BioFuel Cells (GBFCs, are based on enzymes electrically wired by redox mediators. However, GBFCs cannot be implanted in animals, mainly because the enzymes they rely on either require low pH or are inhibited by chloride or urate anions, present in the Extra Cellular Fluid (ECF. Here we present the first functional implantable GBFC, working in the retroperitoneal space of freely moving rats. The breakthrough relies on the design of a new family of GBFCs, characterized by an innovative and simple mechanical confinement of various enzymes and redox mediators: enzymes are no longer covalently bound to the surface of the electron collectors, which enables use of a wide variety of enzymes and redox mediators, augments the quantity of active enzymes, and simplifies GBFC construction. Our most efficient GBFC was based on composite graphite discs containing glucose oxidase and ubiquinone at the anode, polyphenol oxidase (PPO and quinone at the cathode. PPO reduces dioxygen into water, at pH 7 and in the presence of chloride ions and urates at physiological concentrations. This GBFC, with electrodes of 0.133 mL, produced a peak specific power of 24.4 microW mL(-1, which is better than pacemakers' requirements and paves the way for the development of a new generation of implantable artificial organs, covering a wide range of medical applications.

  16. A glucose biofuel cell implanted in rats.

    Science.gov (United States)

    Cinquin, Philippe; Gondran, Chantal; Giroud, Fabien; Mazabrard, Simon; Pellissier, Aymeric; Boucher, François; Alcaraz, Jean-Pierre; Gorgy, Karine; Lenouvel, François; Mathé, Stéphane; Porcu, Paolo; Cosnier, Serge

    2010-05-04

    Powering future generations of implanted medical devices will require cumbersome transcutaneous energy transfer or harvesting energy from the human body. No functional solution that harvests power from the body is currently available, despite attempts to use the Seebeck thermoelectric effect, vibrations or body movements. Glucose fuel cells appear more promising, since they produce electrical energy from glucose and dioxygen, two substrates present in physiological fluids. The most powerful ones, Glucose BioFuel Cells (GBFCs), are based on enzymes electrically wired by redox mediators. However, GBFCs cannot be implanted in animals, mainly because the enzymes they rely on either require low pH or are inhibited by chloride or urate anions, present in the Extra Cellular Fluid (ECF). Here we present the first functional implantable GBFC, working in the retroperitoneal space of freely moving rats. The breakthrough relies on the design of a new family of GBFCs, characterized by an innovative and simple mechanical confinement of various enzymes and redox mediators: enzymes are no longer covalently bound to the surface of the electron collectors, which enables use of a wide variety of enzymes and redox mediators, augments the quantity of active enzymes, and simplifies GBFC construction. Our most efficient GBFC was based on composite graphite discs containing glucose oxidase and ubiquinone at the anode, polyphenol oxidase (PPO) and quinone at the cathode. PPO reduces dioxygen into water, at pH 7 and in the presence of chloride ions and urates at physiological concentrations. This GBFC, with electrodes of 0.133 mL, produced a peak specific power of 24.4 microW mL(-1), which is better than pacemakers' requirements and paves the way for the development of a new generation of implantable artificial organs, covering a wide range of medical applications.

  17. Aspirin-mediated acetylation of haemoglobin increases in presence of high glucose concentration and decreases protein glycation

    OpenAIRE

    Francesco Finamore; Feliciano Priego-Capote; Severine Nolli; Pierre Fontana; Jean-Charles Sanchez

    2015-01-01

    Glycation represents the first stage in the development of diabetic complications. Aspirin was shown to prevent sugars reacting with proteins, but the exact mechanism of this interaction was not well defined. We performed a quantitative analysis to calculate the levels of acetylation and glycation of haemoglobin, among others red blood cell (RBC) proteins, using a label free approach. After glucose incubation, increases in the acetylation levels were seen for several haemoglobin subunits, whi...

  18. The Mitochondrial 2-Oxoglutarate Carrier Is Part of a Metabolic Pathway That Mediates Glucose- and Glutamine-stimulated Insulin Secretion*

    OpenAIRE

    Odegaard, Matthew L.; Joseph, Jamie W.; Jensen, Mette V.; Lu, Danhong; Ilkayeva, Olga; Ronnebaum, Sarah M.; Becker, Thomas C.; Newgard, Christopher B.

    2010-01-01

    Glucose-stimulated insulin secretion from pancreatic islet β-cells is dependent in part on pyruvate cycling through the pyruvate/isocitrate pathway, which generates cytosolic α-ketoglutarate, also known as 2-oxoglutarate (2OG). Here, we have investigated if mitochondrial transport of 2OG through the 2-oxoglutarate carrier (OGC) participates in control of nutrient-stimulated insulin secretion. Suppression of OGC in clonal pancreatic β-cells (832/13 cells) and isolated rat islets by adenovirus-...

  19. High Glucose-Mediated STAT3 Activation in Endometrial Cancer Is Inhibited by Metformin: Therapeutic Implications for Endometrial Cancer

    Science.gov (United States)

    Wallbillich, John J.; Josyula, Srirama; Saini, Uksha; Zingarelli, Roman A.; Dorayappan, Kalpana Deepa Priya; Riley, Maria K.; Wanner, Ross A.; Cohn, David E.; Selvendiran, Karuppaiyah

    2017-01-01

    Objectives STAT3 is over-expressed in endometrial cancer, and diabetes is a risk factor for the development of type 1 endometrial cancer. We therefore investigated whether glucose concentrations influence STAT3 expression in type 1 endometrial cancer, and whether such STAT3 expression might be inhibited by metformin. Methods In Ishikawa (grade 1) endometrial cancer cells subjected to media with low, normal, or high concentrations of glucose, expression of STAT3 and its target proteins was evaluated by real-time quantitative PCR (qPCR). Ishikawa cells were treated with metformin and assessed with cell proliferation, survival, migration, and ubiquitin assays, as well as Western blot and qPCR. Expression of apoptosis proteins was evaluated with Western blot in Ishikawa cells transfected with a STAT3 overexpression plasmid and treated with metformin. A xenograft tumor model was used for studying the in vivo efficacy of metformin. Results Expression of STAT3 and its target proteins was increased in Ishikawa cells cultured in high glucose media. In vitro, metformin inhibited cell proliferation, survival and migration but induced apoptosis. Metformin reduced expression levels of pSTAT3 ser727, total STAT3, and its associated cell survival and anti-apoptotic proteins. Additionally, metformin treatment was associated with increased degradation of pSTAT3 ser727. No change in apoptotic protein expression was noticed with STAT3 overexpression in Ishikawa cells. In vivo, metformin treatment led to a decrease in tumor weight as well as reductions of STAT3, pSTAT3 ser727, its target proteins. Conclusions These results suggest that STAT3 expression in type 1 endometrial cancer is stimulated by a high glucose environment and inhibited by metformin. PMID:28114390

  20. Particulate Air Pollution and Fasting Blood Glucose in Nondiabetic Individuals: Associations and Epigenetic Mediation in the Normative Aging Study, 2000–2011

    Science.gov (United States)

    Peng, Cheng; Bind, Marie-Abele C.; Colicino, Elena; Kloog, Itai; Byun, Hyang-Min; Cantone, Laura; Trevisi, Letizia; Zhong, Jia; Brennan, Kasey; Dereix, Alexandra E.; Vokonas, Pantel S.; Coull, Brent A.; Schwartz, Joel D.; Baccarelli, Andrea A.

    2016-01-01

    Background: Among nondiabetic individuals, higher fasting blood glucose (FBG) independently predicts diabetes risk, cardiovascular disease, and dementia. Ambient PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 μm) is an emerging determinant of glucose dysregulation. PM2.5 effects and mechanisms are understudied among nondiabetic individuals. Objectives: Our goals were to investigate whether PM2.5 is associated with an increase in FBG and to explore potential mediating roles of epigenetic gene regulation. Methods: In 551 nondiabetic participants in the Normative Aging Study, we measured FBG, and DNA methylation of four inflammatory genes (IFN-γ, IL-6, ICAM-1, and TLR-2), up to four times between 2000 and 2011 (median = 2). We estimated short- and medium-term (1-, 7-, and 28-day preceding each clinical visit) ambient PM2.5 at each participant’s address using a validated hybrid land-use regression satellite-based model. We fitted covariate-adjusted regression models accounting for repeated measures. Results: Mean FBG was 99.8 mg/dL (SD = 10.7), 18% of the participants had impaired fasting glucose (IFG; i.e., 100–125 mg/dL FBG) at first visit. Interquartile increases in 1-, 7-, and 28-day PM2.5 were associated with 0.57 mg/dL (95% CI: 0.02, 1.11, p = 0.04), 1.02 mg/dL (95% CI: 0.41, 1.63, p = 0.001), and 0.89 mg/dL (95% CI: 0.32, 1.47, p = 0.003) higher FBG, respectively. The same PM2.5 metrics were associated with 13% (95% CI: –3%, 33%, p = 0.12), 27% (95% CI: 6%, 52%, p = 0.01) and 32% (95% CI: 10%, 58%, p = 0.003) higher odds of IFG, respectively. PM2.5 was negatively correlated with ICAM-1 methylation (p = 0.01), but not with other genes. Mediation analysis estimated that ICAM-1 methylation mediated 9% of the association of 28-day PM2.5 with FBG. Conclusions: Among nondiabetics, short- and medium-term PM2.5 were associated with higher FBG. Mediation analysis indicated that part of this association was mediated by ICAM-1 promoter methylation

  1. Unique palindromic sequences in synthetic oligonucleotides are required to induce IFN [correction of INF] and augment IFN-mediated [correction of INF] natural killer activity.

    Science.gov (United States)

    Yamamoto, S; Yamamoto, T; Kataoka, T; Kuramoto, E; Yano, O; Tokunaga, T

    1992-06-15

    Thirty-mer single-stranded oligonucleotides, with a sequence chosen from the known cDNA encoding the 64-kDa protein named Ag A or the MPB-70 protein of Mycobacterium bovis BCG and the human cellular proteins such as complement component 1 inhibitor and Ig rearranged lambda-chain, were used to dissect the capability to induce IFN and to augment NK cell activity of mouse spleen cells by coincubation in vitro. Three with the hexamer palindromic sequence as GACGTC were active, whereas two kinds of oligonucleotides with no palindrome were inactive. The oligonucleotides containing at least one of the different palindromic sequences showed no activity. When a portion of the sequence of the inactive oligonucleotides was substituted with either palindromic sequence of GACGTC, AGCGCT, or AACGTT, the oligonucleotide acquired the ability to augment NK activity. In contrast, the oligonucleotides substituted with another palindromic sequence such as ACCGGT was without effect. Furthermore, exchange of two neighboring mononucleotides within, but not outside, the active palindromic sequence destroyed the ability of the oligonucleotides to augment NK cell activity. Stimulation of spleen cells with the substituted oligonucleotide, A4a-AAC, induced production of significant amounts of IFN-alpha/beta and small amounts of IFN-gamma. Augmentation of NK activity of the cells by the oligonucleotide was ascribed to IFN-alpha/beta production. These results strongly suggest that the presence of the unique palindromic sequences, such as GACGTC, AGCGCT, and AACGTT, but not ACCGGT, is essential for the immunostimulatory activity of oligonucleotides.

  2. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Gang [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Hosomi, Naohisa [Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa (Japan); Lei, Bai; Nakano, Daisuke [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu [Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Ma, Hong [Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Griendling, Kathy K. [Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (United States); Nishiyama, Akira [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan)

    2011-10-15

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  3. Formation of Core-Shell Particles by Interfacial Radical Polymerization Initiated by a Glucose Oxidase-Mediated Redox System.

    Science.gov (United States)

    Shenoy, Raveesh; Tibbitt, Mark W; Anseth, Kristi S; Bowman, Christopher N

    2013-03-12

    A unique design paradigm to form core-shell particles based on interfacial radical polymerization is described. The interfacial initiation system is comprised of an enzymatic reaction between glucose and glucose oxidase (GOx) to generate hydrogen peroxide, which, in the presence of iron (Fe(2+)), generates hydroxyl radicals that initiate polymerization. Shell formation on prefabricated polymeric cores is achieved by localizing the initiation reaction to the interface of the core and a surrounding aqueous monomer formulation into which it is immersed. The interfacially confined initiation reaction is accomplished by incorporating one or more of the initiating species in the particle core and the remainder of the complementary initiating components in the surrounding media such that interactions and the resulting initiation reaction occur at the interface. This work is focused on engineering the reaction behavior and mass transport processes to promote interfacially confined polymerization, controlling the rate of shell formation, and manipulating the structure of the core-shell particle. Specifically, incorporating GOx in the precursor solution used to fabricate cores ranging from 100 to 200 μm, and the remainder of the complementary initiating components and monomer in the bulk solution prior to interfacial polymerization yielded shells whose average thickness was 20 μm after 4 min of immersion and at a bulk iron concentration of 12.5 mM. When the locations of glucose and GOx are interchanged, the average thickness of the shell was 15 or 100 μm for bulk iron concentrations of 45 and 12.5 mM, respectively. The initial locations of glucose and GOx also determine the degree of interpenetration of the core and the shell. Specifically, for a bulk iron concentration of 45 mM, the thickness of the interpenetrating layer averaged 12 μm when GOx was initially within the core, whereas no interpenetrating layer was observed when glucose was incorporated in the core. The

  4. Effects of CaMKII-mediated phosphorylation of ryanodine receptor type 2 on islet calcium handling, insulin secretion, and glucose tolerance.

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    Sayali S Dixit

    Full Text Available Altered insulin secretion contributes to the pathogenesis of type 2 diabetes. This alteration is correlated with altered intracellular Ca(2+-handling in pancreatic β cells. Insulin secretion is triggered by elevation in cytoplasmic Ca(2+ concentration ([Ca(2+]cyt of β cells. This elevation in [Ca(2+]cyt leads to activation of Ca(2+/calmodulin-dependent protein kinase II (CAMKII, which, in turn, controls multiple aspects of insulin secretion. CaMKII is known to phosphorylate ryanodine receptor 2 (RyR2, an intracellular Ca(2+-release channel implicated in Ca(2+-dependent steps of insulin secretion. Our data show that RyR2 is CaMKII phosphorylated in a pancreatic β-cell line in a glucose-sensitive manner. However, it is not clear whether any change in CaMKII-mediated phosphorylation underlies abnormal RyR2 function in β cells and whether such a change contributes to alterations in insulin secretion. Therefore, knock-in mice with a mutation in RyR2 that mimics its constitutive CaMKII phosphorylation, RyR2-S2814D, were studied. This mutation led to a gain-of-function defect in RyR2 indicated by increased basal RyR2-mediated Ca(2+ leak in islets of these mice. This chronic in vivo defect in RyR2 resulted in basal hyperinsulinemia. In addition, S2814D mice also developed glucose intolerance, impaired glucose-stimulated insulin secretion and lowered [Ca(2+]cyt transients, which are hallmarks of pre-diabetes. The glucose-sensitive Ca(2+ pool in islets from S2814D mice was also reduced. These observations were supported by immunohistochemical analyses of islets in diabetic human and mouse pancreata that revealed significantly enhanced CaMKII phosphorylation of RyR2 in type 2 diabetes. Together, these studies implicate that the chronic gain-of-function defect in RyR2 due to CaMKII hyperphosphorylation is a novel mechanism that contributes to pathogenesis of type 2 diabetes.

  5. Effects of CaMKII-Mediated Phosphorylation of Ryanodine Receptor Type 2 on Islet Calcium Handling, Insulin Secretion, and Glucose Tolerance

    Science.gov (United States)

    Dixit, Sayali S.; Wang, Tiannan; Manzano, Eiffel John Q.; Yoo, Shin; Lee, Jeongkyung; Chiang, David Y.; Ryan, Nicole; Respress, Jonathan L.; Yechoor, Vijay K.; Wehrens, Xander H. T.

    2013-01-01

    Altered insulin secretion contributes to the pathogenesis of type 2 diabetes. This alteration is correlated with altered intracellular Ca2+-handling in pancreatic β cells. Insulin secretion is triggered by elevation in cytoplasmic Ca2+ concentration ([Ca2+]cyt) of β cells. This elevation in [Ca2+]cyt leads to activation of Ca2+/calmodulin-dependent protein kinase II (CAMKII), which, in turn, controls multiple aspects of insulin secretion. CaMKII is known to phosphorylate ryanodine receptor 2 (RyR2), an intracellular Ca2+-release channel implicated in Ca2+-dependent steps of insulin secretion. Our data show that RyR2 is CaMKII phosphorylated in a pancreatic β-cell line in a glucose-sensitive manner. However, it is not clear whether any change in CaMKII-mediated phosphorylation underlies abnormal RyR2 function in β cells and whether such a change contributes to alterations in insulin secretion. Therefore, knock-in mice with a mutation in RyR2 that mimics its constitutive CaMKII phosphorylation, RyR2-S2814D, were studied. This mutation led to a gain-of-function defect in RyR2 indicated by increased basal RyR2-mediated Ca2+ leak in islets of these mice. This chronic in vivo defect in RyR2 resulted in basal hyperinsulinemia. In addition, S2814D mice also developed glucose intolerance, impaired glucose-stimulated insulin secretion and lowered [Ca2+]cyt transients, which are hallmarks of pre-diabetes. The glucose-sensitive Ca2+ pool in islets from S2814D mice was also reduced. These observations were supported by immunohistochemical analyses of islets in diabetic human and mouse pancreata that revealed significantly enhanced CaMKII phosphorylation of RyR2 in type 2 diabetes. Together, these studies implicate that the chronic gain-of-function defect in RyR2 due to CaMKII hyperphosphorylation is a novel mechanism that contributes to pathogenesis of type 2 diabetes. PMID:23516528

  6. AtRH57, a DEAD-box RNA helicase, is involved in feedback inhibition of glucose-mediated abscisic acid accumulation during seedling development and additively affects pre-ribosomal RNA processing with high glucose.

    Science.gov (United States)

    Hsu, Yi-Feng; Chen, Yun-Chu; Hsiao, Yu-Chun; Wang, Bing-Jyun; Lin, Shih-Yun; Cheng, Wan-Hsing; Jauh, Guang-Yuh; Harada, John J; Wang, Co-Shine

    2014-01-01

    The Arabidopsis thaliana T-DNA insertion mutant rh57-1 exhibited hypersensitivity to glucose (Glc) and abscisic acid (ABA). The other two rh57 mutants also showed Glc hypersensitivity similar to rh57-1, strongly suggesting that the Glc-hypersensitive feature of these mutants results from mutation of AtRH57. rh57-1 and rh57-3 displayed severely impaired seedling growth when grown in Glc concentrations higher than 3%. The gene, AtRH57 (At3g09720), was expressed in all Arabidopsis organs and its transcript was significantly induced by ABA, high Glc and salt. The new AtRH57 belongs to class II DEAD-box RNA helicase gene family. Transient expression of AtRH57-EGFP (enhanced green fluorescent protein) in onion cells indicated that AtRH57 was localized in the nucleus and nucleolus. Purified AtRH57-His protein was shown to unwind double-stranded RNA independent of ATP in vitro. The ABA biosynthesis inhibitor fluridone profoundly redeemed seedling growth arrest mediated by sugar. rh57-1 showed increased ABA levels when exposed to high Glc. Quantitative real time polymerase chain reaction analysis showed that AtRH57 acts in a signaling network downstream of HXK1. A feedback inhibition of ABA accumulation mediated by AtRH57 exists within the sugar-mediated ABA signaling. AtRH57 mutation and high Glc conditions additively caused a severe defect in small ribosomal subunit formation. The accumulation of abnormal pre-rRNA and resistance to protein synthesis-related antibiotics were observed in rh57 mutants and in the wild-type Col-0 under high Glc conditions. These results suggested that AtRH57 plays an important role in rRNA biogenesis in Arabidopsis and participates in response to sugar involving Glc- and ABA signaling during germination and seedling growth.

  7. GDM-Induced Macrosomia Is Reversed by Cav-1 via AMPK-Mediated Fatty Acid Transport and GLUT1-Mediated Glucose Transport in Placenta

    Science.gov (United States)

    Wang, Di; Yang, Ruirui; Sang, Hui; Han, Linlin; Zhu, Yuexia; Lu, Yanyan; Tan, Yeke; Shang, Zhanping

    2017-01-01

    Objective To investigate if the role of Cav-1 in GDM-induced macrosomia is through regulating AMPK signaling pathway in placenta. Methods We used diagnostic criteria of gestational diabetes mellitus (GDM) and macrosomia to separate and compare placental protein and mRNA levels from GDM with macrosomia group (GDMM), GDM with normal birth weight group (GDMN) and normal glucose tolerance (NGT) with normal birth weight group (CON). Western blotting was performed to examine differentially expressed proteins of caveolin-1 (Cav-1) and Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway related proteins, including phosphorylated-AMPKα(Thr172), AMPKα, phosphorylated-Acetyl-CoA carboxylase(Ser79) (p-ACC(Ser79)), ACC and glucose transporter 1 (GLUT1) in placenta between the three groups. The mRNA levels of Cav-1, AMPKα, ACC and GLUT1 in placenta were measured by real time-PCR. Results In the GDMM placenta group, both protein and mRNA levels of Cav-1 were down-regulated, while GLUT1 was up-regulated; the phosphorylation and mRNA levels of ACC and AMPKα were decreased, but total ACC protein levels were increased compared to both the GDMN (pGLUT1 protein levels. Besides, in GDMM group placental mRNA levels, NBW had a positive correlation with GLUT1 (pGLUT1 (pGLUT1. Conclusion GDM-induced macrosomias have more severe inhibition of Cav-1 expression in placenta. Cav-1 is associated with placental glucose and fatty acid transport via the induction of AMPK signaling pathway and the reduction of GLUT1 signaling pathway to reverse GDM-induced macrosomia. PMID:28125642

  8. Luminal Glucose Does Not Enhance Active Intestinal Calcium Absorption in mice: Evidence Against a Role for Cav1.3 as a Mediator of Calcium Uptake During Absorption

    Science.gov (United States)

    Reyes-Fernandez, Perla C.; Fleet, James C.

    2015-01-01

    Intestinal Ca absorption occurs through a 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)-regulated transcellular pathway, especially when habitual dietary Ca intake is low. Recently the L-type voltage-gated Ca channel, Cav1.3, was proposed to mediate active, transcellular Ca absorption in response to membrane depolarization caused by elevated luminal glucose levels following a meal. We tested the hypothesis that high luminal glucose could reveal a role for Cav1.3 in active intestinal Ca absorption in mice. Nine week-old male C57BL/6J mice were fed AIN93G diets containing either low (0.125%) or high (1%) Ca for 1 week and Ca absorption was examined by an oral gavage method using a 45Ca-transport buffer containing 25 mmol/L of glucose or fructose. Transient receptor potential vanilloid 6 (TRPV6), Calbindin D9k (CaBPD9k) and Cav1.3 mRNA levels were measured in the duodenum, jejunum and ileum. TRPV6 and CaBPD9k expression were highest in the duodenum, where active, 1,25(OH)2D3-regulated Ca absorption occurs while Cav1.3 mRNA levels were similar across the intestinal segments. As expected, the low Ca diet increased renal cytochrome p450-27B1 (CYP27B1) mRNA (p=0.003), serum 1,25(OH)2D3 (p<0.001) and Ca absorption efficiency by 2-fold with the fructose buffer. However, the glucose buffer used to favor Cav1.3 activation did not increase Ca absorption efficiency (p=0.6) regardless of the dietary Ca intake level. Collectively, our results show that glucose did not enhance Ca absorption and they do not support a critical role for Cav1.3 in either basal or vitamin D-regulated intestinal Ca absorption in vivo. PMID:26403486

  9. Aspirin-mediated acetylation of haemoglobin increases in presence of high glucose concentration and decreases protein glycation

    Directory of Open Access Journals (Sweden)

    Francesco Finamore

    2015-09-01

    Full Text Available Glycation represents the first stage in the development of diabetic complications. Aspirin was shown to prevent sugars reacting with proteins, but the exact mechanism of this interaction was not well defined. We performed a quantitative analysis to calculate the levels of acetylation and glycation of haemoglobin, among others red blood cell (RBC proteins, using a label free approach. After glucose incubation, increases in the acetylation levels were seen for several haemoglobin subunits, while a parallel decrease of their glycation levels was observed after aspirin incubation. These results suggest that, a mutual influence between these two modifications, occur at protein level.

  10. Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK

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    Sung-Jun Park

    2017-04-01

    Full Text Available The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK, an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief, the metabolic effects produced by SRT1720 require AMPK, which can be activated independently of Sirt1.

  11. Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK.

    Science.gov (United States)

    Park, Sung-Jun; Ahmad, Faiyaz; Um, Jee-Hyun; Brown, Alexandra L; Xu, Xihui; Kang, Hyeog; Ke, Hengming; Feng, Xuesong; Ryall, James; Philp, Andrew; Schenk, Simon; Kim, Myung K; Sartorelli, Vittorio; Chung, Jay H

    2017-04-01

    The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK), an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE) in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief, the metabolic effects produced by SRT1720 require AMPK, which can be activated independently of Sirt1. Published by Elsevier B.V.

  12. Deletion of Rab GAP AS160 modifies glucose uptake and GLUT4 translocation in primary skeletal muscles and adipocytes and impairs glucose homeostasis

    Science.gov (United States)

    Lansey, Melissa N.; Walker, Natalie N.; Hargett, Stefan R.; Stevens, Joseph R.

    2012-01-01

    Tight control of glucose uptake in skeletal muscles and adipocytes is crucial to glucose homeostasis and is mediated by regulating glucose transporter GLUT4 subcellular distribution. In cultured cells, Rab GAP AS160 controls GLUT4 intracellular retention and release to the cell surface and consequently regulates glucose uptake into cells. To determine AS160 function in GLUT4 trafficking in primary skeletal muscles and adipocytes and investigate its role in glucose homeostasis, we characterized AS160 knockout (AS160−/−) mice. We observed increased and normal basal glucose uptake in isolated AS160−/− adipocytes and soleus, respectively, while insulin-stimulated glucose uptake was impaired and GLUT4 expression decreased in both. No such abnormalities were found in isolated AS160−/− extensor digitorum longus muscles. In plasma membranes isolated from AS160−/− adipose tissue and gastrocnemius/quadriceps, relative GLUT4 levels were increased under basal conditions and remained the same after insulin treatment. Concomitantly, relative levels of cell surface-exposed GLUT4, determined with a glucose transporter photoaffinity label, were increased in AS160−/− adipocytes and normal in AS160−/− soleus under basal conditions. Insulin augmented cell surface-exposed GLUT4 in both. These observations suggest that AS160 is essential for GLUT4 intracellular retention and regulation of glucose uptake in adipocytes and skeletal muscles in which it is normally expressed. In vivo studies revealed impaired insulin tolerance in the presence of normal (male) and impaired (female) glucose tolerance. Concurrently, insulin-elicited increases in glucose disposal were abolished in all AS160−/− skeletal muscles and liver but not in AS160−/− adipose tissues. This suggests AS160 as a target for differential manipulation of glucose homeostasis. PMID:23011063

  13. Deletion of Rab GAP AS160 modifies glucose uptake and GLUT4 translocation in primary skeletal muscles and adipocytes and impairs glucose homeostasis.

    Science.gov (United States)

    Lansey, Melissa N; Walker, Natalie N; Hargett, Stefan R; Stevens, Joseph R; Keller, Susanna R

    2012-11-15

    Tight control of glucose uptake in skeletal muscles and adipocytes is crucial to glucose homeostasis and is mediated by regulating glucose transporter GLUT4 subcellular distribution. In cultured cells, Rab GAP AS160 controls GLUT4 intracellular retention and release to the cell surface and consequently regulates glucose uptake into cells. To determine AS160 function in GLUT4 trafficking in primary skeletal muscles and adipocytes and investigate its role in glucose homeostasis, we characterized AS160 knockout (AS160(-/-)) mice. We observed increased and normal basal glucose uptake in isolated AS160(-/-) adipocytes and soleus, respectively, while insulin-stimulated glucose uptake was impaired and GLUT4 expression decreased in both. No such abnormalities were found in isolated AS160(-/-) extensor digitorum longus muscles. In plasma membranes isolated from AS160(-/-) adipose tissue and gastrocnemius/quadriceps, relative GLUT4 levels were increased under basal conditions and remained the same after insulin treatment. Concomitantly, relative levels of cell surface-exposed GLUT4, determined with a glucose transporter photoaffinity label, were increased in AS160(-/-) adipocytes and normal in AS160(-/-) soleus under basal conditions. Insulin augmented cell surface-exposed GLUT4 in both. These observations suggest that AS160 is essential for GLUT4 intracellular retention and regulation of glucose uptake in adipocytes and skeletal muscles in which it is normally expressed. In vivo studies revealed impaired insulin tolerance in the presence of normal (male) and impaired (female) glucose tolerance. Concurrently, insulin-elicited increases in glucose disposal were abolished in all AS160(-/-) skeletal muscles and liver but not in AS160(-/-) adipose tissues. This suggests AS160 as a target for differential manipulation of glucose homeostasis.

  14. GDM-Induced Macrosomia Is Reversed by Cav-1 via AMPK-Mediated Fatty Acid Transport and GLUT1-Mediated Glucose Transport in Placenta.

    Science.gov (United States)

    Yao, Guo; Zhang, Yafang; Wang, Di; Yang, Ruirui; Sang, Hui; Han, Linlin; Zhu, Yuexia; Lu, Yanyan; Tan, Yeke; Shang, Zhanping

    2017-01-01

    To investigate if the role of Cav-1 in GDM-induced macrosomia is through regulating AMPK signaling pathway in placenta. We used diagnostic criteria of gestational diabetes mellitus (GDM) and macrosomia to separate and compare placental protein and mRNA levels from GDM with macrosomia group (GDMM), GDM with normal birth weight group (GDMN) and normal glucose tolerance (NGT) with normal birth weight group (CON). Western blotting was performed to examine differentially expressed proteins of caveolin-1 (Cav-1) and Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway related proteins, including phosphorylated-AMPKα(Thr172), AMPKα, phosphorylated-Acetyl-CoA carboxylase(Ser79) (p-ACC(Ser79)), ACC and glucose transporter 1 (GLUT1) in placenta between the three groups. The mRNA levels of Cav-1, AMPKα, ACC and GLUT1 in placenta were measured by real time-PCR. In the GDMM placenta group, both protein and mRNA levels of Cav-1 were down-regulated, while GLUT1 was up-regulated; the phosphorylation and mRNA levels of ACC and AMPKα were decreased, but total ACC protein levels were increased compared to both the GDMN (p<0.05) and CON groups (p<0.05). In GDMM placenta group, there was a significant negative correlation observed between neonatal birth weight (NBW) and protein expression levels of Cav-1, p-ACC(Ser79) and p-AMPKα(Thr172) (p<0.05), while positive relationship with ACC and GLUT1 protein levels. Besides, in GDMM group placental mRNA levels, NBW had a positive correlation with GLUT1 (p<0.05), while negative with Cav-1, AMPKα and ACC expression (p<0.05). Cav-1 protein expression was positively associated with p-AMPK and p-ACC (p<0.05), and negatively associated with GLUT1 (p<0.05). Interestingly, p-AMPK protein expression was closely related to p-ACC (p<0.05), but not with GLUT1. GDM-induced macrosomias have more severe inhibition of Cav-1 expression in placenta. Cav-1 is associated with placental glucose and fatty acid transport via the induction

  15. Inhibition of glucose- and fructose-mediated protein glycation by infusions and ethanolic extracts of ten culinary herbs and spices

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    Jugjeet Singh Ramkissoon

    2016-06-01

    Conclusions: The higher rate of fluorescence generation by fructation suggests that glycation by fructose deserves much attention as a glycating agent. Data herein showed that the extracts inhibited GMG and FMG. Thus, these edible plants could be a natural source of antioxidants and anti-glycation agent for preventing advanced glycation end-products-mediated complications.

  16. Insulin-mediated suppression of lipolysis in adipose tissue and skeletal muscle of obese type 2 diabetic men and men with normal glucose tolerance.

    Science.gov (United States)

    Jocken, Johan W E; Goossens, Gijs H; Boon, Hanneke; Mason, Rachael R; Essers, Yvonne; Havekes, Bas; Watt, Matthew J; van Loon, Luc J; Blaak, Ellen E

    2013-10-01

    Impaired regulation of lipolysis and accumulation of lipid intermediates may contribute to obesity-related insulin resistance and type 2 diabetes mellitus. We investigated insulin-mediated suppression of lipolysis in abdominal subcutaneous adipose tissue (AT) and skeletal muscle (SM) of obese men with normal glucose tolerance (NGT) and obese type 2 diabetic men. Eleven NGT men and nine long-term diagnosed type 2 diabetic men (7 ± 1 years), matched for age (58 ± 2 vs 62 ± 2 years), BMI (31.4 ± 0.6 vs 30.5 ± 0.6 kg/m(2)) and [Formula: see text] (28.9 ± 1.5 vs 29.5 ± 2.4 ml kg(-1) min(-1)) participated in this study. Interstitial glycerol concentrations in AT and SM were assessed using microdialysis during a 1 h basal period and a 6 h stepwise hyperinsulinaemic-euglycaemic clamp (8, 20 and 40 mU m(-2) min(-1)). AT and SM biopsies were collected to investigate underlying mechanisms. Hyperinsulinaemia suppressed interstitial SM glycerol concentrations less in men with type 2 diabetes (-7 ± 6%, -13 ± 9% and -27 ± 9%) compared with men with NGT (-21 ± 7%, -38 ± 8% and -53 ± 8%) (p = 0.014). This was accompanied by increased circulating fatty acid and glycerol concentrations, a lower glucose infusion rate (21.8 ± 3.1 vs 30.5 ± 2.0 μmol kg body weight(-1) min(-1); p lipolysis may promote the accumulation of membrane saturated DAG, aggravating insulin resistance, at least partly mediated by PKC. This may represent an important mechanism involved in the progression of insulin resistance towards type 2 diabetes. ClinicalTrials.gov NCT01680133.

  17. Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance.

    Directory of Open Access Journals (Sweden)

    Sophie R Sayers

    Full Text Available Enteroendocrine L-cells synthesise and release the gut hormone glucagon-like peptide-1 (GLP-1 in response to food transit. Deletion of the tumour suppressor kinase LKB1 from proglucagon-expressing cells leads to the generation of intestinal polyps but no change in circulating GLP-1 levels. Here, we explore the role of the downstream kinase AMP-activated protein kinase (AMPK in these cells.Loss of AMPK from proglucagon-expressing cells was achieved using a preproglucagon promoter-driven Cre (iGluCre to catalyse recombination of floxed alleles of AMPKα1 and α2. Oral and intraperitoneal glucose tolerance were measured using standard protocols. L-cell mass was measured by immunocytochemistry. Hormone and peptide levels were measured by electrochemical-based luminescence detection or radioimmunoassay.Recombination with iGluCre led to efficient deletion of AMPK from intestinal L- and pancreatic alpha-cells. In contrast to mice rendered null for LKB1 using the same strategy, mice deleted for AMPK displayed an increase (WT: 0.05 ± 0.01, KO: 0.09±0.02%, p<0.01 in L-cell mass and elevated plasma fasting (WT: 5.62 ± 0.800 pg/ml, KO: 14.5 ± 1.870, p<0.01 and fed (WT: 15.7 ± 1.48pg/ml, KO: 22.0 ± 6.62, p<0.01 GLP-1 levels. Oral, but not intraperitoneal, glucose tolerance was significantly improved by AMPK deletion, whilst insulin and glucagon levels were unchanged despite an increase in alpha to beta cell ratio (WT: 0.23 ± 0.02, KO: 0.33 ± 0.03, p<0.01.AMPK restricts L-cell growth and GLP-1 secretion to suppress glucose tolerance. Targeted inhibition of AMPK in L-cells may thus provide a new therapeutic strategy in some forms of type 2 diabetes.

  18. Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model.

    Science.gov (United States)

    Zhang, Huaqiu; Xie, Minjie; Schools, Gary P; Feustel, Paul F; Wang, Wei; Lei, Ting; Kimelberg, Harold K; Zhou, Min

    2009-01-09

    Pretreatment of ovarectomized rats with estrogen shows long-term protection via activation of the estrogen receptor (ER). However, it remains unknown whether activation of the ER can provide protection against early neuronal damage when given acutely. We simulated ischemic conditions by applying oxygen and glucose deprived (OGD) solution to acute male rat hippocampal slices and examined the neuronal electrophysiological changes. Pyramidal neurons and interneurons showed a time-dependent membrane potential depolarization and reduction in evoked action potential frequency and amplitude over a 10 to 15 min OGD exposure. These changes were largely suppressed by 10 microM TAM. The TAM effect was neuron-specific as the OGD-induced astrocytic membrane potential depolarization was not altered. The TAM effect was mediated through ER activation because it could be simulated by 17beta-estradiol and was completely inhibited by the ER inhibitor ICI 182, 780, and is therefore an example of TAM's selective estrogen receptor modulator (SERM) action. We further show that TAM's effects on OGD-induced impairment of neuronal excitability was largely due to activation of neuroprotective BK channels, as the TAM effect was markedly attenuated by the BK channel inhibitor paxilline at 10 microM. TAM also significantly reduced the frequency and amplitude of AMPA receptor mediated spontaneous excitatory postsynaptic currents (sEPSCs) in pyramidal neurons which is an early consequence of OGD. Altogether, this study demonstrates that both 17beta-estradiol and TAM attenuate neuronal excitability impairment early on in a simulated ischemia model via ER activation mediated potentiation of BK K(+) channels and reduction in enhanced neuronal AMPA/NMDA receptor-mediated excitotoxicity.

  19. Augmented Reality in Astrophysics

    CERN Document Server

    Vogt, Frédéric P A

    2013-01-01

    Augmented Reality consists of merging live images with virtual layers of information. The rapid growth in the popularity of smartphones and tablets over recent years has provided a large base of potential users of Augmented Reality technology, and virtual layers of information can now be attached to a wide variety of physical objects. In this article, we explore the potential of Augmented Reality for astrophysical research with two distinct experiments: (1) Augmented Posters and (2) Augmented Articles. We demonstrate that the emerging technology of Augmented Reality can already be used and implemented without expert knowledge using currently available apps. Our experiments highlight the potential of Augmented Reality to improve the communication of scientific results in the field of astrophysics. We also present feedback gathered from the Australian astrophysics community that reveals evidence of some interest in this technology by astronomers who experimented with Augmented Posters. In addition, we discuss p...

  20. bFGF-Regulating MAPKs Are Involved in High Glucose-Mediated ROS Production and Delay of Vascular Endothelial Cell Migration.

    Directory of Open Access Journals (Sweden)

    Zhong Xin Zhu

    Full Text Available High blood sugar is a symptom of diabetes mellitus (DM. Vascular endothelial cells (VECs directly contact the blood and are damaged when blood sugar levels are high. However, the molecular mechanism underlying this process remains elusive. To analyze the effects of DM on migration, we simulated DM by applying high glucose (HG to the human VEC. HG delayed cell migration and induced phosphorylation of MAPKs (JNK and ERK. By contrast, in presence of bFGF, cell migration was promoted and MAPK phosphorylation levels were reduced. Furthermore, treatment with JNK and ERK inhibitors rescued HG-mediated delay of cell migration. Molecular and cell biological studies demonstrated that HG increased ROS production, whereas treatment with bFGF or JNK/ERK inhibitors blocked HG-induced ROS accumulation. Addition of MnTMPyP, a ROS scavenger, reduced HG-induced ROS production and accelerated cell migration, suggesting that the influence of HG on bFGF-MAPK signaling causes accumulation of ROS, which in turn regulate cell migration. This is the first study to elucidate the molecular mechanism of HG-mediated VEC migration; these findings could facilitate the development of novel therapies for DM.

  1. TLR4 Expression by Liver Resident Cells Mediates the Development of Glucose Intolerance and Insulin Resistance in Experimental Periodontitis.

    Directory of Open Access Journals (Sweden)

    Vladimir Ilievski

    Full Text Available Results from epidemiological studies indicate a close association between periodontitis and type 2 diabetes mellitus. However, the mechanism linking periodontitis to glucose intolerance (GI and insulin resistance (IR is unknown. We therefore tested the hypothesis that periodontitis induces the development of GI/IR through a liver Toll-like receptor 4 (TLR4 dependent mechanism.TLR4 chimeric mice were developed by bone marrow transplantation using green fluorescent protein expressing TLR4WT mouse (GFPWT as donor and TLR4 WT or TLR4-/- as recipient mice (GFPWT:WT and GFPWT:KO chimeras respectively. These chimeras were subjected to experimental chronic periodontitis induced by repeated applications of LPS to the gingival sulci for 18 weeks. The levels of GI/IR were monitored and plasma cytokines and LPS were determined at 18 weeks when differences in glucose tolerance were most apparent. Cytokine gene expression was measured in liver tissue by qPCR.Alveolar bone loss was significantly greater in GFPWT:WT chimeras treated with LPS compared with chimeras treated with PBS or GFPWT:KO chimeras. However, the degree of gingival inflammation was similar between GFPWT:WT and GFPWT:KO mice with LPS application. Severe GI/IR occurred in GFPWT:WT chimeras but not in the GFPWT:KO chimeras that were subjected to 18 weeks of LPS. Serum LPS was detected only in animals to which LPS was applied and the level was similar in GFPWT:WT and GFPWT:KO mice at the 18 week time point. Surprisingly, there was no significant difference in the plasma levels of IL1β, IL6 and TNFα at 18 weeks in spite of the severe GI/IR in the GFPWT:WT chimeras with LPS application. Also, no difference in the expression of TNFα or IL6 mRNA was detected in the liver of GFPWT:WT vs GFPWT:KO mice. In contrast, liver IL1β expression was significantly greater in GFPWT:WT chimeras compared to GFPWT:KO chimeras treated with LPS.We observed that GFPWT:WT, but not GFPWT:KO chimeras, treated with LPS

  2. Daucosterol protects neurons against oxygen-glucose deprivation/reperfusion-mediated injury by activating IGF1 signaling pathway.

    Science.gov (United States)

    Jiang, Li-hua; Yuan, Xiao-lin; Yang, Nian-yun; Ren, Li; Zhao, Feng-ming; Luo, Ban-xin; Bian, Yao-yao; Xu, Jian-ya; Lu, Da-xiang; Zheng, Yuan-yuan; Zhang, Chuan-juan; Diao, Yuan-ming; Xia, Bao-mei; Chen, Gang

    2015-08-01

    We previously reported that daucosterol (a sterolin) up-regulates the expression of insulin-like growth factor I (IGF1)(1) protein in neural stem cells. In this study, we investigated the effects of daucosterol on the survival of cultured cortical neurons after neurons were subjected to oxygen and glucose deprivation and simulated reperfusion (OGD/R)(2), and determined the corresponding molecular mechanism. The results showed that post-treatment of daucosterol significantly reduced neuronal loss, as well as apoptotic rate and caspase-3 activity, displaying the neuroprotective activity. We also found that daucosterol increased the expression level of IGF1 protein, diminished the down-regulation of p-AKT(3) and p-GSK-3β(4), thus activating the AKT(5) signal pathway. Additionally, it diminished the down-regulation of the anti-apoptotic proteins Mcl-1(6) and Bcl-2(7), and decreased the expression level of the pro-apoptotic protein Bax(8), thus raising the ratio of Bcl-2/Bax. The neuroprotective effect of daucosterol was inhibited in the presence of picropodophyllin (PPP)(9), the inhibitor of insulin-like growth factor I receptors (IGF1R)(10). Our study provided information about daucosterol as an efficient and inexpensive neuroprotectants, to which the IGF1-like activity of daucosterol contributes. Daucosterol could be potentially developed as a medicine for ischemic stroke treatment.

  3. Mixed Phytochemicals Mediated Synthesis of Multifunctional Ag-Au-Pd Nanoparticles for Glucose Oxidation and Antimicrobial Applications.

    Science.gov (United States)

    Rao, K Jagajjanani; Paria, Santanu

    2015-07-01

    The growing awareness toward the environment is increasing commercial demand for nanoparticles by green route syntheses. In this study, alloy-like Ag-Au-Pd trimetallic nanoparticles have been prepared by two plants extracts Aegle marmelos leaf (LE) and Syzygium aromaticum bud extracts (CE). Compositionally different Ag-Au-Pd nanoparticles with an atomic ratio of 5.26:2.16:1.0 (by LE) and 11.36:13.14:1.0 (by LE + CE) of Ag:Au:Pd were easily synthesized within 10 min at ambient conditions by changing the composition of phytochemicals. The average diameters of the nanoparticles by LE and LE + CE are ∼8 and ∼11 nm. The catalytic activity of the trimetallic nanoparticles was studied, and they were found to be efficient catalysts for the glucose oxidation process. The prepared nanoparticles also exhibited efficient antibacterial activity against a model Gram-negative bacteria Escherichia coli. The catalytic and antimicrobial properties of these readymade trimetallic nanoparticles have high possibility to be utilized in diverse fields of applications such as health care to environmental.

  4. H-2g, a glucose analog of blood group H antigen, mediates monocyte recruitment in vitro and in vivo via IL-8/CXCL8

    Directory of Open Access Journals (Sweden)

    Rabquer BJ

    2012-09-01

    Full Text Available Bradley J Rabquer,1,2 Yong Hou,1 Jeffrey H Ruth,1 Wei Luo,1 Daniel T Eitzman,1 Alisa E Koch,3,1 Mohammad A Amin11University of Michigan Medical School, Department of Internal Medicine, Ann Arbor, MI, USA; 2Albion College, Biology Department, Albion, MI, USA; 3VA Medical Service, Department of Veterans Affairs, Ann Arbor, MI, USAObjective: Monocyte (MN recruitment is an essential inflammatory component of many autoimmune diseases, including rheumatoid arthritis (RA. In this study we investigated the ability of 2-fucosyllactose (H-2g, a glucose analog of blood group H antigen to induce MN migration in vivo and determined if H-2g-induced interleukin-8 (IL-8/CXCL8 plays a role in MN ingress in RA.Methods: Sponge granuloma and intravital microscopy assays were performed to examine H-2g-induced in vivo MN migration and rolling, respectively. MNs were stimulated with H-2g, and the production of IL-8/CXCL8 was assessed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Lastly, in vitro MN migration assays and an in vivo RA synovial tissue severe combined immunodeficiency mouse model were used to determine the role of IL-8/CXCL8 in H-2g-induced MN migration.Results: In vivo, H-2g induced significantly greater MN migration compared to phosphate buffered saline. Intravital microscopy revealed that H-2g mediates MN migration in vivo by inducing MN rolling. In addition, H-2g induced MN production of IL-8/CXCL8, a process that was dependent on Src kinase. Moreover, we found that H-2g mediated MN migration in vitro, and in vivo migration was inhibited by a neutralizing anti-IL-8/CXCL8 antibody.Conclusion: These findings suggest that H-2g mediates MN recruitment in vitro and in vivo (in part via IL-8/CXCL8.Keywords: inflammation, rheumatoid arthritis, chemokine, migration

  5. Phospho-Rb mediating cell cycle reentry induces early apoptosis following oxygen-glucose deprivation in rat cortical neurons.

    Science.gov (United States)

    Yu, Ying; Ren, Qing-Guo; Zhang, Zhao-Hui; Zhou, Ke; Yu, Zhi-Yuan; Luo, Xiang; Wang, Wei

    2012-03-01

    The aim of this study was to investigate the relationship between cell cycle reentry and apoptosis in cultured cortical neurons following oxygen-glucose deprivation (OGD). We found that the percentage of neurons with BrdU uptake, TUNEL staining, and colocalized BrdU uptake and TUNEL staining was increased relative to control 6, 12 and 24 h after 1 h of OGD. The number of neurons with colocalized BrdU and TUNEL staining was decreased relative to the number of TUNEL-positive neurons at 24 h. The expression of phosphorylated retinoblastoma protein (phospho-Rb) was significantly increased 6, 12 and 24 h after OGD, parallel with the changes in BrdU uptake. Phospho-Rb and TUNEL staining were colocalized in neurons 6 and 12 h after OGD. This colocalization was strikingly decreased 24 h after OGD. Treatment with the cyclin-dependent kinase inhibitor roscovitine (100 μM) decreased the expression of phospho-Rb and reduced neuronal apoptosis in vitro. These results demonstrated that attempted cell cycle reentry with phosphorylation of Rb induce early apoptosis in neurons after OGD and there must be other mechanisms involved in the later stages of neuronal apoptosis besides cell cycle reentry. Phosphoralated Rb may be an important factor which closely associates aberrant cell cycle reentry with the early stages of neuronal apoptosis following ischemia/hypoxia in vitro, and pharmacological interventions for neuroprotection may be useful directed at this keypoint.

  6. Inductively Coupled Augmented Railgun

    CERN Document Server

    Bahder, Thomas B

    2011-01-01

    We derive the non-linear dynamical equations for an augmented electromagnetic railgun, whose augmentation circuit is inductively coupled to the gun circuit. We solve these differential equations numerically using example parameter values. We find a complicated interaction between the augmentation circuit, gun circuit, and mechanical degrees of freedom, leading to a complicated optimization problem. For certain values of parameters, we find that an augmented electromagnetic railgun has an armature kinetic energy that is 42% larger than the same railgun with no augmentation circuit. Optimizing the parameters may lead to further increase in performance.

  7. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  8. Biodegradation behavior and cytotoxicity of the composite membrane composed of beta-dicalcium pyrophosphate and glucose mediated (polyethylene glycol/chitosan).

    Science.gov (United States)

    Wang, Jian Wen; Hon, Min Hsiung

    2004-02-01

    The purpose of this study is to prepare and evaluate the biodegradation behavior and cytotoxicity of a composite membrane, G-beta-DCP, combining beta-dicalcium pyrophosphate (beta-DCP) ceramic particles and glucose mediated chitosan-polyethylene glycol (PEG) membrane. The cytotoxicity of the G-beta-DCP was examined by the in vitro method of NIH 3T3 fibroblast cell culture. Extracts were obtained by soaking the G-beta-DCP composite in lysozyme containing phosphate buffer solution for 2, 7, 14, 21 and 28 days, respectively. The substances released from the G-beta-DCP composite were analyzed by gas chromatography-mass spectrometry (GC-MAS) and inductively coupled plasma atomic emission spectrometry (ICP-AES). The change in morphologies, chemical composition and crystal structure was examined by scanning electron microscopy (SEM) and X-ray diffraction pattern (XRD). The results of extracts cocultured with fibroblasts show that the growth of fibroblasts would increase for the extracts obtained from different beta-DCP feeding weight G-beta-DCP composites after soaking for 7 days. After further increasing the soaking time, the cell number still increases. It is found that the glucose amine and calcium are gradually released from the G-beta-DCP composites, which is considered to be nutritious for the growth of the fibroblast. The release rate of calcium ion and glucosamine concentration can be regulated by feeding the beta-DCP. The degradation behavior of G-beta-DCP composite is considered as an "onion degradation model" that the G-beta-DCP degrades from outer layer to inner layer. The developed material should have a great potential as a cell substrate in the field of tissue engineering.

  9. Honeybee glucose oxidase—its expression in honeybee workers and comparative analyses of its content and H2O2-mediated antibacterial activity in natural honeys

    Science.gov (United States)

    Bucekova, Marcela; Valachova, Ivana; Kohutova, Lenka; Prochazka, Emanuel; Klaudiny, Jaroslav; Majtan, Juraj

    2014-08-01

    Antibacterial properties of honey largely depend on the accumulation of hydrogen peroxide (H2O2), which is generated by glucose oxidase (GOX)-mediated conversion of glucose in diluted honey. However, honeys exhibit considerable variation in their antibacterial activity. Therefore, the aim of the study was to identify the mechanism behind the variation in this activity and in the H2O2 content in honeys associated with the role of GOX in this process. Immunoblots and in situ hybridization analyses demonstrated that gox is solely expressed in the hypopharyngeal glands of worker bees performing various tasks and not in other glands or tissues. Real-time PCR with reference genes selected for worker heads shows that the gox expression progressively increases with ageing of the youngest bees and nurses and reached the highest values in processor bees. Immunoblot analysis of honey samples revealed that GOX is a regular honey component but its content significantly varied among honeys. Neither botanical source nor geographical origin of honeys affected the level of GOX suggesting that some other factors such as honeybee nutrition and/or genetic/epigenetic factors may take part in the observed variation. A strong correlation was found between the content of GOX and the level of generated H2O2 in honeys except honeydew honeys. Total antibacterial activity of most honey samples against Pseudomonas aeruginosa isolate significantly correlated with the H2O2 content. These results demonstrate that the level of GOX can significantly affect the total antibacterial activity of honey. They also support an idea that breeding of novel honeybee lines expressing higher amounts of GOX could help to increase the antibacterial efficacy of the hypopharyngeal gland secretion that could have positive influence on a resistance of colonies against bacterial pathogens.

  10. Honeybee glucose oxidase--its expression in honeybee workers and comparative analyses of its content and H2O2-mediated antibacterial activity in natural honeys.

    Science.gov (United States)

    Bucekova, Marcela; Valachova, Ivana; Kohutova, Lenka; Prochazka, Emanuel; Klaudiny, Jaroslav; Majtan, Juraj

    2014-08-01

    Antibacterial properties of honey largely depend on the accumulation of hydrogen peroxide (H2O2), which is generated by glucose oxidase (GOX)-mediated conversion of glucose in diluted honey. However, honeys exhibit considerable variation in their antibacterial activity. Therefore, the aim of the study was to identify the mechanism behind the variation in this activity and in the H2O2 content in honeys associated with the role of GOX in this process. Immunoblots and in situ hybridization analyses demonstrated that gox is solely expressed in the hypopharyngeal glands of worker bees performing various tasks and not in other glands or tissues. Real-time PCR with reference genes selected for worker heads shows that the gox expression progressively increases with ageing of the youngest bees and nurses and reached the highest values in processor bees. Immunoblot analysis of honey samples revealed that GOX is a regular honey component but its content significantly varied among honeys. Neither botanical source nor geographical origin of honeys affected the level of GOX suggesting that some other factors such as honeybee nutrition and/or genetic/epigenetic factors may take part in the observed variation. A strong correlation was found between the content of GOX and the level of generated H2O2 in honeys except honeydew honeys. Total antibacterial activity of most honey samples against Pseudomonas aeruginosa isolate significantly correlated with the H2O2 content. These results demonstrate that the level of GOX can significantly affect the total antibacterial activity of honey. They also support an idea that breeding of novel honeybee lines expressing higher amounts of GOX could help to increase the antibacterial efficacy of the hypopharyngeal gland secretion that could have positive influence on a resistance of colonies against bacterial pathogens.

  11. Prolonged low flow reduces reactive hyperemia and augments low flow mediated constriction in the brachial artery independent of the menstrual cycle.

    Directory of Open Access Journals (Sweden)

    Mark Rakobowchuk

    Full Text Available Non-invasive forearm ischemia-reperfusion injury and low flow induced vascular dysfunction models provide methods to evaluate vascular function. The role of oestrogen, an endogenous anti-oxidant on recovery from ischemia-reperfusion injury has not been evaluated nor has the impact of prolonged low flow on vascular function been established. Eight healthy women (33±10 yr attended the lab during the follicular, ovulatory and mid-luteal phases of their menstrual cycles. After 30 minutes of rest, brachial artery vascular function was assessed by ultrasound measurements of diameter changes during 5 minutes of forearm ischemia and 3 minutes after. Subsequently, a 20-minute forearm ischemia period was completed. Further, vascular function assessments were completed 15, 30 and 45 minutes into recovery. Flow-mediated dilation, low-flow-mediated constriction, and reactive hyperaemia proximal to the area of ischemia were determined. Flow-mediated dilation was reduced at 15 minutes of recovery but recovered at 30 and 45 minutes (PRE: 7.1±1.0%, POST15∶4.5±0.6%, POST30∶5. 5±0.7% POST45∶5.9±0.4%, p<0.01. Conversely, low-flow mediated constriction increased (PRE: -1.3±0.4%, POST15: -3.3±0.6%, POST30: -2.5±0.5% POST45: -1.5±0.12%, p<0.01. Reactive hyperaemia was reduced throughout recovery (p<0.05. Data were unaffected by menstrual phase. Prolonged low flow altered vascular function and may relate as much to increased vasoconstriction as with decreased vasodilation. Reductions in anterograde shear and greater retrograde shear likely modulate the brachial artery response, but the reduced total shear also plays an important role. The data suggest substantial alterations in vascular function proximal to areas of ischemia with potential clinical implications following reperfusion.

  12. Glucose Sensing

    CERN Document Server

    Geddes, Chris D

    2006-01-01

    Topics in Fluorescence Spectroscopy, Glucose Sensing is the eleventh volume in the popular series Topics in Fluorescence Spectroscopy, edited by Drs. Chris D. Geddes and Joseph R. Lakowicz. This volume incorporates authoritative analytical fluorescence-based glucose sensing reviews specialized enough to be attractive to professional researchers, yet also appealing to the wider audience of scientists in related disciplines of fluorescence. Glucose Sensing is an essential reference for any lab working in the analytical fluorescence glucose sensing field. All academics, bench scientists, and industry professionals wishing to take advantage of the latest and greatest in the continuously emerging field of glucose sensing, and diabetes care & management, will find this volume an invaluable resource. Topics in Fluorescence Spectroscopy Volume 11, Glucose Sensing Chapters include: Implantable Sensors for Interstitial Fluid Smart Tattoo Glucose Sensors Optical Enzyme-based Glucose Biosensors Plasmonic Glucose Sens...

  13. Persistent oxygen-glucose deprivation induces astrocytic death through two different pathways and calpain-mediated proteolysis of cytoskeletal proteins during astrocytic oncosis.

    Science.gov (United States)

    Cao, Xu; Zhang, Ying; Zou, Liangyu; Xiao, Haibing; Chu, Yinghao; Chu, Xiaofan

    2010-07-26

    Astrocytes are thought to play a role in the maintenance of homeostasis and the provision of metabolic substrates for neurons as well as the coupling of cerebral blood flow to neuronal activity. Accordingly, astrocytic death due to various types of injury can critically influence neuronal survival. The exact pathway of cell death after brain ischemia is under debate. In the present study, we used astrocytes from rat primary culture treated with persistent oxygen-glucose-deprivation (OGD) as a model of ischemia to examine the pathway of cell death and the relevant mechanisms. We observed changes in the cellular morphology, the energy metabolism of astrocytes, and the percentage of apoptosis or oncosis of the astrocytes induced by OGD. Electron microscopy revealed the co-existence of ultrastructural features in both apoptosis and oncosis in individual cells. The cellular ATP content was gradually decreased and the percentages of apoptotic and oncotic cells were increased during OGD. After 4h of OGD, ATP depletion to less than 35% of the control was observed, and oncosis became the primary pathway for astrocytic death. Increased plasma membrane permeability due to oncosis was associated with increased calpain-mediated degradation of several cytoskeletal proteins, including paxillin, vinculin, vimentin and GFAP. Pre-treatment with the calpain inhibitor 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) could delay the OGD-induced astrocytic oncosis. These results suggest that there is a narrow range of ATP that determines astrocytic oncotic death induced by persistent OGD and that calpain-mediated hydrolysis of the cytoskeletal-associated proteins may contribute to astrocytes oncosis.

  14. Enhancement of LPS-Induced Microglial Inflammation Response via TLR4 Under High Glucose Conditions

    Directory of Open Access Journals (Sweden)

    Xiang Zhang

    2015-03-01

    Full Text Available Background: Microglia activation mediated by toll-like receptor 4 (TLR4 plays an important role in neuroinflammation and postoperative cognitive dysfunction (POCD. Diabetes mellitus (DM has been recently suggested as an independent risk factor for POCD. In this study, we investigate the potential exacerbation of the inflammatory response in primary microglia due to high glucose conditions. Methods: Primary microglial cells were exposed to normal glucose (25 mmol/L and high glucose (35 mmol/L levels alone or with lipopolyscaccharide (LPS 0, 2, 5, 10 ng/mL. The pro-inflammatory response of the cells was assessed by measuring changes in cytokine levels and the evaluation of associated signaling pathways. Results: Neither high glucose nor low LPS (≤5ng/ml alone had an effect on TNF-a and IL-6 levels, but the combination of low LPS and high glucose stimulated the inflammatory response. Analyses of the associated signaling pathways demonstrated that high glucose enhanced the LPS-induced microglial activation via the TLR4/JAK2/STAT3 pathway. Conclusion: This study demonstrates that high glucose, one of the key abnormalities characteristic of DM, can augment LPS-induced microglial activation and inflammatory cytokine levels through the TLR4/JAK2/STAT3 pathway, offering new insight into the pathophysiological relationship between DM and POCD.

  15. Sonic Hedgehog Signaling Mediates Resveratrol to Increase Proliferation of Neural Stem Cells After Oxygen-Glucose Deprivation/Reoxygenation Injury in Vitro

    Directory of Open Access Journals (Sweden)

    Wei Cheng

    2015-03-01

    Full Text Available Background/Aims: There is interest in drugs and rehabilitation methods to enhance neurogenesis and improve neurological function after brain injury or degeneration. Resveratrol may enhance hippocampal neurogenesis and improve hippocampal atrophy in chronic fatigue mice and prenatally stressed rats. However, its effect and mechanism of neurogenesis after stroke is less well understood. Sonic hedgehog (Shh signaling is crucial for neurogenesis in the embryonic and adult brain, but relatively little is known about the role of Shh signaling in resveratrol-enhanced neurogenesis after stroke. Methods: Neural stem cells (NSCs before oxygen-glucose deprivation/reoxygenation (OGD/R in vitro were pretreated with resveratrol with or without cyclopamine. Survival and proliferation of NSCs was assessed by the CCK8 assay and BrdU immunocytochemical staining. The expressions and activity of signaling proteins and mRNAs were detected by immunocytochemistry, Western blotting, and RT-PCR analysis. Results: Resveratrol significantly increased NSCs survival and proliferation in a concentration-dependent manner after OGD/R injury in vitro. At the same time, the expression of Patched-1, Smoothened (Smo, and Gli-1 proteins and mRNAs was upregulated, and Gli-1 entered the nucleus, which was inhibited by cyclopamine, a Smo inhibitor. Conclusion: Shh signaling mediates resveratrol to increase NSCs proliferation after OGD/R injury in vitro.

  16. Proteomic Identification of Nrf2-Mediated Phase II Enzymes Critical for Protection of Tao Hong Si Wu Decoction against Oxygen Glucose Deprivation Injury in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Hong-yi Qi

    2014-01-01

    Full Text Available Chinese herbal medicine formula Tao Hong Si Wu decoction (THSWD is traditionally used in China for cerebrovascular diseases. However, the molecular mechanisms of THSWD associated with the cerebral ischemia reperfusion injury are largely unknown. The current study applied the two-dimensional gel electrophoresis-based proteomics to investigate the different protein profiles in PC12 cells with and without the treatment of THSWD. Twenty-six proteins affected by THSWD were identified by MALDI-TOF mass spectrometry. Gene ontology analysis showed that those proteins participated in several important biological processes and exhibited diverse molecular functions. In particular, six of them were found to be phase II antioxidant enzymes, which were regulated by NF-E2-related factor-2 (Nrf2. Quantitative PCR further confirmed a dose-dependent induction of the six phase II enzymes by THSWD at the transcription level. Moreover, the individual ingredients of THSWD were discovered to synergistically contribute to the induction of phase II enzymes. Importantly, THSWD’s protection against oxygen-glucose deprivation-reperfusion (OGD-Rep induced cell death was significantly attenuated by antioxidant response element (ARE decoy oligonucleotides, suggesting the protection of THSWD may be likely regulated at least in part by Nrf2-mediated phase II enzymes. Thus, our data will help to elucidate the molecular mechanisms underlying the neuroprotective effect of THSWD.

  17. Creating augmented reality

    OpenAIRE

    Kuusisto, Raine

    2015-01-01

    Augmented reality (AR) is used in different occasions in our daily lives. The idea of an electronic display and spectacles that overlays data to people came in 1901. Augmented reality revolution started in 1990, it is a combination of real life and virtual reality. The beginning of AR is being examined from the very beginning of it. In 1999, it gained momentum when Hirokazu Kato published the ARToolkit to the open source community. After this, augmented reality has evolved everywhere, includi...

  18. Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Chatterjee S

    2015-08-01

    Full Text Available Sushmita Chatterjee, Nirmal Thaker, Abhijit DeMolecular Functional Imaging Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, IndiaAbstract: Radiosensitization using either metformin or 2-deoxy-d-glucose (2-DG in various cancer cells has been reported. The present study reveals novel information on combining these drugs to enhance radiosensitization effect in breast cancer (BC cells. Responses to low-dose Cobalt60 radiation, as well as a newly emerged radioiodine therapy target for BC, that is, sodium-iodide symporter (NIS or SLC5A5 protein, are tested. As therapeutic potential of NIS in BC is often limited due to low uptake and fast efflux rate of iodine, the scope of these two radiosensitizers to further improve NIS-mediated 131I therapeutic efficacy is explored. Two BC cell lines, MCF-7, and MDA MB231 are tested to optimize minimal drug doses required for radiosensitization. A combination of 2 mM metformin and 20 mM 2-DG with 2 grey (Gy Cobalt60 radiation shows significant radiosensitization effect (P=0.0002. In cells treated with the combination therapy, increased γH2A.X foci formation was noted. Further, MCF-7 BC cells overexpressing NIS (MCF-7 NIS was established, and using the optimized drug concentrations, significant radiosensitization (P=0.0019 by 50 µ Ci 131I usage was found to be the case as well. Apoptosis data corroborates with the result of clonogenic assay showing significant increase in apoptotic population upon dual drug-mediated radiosensitization. In case of metformin treatment, lowered adenosine triphosphate (ATP content of the cell has been observed. The encouraging radiosensitization effect observed using combined 2-DG and metformin may aid in reducing Cobalt60 radiation exposure or for targeted radioiodine therapy in BC cells with NIS expression. This study indicates high potential of this drug combination in sensitizing BC cells for NIS-mediated

  19. Mobile Augmented Reality Applications

    CERN Document Server

    Prochazka, David; Popelka, Ondrej; Stastny, Jiri

    2011-01-01

    Augmented reality have undergone considerable improvement in past years. Many special techniques and hardware devices were developed, but the crucial breakthrough came with the spread of intelligent mobile phones. This enabled mass spread of augmented reality applications. However mobile devices have limited hardware capabilities, which narrows down the methods usable for scene analysis. In this article we propose an augmented reality application which is using cloud computing to enable using of more complex computational methods such as neural networks. Our goal is to create an affordable augmented reality application suitable which will help car designers in by 'virtualizing' car modifications.

  20. Portal vein glucose entry triggers a coordinated cellular response that potentiates hepatic glucose uptake and storage in normal but not high-fat/high-fructose-fed dogs.

    Science.gov (United States)

    Coate, Katie C; Kraft, Guillaume; Irimia, Jose M; Smith, Marta S; Farmer, Ben; Neal, Doss W; Roach, Peter J; Shiota, Masakazu; Cherrington, Alan D

    2013-02-01

    The cellular events mediating the pleiotropic actions of portal vein glucose (PoG) delivery on hepatic glucose disposition have not been clearly defined. Likewise, the molecular defects associated with postprandial hyperglycemia and impaired hepatic glucose uptake (HGU) following consumption of a high-fat, high-fructose diet (HFFD) are unknown. Our goal was to identify hepatocellular changes elicited by hyperinsulinemia, hyperglycemia, and PoG signaling in normal chow-fed (CTR) and HFFD-fed dogs. In CTR dogs, we demonstrated that PoG infusion in the presence of hyperinsulinemia and hyperglycemia triggered an increase in the activity of hepatic glucokinase (GK) and glycogen synthase (GS), which occurred in association with further augmentation in HGU and glycogen synthesis (GSYN) in vivo. In contrast, 4 weeks of HFFD feeding markedly reduced GK protein content and impaired the activation of GS in association with diminished HGU and GSYN in vivo. Furthermore, the enzymatic changes associated with PoG sensing in chow-fed animals were abolished in HFFD-fed animals, consistent with loss of the stimulatory effects of PoG delivery. These data reveal new insight into the molecular physiology of the portal glucose signaling mechanism under normal conditions and to the pathophysiology of aberrant postprandial hepatic glucose disposition evident under a diet-induced glucose-intolerant condition.

  1. Intranasal administration of HIV-DNA vaccine formulated with a polymer, carboxymethylcellulose, augments mucosal antibody production and cell-mediated immune response.

    Science.gov (United States)

    Hamajima, K; Sasaki, S; Fukushima, J; Kaneko, T; Xin, K Q; Kudoh, I; Okuda, K

    1998-08-01

    We previously reported that intramuscular (i.m.) immunization of DNA vaccine encoding human immunodeficiency virus type 1 (HIV-1)IIIB env and rev genes alone or in combination with appropriate adjuvant induces substantial and enhanced immune response against HIV-1. In the present study, we examined whether a polymer, low-viscosity carboxymethylcellulose sodium salt (CMCS-L), has an adjuvant effect on immune response induced by DNA vaccination. BALB/c mice were immunized with HIV-DNA vaccine formulated with CMCS-L via the intranasal (i.n.) and i.m. routes. The combination with the polymer elicited higher levels of antigen-specific serum IgG and fecal IgA antibodies than DNA vaccine alone. For cell-mediated immunity, HIV-specific delayed-type hypersensitivity response and cytotoxic T lymphocyte activity were measured by the footpad-swelling test and the 51Cr-release assay, respectively. Both were enhanced by the combination with CMCS-L via i.n. and i.m. inoculation. Cytokine analysis in culture media of bulk splenocytes harvested from immunized animals showed higher levels of IL-4 production in i.n. -immunized mice compared with i.m.-immunized mice. Nevertheless, the increased IFN-gamma production resulting from the combination with CMCS-L was observed only in i.n.-immunized mice. These data indicate that i.n. immunization of HIV-DNA vaccine formulated with CMCS-L enhances HIV-specific mucosal antibody (Ab) and systemic Ab and cell-mediated immune response.

  2. 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-D-pyranoside confers neuroprotection in cell and animal models of ischemic stroke through calpain1/PKA/CREB-mediated induction of neuronal glucose transporter 3

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Shu; Cheng, Qiong; Li, Lu; Liu, Mei; Yang, Yumin; Ding, Fei, E-mail: dingfei@ntu.edu.cn

    2014-06-15

    Salidroside is proven to be a neuroprotective agent of natural origin, and its analog, 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-D-pyranoside (named SalA-4 g), has been synthesized in our lab. In this study, we showed that SalA-4 g promoted neuronal survival and inhibited neuronal apoptosis in primary hippocampal neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to ischemia by transient middle cerebral artery occlusion (MCAO), respectively, and that SalA-4 g was more neuroprotective than salidroside. We further found that SalA-4 g elevated glucose uptake in OGD-injured primary hippocampal neurons and increased the expression and recruitment of glucose transporter 3 (GLUT3) in ischemic brain. Signaling analysis revealed that SalA-4 g triggered the phosphorylation of CREB, and increased the expression of PKA RII in primary hippocampal neurons exposed to OGD injury, while inhibition of PKA/CREB by H-89 alleviated the elevation in glucose uptake and GLUT3 expression, and blocked the protective effects of SalA-4 g. Moreover, SalA-4 g was noted to inhibit intracellular Ca{sup 2+} influx and calpain1 activation in OGD-injured primary hippocampal neurons. Our results suggest that SalA-4 g neuroprotection might be mediated by increased glucose uptake and elevated GLUT3 expression through calpain1/PKA/CREB pathway. - Highlights: • A salidroside (Sal) analog (SalA-4 g) is prepared to be more neuroprotective than Sal. • SalA-4 g protected hippocampal neurons from oxygen and glucose deprivation insult. • SalA-4 g reduced ischemic injury after transient middle cerebral artery occlusion in rats. • Neuroprotection of SalA-4 g was mediated by GLUT3 level via calpain/PKA/CREB pathway.

  3. Serotonin mediates rapid changes of striatal glucose and lactate metabolism after systemic 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") administration in awake rats

    DEFF Research Database (Denmark)

    Gramsbergen, Jan Bert; Cumming, Paul

    2007-01-01

    metabolism in freely moving rats using rapid sampling microdialysis (every minute) coupled to flow-injection analysis (FIA) with biosensors for glucose and lactate. Blood samples for analysis of glucose and lactate were taken at 30-45 min intervals before and after drug dosing and body temperature...... The pathway for selective serotonergic toxicity of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is poorly understood, but has been linked to hyperthermia and disturbed energy metabolism. We investigated the dose-dependency and time-course of MDMA-induced perturbations of cerebral glucose...... depletions of striatal serotonin. Blood glucose and lactate levels were also transiently elevated (163 and 135%) at the highest MDMA doses. The blood glucose rises were significantly related to brain glucose and brain lactate changes. The metabolic perturbations in striatum and the hyperthermic response (+1...

  4. Confronting an Augmented Reality

    Science.gov (United States)

    Munnerley, Danny; Bacon, Matt; Wilson, Anna; Steele, James; Hedberg, John; Fitzgerald, Robert

    2012-01-01

    How can educators make use of augmented reality technologies and practices to enhance learning and why would we want to embrace such technologies anyway? How can an augmented reality help a learner confront, interpret and ultimately comprehend reality itself ? In this article, we seek to initiate a discussion that focuses on these questions, and…

  5. Confronting an Augmented Reality

    Science.gov (United States)

    Munnerley, Danny; Bacon, Matt; Wilson, Anna; Steele, James; Hedberg, John; Fitzgerald, Robert

    2012-01-01

    How can educators make use of augmented reality technologies and practices to enhance learning and why would we want to embrace such technologies anyway? How can an augmented reality help a learner confront, interpret and ultimately comprehend reality itself ? In this article, we seek to initiate a discussion that focuses on these questions, and…

  6. Augmented Spinor Space

    Institute of Scientific and Technical Information of China (English)

    Xiuhong FENG; Lin ZHU; Yanlin YU

    2007-01-01

    In this paper, based on the Pauli matrices, a notion of augmented spinor space is introduced, and a uniqueness of such augmented spinor space of rank n is proved. It may be expected that this new notion of spaces can be used in mathematical physics and geometry.

  7. Disulfiram/copper causes redox-related proteotoxicity and concomitant heat shock response in ovarian cancer cells that is augmented by auranofin-mediated thioredoxin inhibition

    Science.gov (United States)

    Papaioannou, Margarita; Mylonas, Ioannis; Kast, Richard E.; Brüning, Ansgar

    2014-01-01

    A valuable strategy to develop new therapeutic options for a variety of diseases has been the identification of new targets and applications for already approved drugs, the so-called drug repositioning. Recurrent ovarian cancer is a nearly incurable malignancy for which new and effective treatments are urgently needed. The alcohol-deterring drug disulfiram has been shown to cause preferential cell death in a variety of cancer cells. In this study, it is shown that disulfiram mediates effective cell death in ovarian cancer cells by promoting a pro-oxidative intracellular environment in a copper-dependent mechanism. Within few hours of application, disulfiram caused irreversible cell damage associated with pronounced induction of the inducible heat shock proteins HSP70, HSP40, and HSP32. The small heat shock protein HSP27 was found to be covalently dimerized via oxidized disulfide bonds and precipitated in para-nuclear protein aggregates. Simultaneous inhibition of the cellular thioredoxin system by auranofin further enhanced the cytotoxic effect of disulfiram. These data indeed indicate that the combination of two approved drugs, the anti-alcoholic disulfiram and the anti-rheumatic auranofin, may be of interest for the treatment of recurrent and genotoxic drug-resistant ovarian cancer by inducing a proteotoxic cell death mechanism. PMID:25593981

  8. Repeated whole cigarette smoke exposure alters cell differentiation and augments secretion of inflammatory mediators in air-liquid interface three-dimensional co-culture model of human bronchial tissue.

    Science.gov (United States)

    Ishikawa, Shinkichi; Ito, Shigeaki

    2017-02-01

    In vitro models of human bronchial epithelium are useful for toxicological testing because of their resemblance to in vivo tissue. We constructed a model of human bronchial tissue which has a fibroblast layer embedded in a collagen matrix directly below a fully-differentiated epithelial cell layer. The model was applied to whole cigarette smoke (CS) exposure repeatedly from an air-liquid interface culture while bronchial epithelial cells were differentiating. The effects of CS exposure on differentiation were determined by histological and gene expression analyses on culture day 21. We found a decrease in ciliated cells and perturbation of goblet cell differentiation. We also analyzed the effects of CS exposure on the inflammatory response, and observed a significant increase in secretion of IL-8, GRO-α, IL-1β, and GM-CSF. Interestingly, secretion of these mediators was augmented with repetition of whole CS exposure. Our data demonstrate the usefulness of our bronchial tissue model for in vitro testing and the importance of exposure repetition in perturbing the differentiation and inflammation processes.

  9. Inhibition of mTOR pathway restrains astrocyte proliferation, migration and production of inflammatory mediators after oxygen-glucose deprivation and reoxygenation.

    Science.gov (United States)

    Li, Chun-Yu; Li, Xiao; Liu, Shuang-Feng; Qu, Wen-Sheng; Wang, Wei; Tian, Dai-Shi

    2015-01-01

    Glial scar is a major impediment to axonal regeneration in central nervous system (CNS) disorders. Overcoming this physical and biochemical barrier might be crucial for axonal regeneration and functional compensation during the progression of CNS disorders. The mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase, involved in process of cell proliferation, migration, autophagy and protein synthesis. Rapamycin, an inhibitor of mTOR signaling, can exert neuroprotective effects in several CNS diseases. However, its role in the process of reactive astrogliosis including cell proliferation, migration and cytokine production after cerebral ischemia still remains largely unknown. In this study, we investigated the effects of mTOR blockade in cultured astrocytes exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), a wildly used cellular ischemia model which mimics ideally cerebral ischemia model in vivo. We found that astrocytes became activated after OGD/R, characterized by change of astrocytic morphology, upregulation of GFAP expression, the increase number of Edu positive cells, and accompanied with phosphorylation of mTOR protein and its substrate S6K1. Rapamycin significantly inhibited mTOR signal pathway, suppressed proliferation of astrocytes via modulation of cell cycle progression. Moreover, rapamycin attenuated astrocytic migration and mitigated production of inflammatory factors such as TNF-α and iNOS induced by astrocytes exposed to OGD/R. Taken together, our findings indicated that mTOR blockade by rapamycin attenuates astrocyte migration, proliferation and production of inflammation mediators. We suggest that targeting mTOR pathway in astrocyte activation may represent a potentially new therapeutic strategy against deleterious neurotoxic processes of reactive astrogliosis in CNS disorders such as ischemic stroke.

  10. Oxygen/glucose deprivation induces a reduction in synaptic AMPA receptors on hippocampal CA3 neurons mediated by mGluR1 and adenosine A3 receptors.

    Science.gov (United States)

    Dennis, Siobhan H; Jaafari, Nadia; Cimarosti, Helena; Hanley, Jonathan G; Henley, Jeremy M; Mellor, Jack R

    2011-08-17

    Hippocampal CA1 pyramidal neurons are highly sensitive to ischemic damage, whereas neighboring CA3 pyramidal neurons are less susceptible. It is proposed that switching of AMPA receptor (AMPAR) subunits on CA1 neurons during an in vitro model of ischemia, oxygen/glucose deprivation (OGD), leads to an enhanced permeability of AMPARs to Ca(2+), resulting in delayed cell death. However, it is unclear whether the same mechanisms exist in CA3 neurons and whether this underlies the differential sensitivity to ischemia. Here, we investigated the consequences of OGD for AMPAR function in CA3 neurons using electrophysiological recordings in rat hippocampal slices. Following a 15 min OGD protocol, a substantial depression of AMPAR-mediated synaptic transmission was observed at CA3 associational/commissural and mossy fiber synapses but not CA1 Schaffer collateral synapses. The depression of synaptic transmission following OGD was prevented by metabotropic glutamate receptor 1 (mGluR1) or A(3) receptor antagonists, indicating a role for both glutamate and adenosine release. Inhibition of PLC, PKC, or chelation of intracellular Ca(2+) also prevented the depression of synaptic transmission. Inclusion of peptides to interrupt the interaction between GluA2 and PICK1 or dynamin and amphiphysin prevented the depression of transmission, suggesting a dynamin and PICK1-dependent internalization of AMPARs after OGD. We also show that a reduction in surface and total AMPAR protein levels after OGD was prevented by mGluR1 or A(3) receptor antagonists, indicating that AMPARs are degraded following internalization. Thus, we describe a novel mechanism for the removal of AMPARs in CA3 pyramidal neurons following OGD that has the potential to reduce excitotoxicity and promote neuroprotection.

  11. Oxygen/glucose Deprivation Induces a Reduction in Synaptic AMPA Receptors on Hippocampal CA3 Neurons Mediated by mGluR1 and A3 Receptors

    Science.gov (United States)

    Dennis, Siobhan H.; Jaafari, Nadia; Cimarosti, Helena; Hanley, Jonathan G.; Henley, Jeremy M.; Mellor, Jack R.

    2011-01-01

    Summary Hippocampal CA1 pyramidal neurons are highly sensitive to ischemic damage, whereas neighbouring CA3 pyramidal neurons are less susceptible. It is proposed that switching of AMPA receptor (AMPAR) subunits on CA1 neurons during an in vitro model of ischemia, oxygen/glucose deprivation (OGD), leads to an enhanced permeability of AMPARs to Ca2+ resulting in delayed cell death. However, it is unclear if the same mechanisms exist in CA3 neurons and whether this underlies the differential sensitivity to ischemia. Here, we investigated the consequences of OGD for AMPAR function in CA3 neurons using electrophysiological recordings in rat hippocampal slices. Following a 15 minute OGD protocol a substantial depression of AMPAR-mediated synaptic transmission was observed at CA3 associational/commissural and mossy fiber synapses but not CA1 Schaffer collateral synapses. The depression of synaptic transmission following OGD was prevented by mGluR1 or A3 receptor antagonists, indicating a role for both glutamate and adenosine release. Inhibition of PLC, PKC or chelation of intracellular Ca2+ also prevented the depression of synaptic transmission. Inclusion of peptides to interrupt the interaction between GluA2 and PICK1 or dynamin and amphiphysin prevented the depression of transmission, suggesting a dynamin and PICK1-dependent internalisation of AMPARs after OGD. We also show a reduction in surface and total AMPAR protein levels after OGD was prevented by mGluR1 or A3 receptor antagonists indicating that AMPARs are degraded following internalisation. Thus, we describe a novel mechanism for the removal of AMPARs in CA3 pyramidal neurons following OGD that has the potential to reduce excitotoxicity and promote neuroprotection. PMID:21849555

  12. Melatonin-Mediated Intracellular Insulin during 2-Deoxy-d-glucose Treatment Is Reduced through Autophagy and EDC3 Protein in Insulinoma INS-1E Cells

    Directory of Open Access Journals (Sweden)

    Han Sung Kim

    2016-01-01

    Full Text Available 2-DG triggers glucose deprivation without altering other nutrients or metabolic pathways and then activates autophagy via activation of AMPK and endoplasmic reticulum (ER stress. We investigated whether 2-DG reduced intracellular insulin increased by melatonin via autophagy/EDC3 in insulinoma INS-1E cells. p-AMPK and GRP78/BiP level were significantly increased by 2-DG in the presence/absence of melatonin, but IRE1α level was reduced in 2-DG treatment. Levels of p85α, p110, p-Akt (Ser473, Thr308, and p-mTOR (Ser2481 were also significantly reduced by 2-DG in the presence/absence of melatonin. Mn-SOD increased with 2-DG plus melatonin compared to groups treated with/without melatonin alone. Bcl-2 was decreased and Bax increased with 2-DG plus melatonin. LC3II level increased with 2-DG treatment in the presence/absence of melatonin. Intracellular insulin production increased in melatonin plus 2-DG but reduced in treatment with 2-DG with/without melatonin. EDC3 was increased by 2-DG in the presence/absence of melatonin. Rapamycin, an mTOR inhibitor, increased GRP78/BiP and EDC3 levels in a dose-dependent manner and subsequently resulted in a decrease in intracellular production of insulin. These results suggest that melatonin-mediated insulin synthesis during 2-DG treatment involves autophagy and EDC3 protein in rat insulinoma INS-1E cells and subsequently results in a decrease in intracellular production of insulin.

  13. SLC25A23 augments mitochondrial Ca²⁺ uptake, interacts with MCU, and induces oxidative stress-mediated cell death.

    Science.gov (United States)

    Hoffman, Nicholas E; Chandramoorthy, Harish C; Shanmughapriya, Santhanam; Zhang, Xueqian Q; Vallem, Sandhya; Doonan, Patrick J; Malliankaraman, Karthik; Guo, Shuchi; Rajan, Sudarsan; Elrod, John W; Koch, Walter J; Cheung, Joseph Y; Madesh, Muniswamy

    2014-03-01

    Emerging findings suggest that two lineages of mitochondrial Ca(2+) uptake participate during active and resting states: 1) the major eukaryotic membrane potential-dependent mitochondrial Ca(2+) uniporter and 2) the evolutionarily conserved exchangers and solute carriers, which are also involved in ion transport. Although the influx of Ca(2+) across the inner mitochondrial membrane maintains metabolic functions and cell death signal transduction, the mechanisms that regulate mitochondrial Ca(2+) accumulation are unclear. Solute carriers--solute carrier 25A23 (SLC25A23), SLC25A24, and SLC25A25--represent a family of EF-hand-containing mitochondrial proteins that transport Mg-ATP/Pi across the inner membrane. RNA interference-mediated knockdown of SLC25A23 but not SLC25A24 and SLC25A25 decreases mitochondrial Ca(2+) uptake and reduces cytosolic Ca(2+) clearance after histamine stimulation. Ectopic expression of SLC25A23 EF-hand-domain mutants exhibits a dominant-negative phenotype of reduced mitochondrial Ca(2+) uptake. In addition, SLC25A23 interacts with mitochondrial Ca(2+) uniporter (MCU; CCDC109A) and MICU1 (CBARA1) while also increasing IMCU. In addition, SLC25A23 knockdown lowers basal mROS accumulation, attenuates oxidant-induced ATP decline, and reduces cell death. Further, reconstitution with short hairpin RNA-insensitive SLC25A23 cDNA restores mitochondrial Ca(2+) uptake and superoxide production. These findings indicate that SLC25A23 plays an important role in mitochondrial matrix Ca(2+) influx.

  14. Sustained miRNA-mediated knockdown of mutant AAT with simultaneous augmentation of wild-type AAT has minimal effect on global liver miRNA profiles.

    Science.gov (United States)

    Mueller, Christian; Tang, Qiushi; Gruntman, Alisha; Blomenkamp, Keith; Teckman, Jeffery; Song, Lina; Zamore, Phillip D; Flotte, Terence R

    2012-03-01

    α-1 antitrypsin (AAT) deficiency can exhibit two pathologic states: a lung disease that is primarily due to the loss of AAT's antiprotease function, and a liver disease resulting from a toxic gain-of-function of the PiZ-AAT (Z-AAT) mutant protein. We have developed several recombinant adeno-associated virus (rAAV) vectors that incorporate microRNA (miRNA) sequences targeting the AAT gene while also driving the expression of miRNA-resistant wild-type AAT-PiM (M-AAT) gene, thus achieving concomitant Z-AAT knockdown in the liver and increased expression of M-AAT. Transgenic mice expressing the human PiZ allele treated with dual-function rAAV9 vectors showed that serum PiZ was stably and persistently reduced by an average of 80%. Treated animals showed knockdown of Z-AAT in liver and serum with concomitant increased serum M-AAT as determined by allele-specific enzyme-linked immunosorbent assays (ELISAs). In addition, decreased globular accumulation of misfolded Z-AAT in hepatocytes and a reduction in inflammatory infiltrates in the liver was observed. Results from microarray studies demonstrate that endogenous miRNAs were minimally affected by this treatment. These data suggests that miRNA mediated knockdown does not saturate the miRNA pathway as has been seen with viral vector expression of short hairpin RNAs (shRNAs). This safe dual-therapy approach can be applied to other disorders such as amyotrophic lateral sclerosis, Huntington disease, cerebral ataxia, and optic atrophies.

  15. The PI3K/Akt Signaling Pathway Mediates the High Glucose-Induced Expression of Extracellular Matrix Molecules in Human Retinal Pigment Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Dong Qin

    2015-01-01

    Full Text Available Prolonged hyperglycemia is an important risk factor of the pathogenesis of diabetic retinopathy (DR. Extracellular matrix molecules, such as fibronectin, collagen IV, and laminin, are associated with fibrotic membranes. In this study, we investigated the expression of fibronectin, collagen IV, and laminin in RPE cells under high glucose conditions. Furthermore, we also detected the phosphorylation of protein kinase B (Akt under high glucose conditions in RPE cells. Our results showed that high glucose upregulated fibronectin, collagen IV, and laminin expression, and activated Akt in RPE cells. We also found that pretreatment with LY294002 (an inhibitor of phosphatidylinositol 3-kinase abolished high glucose-induced expression of fibronectin, collagen IV, and laminin in RPE cells. Thus, high glucose induced the expression of fibronectin, collagen IV, and laminin through PI3K/Akt signaling pathway in RPE cells, and the PI3K/Akt signaling pathway may contribute to the formation of fibrotic membrane during the development of DR.

  16. Spleen tyrosine kinase mediates high glucose-induced transforming growth factor-{beta}1 up-regulation in proximal tubular epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Won Seok; Chang, Jai Won [Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of); Han, Nam Jeong [Department of Cell Biology, Asan Institute for Life Sciences, Seoul (Korea, Republic of); Lee, Sang Koo [Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of); Park, Su-Kil, E-mail: skpark@amc.seoul.kr [Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of)

    2012-09-10

    The role of spleen tyrosine kinase (Syk) in high glucose-induced intracellular signal transduction has yet to be elucidated. We investigated whether Syk is implicated in high glucose-induced transforming growth factor-{beta}1 (TGF-{beta}1) up-regulation in cultured human proximal tubular epithelial cells (HK-2 cell). High glucose increased TGF-{beta}1 gene expression through Syk, extracellular signal-regulated kinase (ERK), AP-1 and NF-{kappa}B. High glucose-induced AP-1 DNA binding activity was decreased by Syk inhibitors and U0126 (an ERK inhibitor). Syk inhibitors suppressed high glucose-induced ERK activation, whereas U0126 had no effect on Syk activation. High glucose-induced NF-{kappa}B DNA binding activity was also decreased by Syk inhibitors. High glucose increased nuclear translocation of p65 without serine phosphorylation of I{kappa}B{alpha} and without degradation of I{kappa}B{alpha}, but with an increase in tyrosine phosphorylation of I{kappa}B{alpha} that may account for the activation of NF-{kappa}B. Both Syk inhibitors and Syk-siRNA attenuated high glucose-induced I{kappa}B{alpha} tyrosine phosphorylation and p65 nuclear translocation. Depletion of p21-activated kinase 2 (Pak2) by transfection of Pak2-siRNA abolished high glucose-induced Syk activation. In summary, high glucose-induced TGF-{beta}1 gene transcription occurred through Pak2, Syk and subsequent ERK/AP-1 and NF-{kappa}B pathways. This suggests that Syk might be implicated in the diabetic kidney disease.

  17. Augmented reality: a review.

    Science.gov (United States)

    Berryman, Donna R

    2012-01-01

    Augmented reality is a technology that overlays digital information on objects or places in the real world for the purpose of enhancing the user experience. It is not virtual reality, that is, the technology that creates a totally digital or computer created environment. Augmented reality, with its ability to combine reality and digital information, is being studied and implemented in medicine, marketing, museums, fashion, and numerous other areas. This article presents an overview of augmented reality, discussing what it is, how it works, its current implementations, and its potential impact on libraries.

  18. A Survey on Applications of Augmented Reality

    Directory of Open Access Journals (Sweden)

    Andrea Sanna

    2016-01-01

    Full Text Available The term Augmented Reality (AR refers to a set of technologies and devices able to enhance and improve human perception, thus bridging the gap between real and virtual space. Physical and artificial objects are mixed together in a hybrid space where the user can move without constraints. This mediated reality is spread in our everyday life: work, study, training, relaxation, time spent traveling are just some of the moments in which you can use AR applications.This paper aims to provide an overview of current technologies and future trends of augmented reality as well as to describe the main application domains, outlining benefits and open issues.

  19. Integrated sensor-augmented pump therapy systems [the MiniMed® Paradigm™ Veo system and the Vibe™ and G4® PLATINUM CGM (continuous glucose monitoring) system] for managing blood glucose levels in type 1 diabetes: A systematic review and economic evaluation

    NARCIS (Netherlands)

    R. Riemsma; I. Corro Ramos (Isaac); R. Birnie (Richard); N. Büyükkaramikli (Nasuh); N. Armstrong (Nigel); S. Ryder; S. Duffy (Steven); G. Worthy (Gill); M.J. Al (Maiwenn); J. Severens (Johan); J. Kleijnen (Jos)

    2016-01-01

    textabstractBackground: In recent years, meters for continuous monitoring of interstitial fluid glucose have been introduced to help people with type 1 diabetes mellitus (T1DM) to achieve better control of their disease. Objective: The objective of this project was to summarise the evidence on the c

  20. Impact of L-FABP and glucose on polyunsaturated fatty acid induction of PPARα-regulated β-oxidative enzymes.

    Science.gov (United States)

    Petrescu, Anca D; Huang, Huan; Martin, Gregory G; McIntosh, Avery L; Storey, Stephen M; Landrock, Danilo; Kier, Ann B; Schroeder, Friedhelm

    2013-02-01

    Liver fatty acid binding protein (L-FABP) is the major soluble protein that binds very-long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) in hepatocytes. However, nothing is known about L-FABP's role in n-3 PUFA-mediated peroxisome proliferator activated receptor-α (PPARα) transcription of proteins involved in long-chain fatty acid (LCFA) β-oxidation. This issue was addressed in cultured primary hepatocytes from wild-type, L-FABP-null, and PPARα-null mice with these major findings: 1) PUFA-mediated increase in the expression of PPARα-regulated LCFA β-oxidative enzymes, LCFA/LCFA-CoA binding proteins (L-FABP, ACBP), and PPARα itself was L-FABP dependent; 2) PPARα transcription, robustly potentiated by high glucose but not maltose, a sugar not taken up, correlated with higher protein levels of these LCFA β-oxidative enzymes and with increased LCFA β-oxidation; and 3) high glucose altered the potency of n-3 relative to n-6 PUFA. This was not due to a direct effect of glucose on PPARα transcriptional activity nor indirectly through de novo fatty acid synthesis from glucose. Synergism was also not due to glucose impacting other signaling pathways, since it was observed only in hepatocytes expressing both L-FABP and PPARα. Ablation of L-FABP or PPARα as well as treatment with MK886 (PPARα inhibitor) abolished/reduced PUFA-mediated PPARα transcription of these genes, especially at high glucose. Finally, the PUFA-enhanced L-FABP distribution into nuclei with high glucose augmentation of the L-FABP/PPARα interaction reveals not only the importance of L-FABP for PUFA induction of PPARα target genes in fatty acid β-oxidation but also the significance of a high glucose enhancement effect in diabetes.

  1. INFORMATION VIA AUGMENTED

    OpenAIRE

    Tetteh, Sampson

    2015-01-01

    The vast majority of mobile technology today has developed over the past dec-ades. The thirst for information and communication has brought about high data transfer speed on modern mobile handset devices. This makes it possible for Augmented Reality to be used on mobile phones. Vaasa University of Applied Science, Technobothnia science resource center and Lumivaara Museum saw the importance of information and decided to embark on a pilot project where Augmented Reality will not be only us...

  2. Confronting an augmented reality

    Directory of Open Access Journals (Sweden)

    John Hedberg

    2012-08-01

    Full Text Available How can educators make use of augmented reality technologies and practices to enhance learning and why would we want to embrace such technologies anyway? How can an augmented reality help a learner confront, interpret and ultimately comprehend reality itself? In this article, we seek to initiate a discussion that focuses on these questions, and suggest that they be used as drivers for research into effective educational applications of augmented reality. We discuss how multi-modal, sensorial augmentation of reality links to existing theories of education and learning, focusing on ideas of cognitive dissonance and the confrontation of new realities implied by exposure to new and varied perspectives. We also discuss connections with broader debates brought on by the social and cultural changes wrought by the increased digitalisation of our lives, especially the concept of the extended mind. Rather than offer a prescription for augmentation, our intention is to throw open debate and to provoke deep thinking about what interacting with and creating an augmented reality might mean for both teacher and learner.

  3. Salvianolic acid B improves the disruption of high glucose-mediated brain microvascular endothelial cells via the ROS/HIF-1α/VEGF and miR-200b/VEGF signaling pathways.

    Science.gov (United States)

    Yang, Ming-Chao; You, Fu-Li; Wang, Zhe; Liu, Xiang-Nan; Wang, Yan-Feng

    2016-09-06

    The study investigated the roles and mechanisms of Salvianolic acid B (Sal B) on permeability of rat brain microvascular endothelial cells (RBMECs) exposed to high glucose. The results demonstrated that Sal B greatly up-regulated the expression of tight junction (TJ) proteins and decreased the permeability of RBMECs compared with the control group. And the increase of reactive oxidative species (ROS) production, the upregulation of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) protein induced by high glucose were antagonized by Sal B. In addition, a great decrease of microRNA-200b (miR-200b) was observed in the RBMECs under high-glucose condition, which was significantly increased by Sal B pretreatment. And overexpression of miR-200b markedly attenuated the RBMECs permeability and inhibited the expression of VEGF protein by targeting with 3'-UTR of its mRNA. This led to the conclusion that Sal B-mediated improvement of blood-brain barrier dysfunction induced by high-glucose is related to the ROS/HIF-1α/VEGF and miR-200b/VEGF signaling pathways.

  4. Glucose oxidation positively regulates glucose uptake and improves cardiac function recovery after myocardial reperfusion.

    Science.gov (United States)

    Li, Tingting; Xu, Jie; Qin, Xinghua; Hou, Zuoxu; Guo, Yongzheng; Liu, Zhenhua; Wu, Jianjiang; Zheng, Hong; Zhang, Xing; Gao, Feng

    2017-03-21

    Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia/reperfusion injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. Here we found that glucose uptake was remarkably diminished in myocardium following reperfusion in Sprague-Dawley rats as detected by 18F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by 3 folds and GLUT4 translocation remained unchanged compared with those of sham rats. The decreased glucose uptake was accompanied by suppressed glucose oxidation. Interestingly, stimulating glucose oxidation by inhibition of pyruvate dehydrogenase kinase 4 (PDK4), a rate-limiting enzyme for glucose oxidation, increased glucose uptake and alleviated ischemia/reperfusion injury. In vitro data in neonatal myocytes showed that PDK4 overexpression decreased glucose uptake, while its knockdown increased glucose uptake, suggesting a role of PDK4 in regulating glucose uptake. Moreover, inhibition of PDK4 increased myocardial glucose uptake with concomitant enhancement of cardiac insulin sensitivity following myocardial ischemia/reperfusion. These results showed that the suppressed glucose oxidation mediated by PDK4 contributes to the reduced glucose uptake in myocardium following reperfusion, and enhancement of glucose uptake exerts cardioprotection. The findings suggest that stimulating glucose oxidation via PDK4 could be an efficient approach to improve recovery from myocardial ischemia/reperfusion injury. Copyright © 2017, American Journal of Physiology-Endocrinology and Metabolism.

  5. Glucose allostasis

    DEFF Research Database (Denmark)

    Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert

    2003-01-01

    In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy...... individuals with normal glucose tolerance, normoglycemia can always be maintained by compensatorily increasing AIR in response to decreasing M (and vice versa). This has been mathematically described by the hyperbolic relationship between AIR and M and referred to as glucose homeostasis, with glucose...... concentration assumed to remain constant along the hyperbola. Conceivably, glucose is one of the signals stimulating AIR in response to decreasing M. Hypothetically, as with any normally functioning feed-forward system, AIR should not fully compensate for worsening M, since this would remove the stimulus...

  6. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

    Directory of Open Access Journals (Sweden)

    Xiaofei Cheng

    2016-01-01

    Full Text Available Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM. Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9, matrix metalloproteinase 3 (MMP-3, and tissue inhibitor of metalloproteinase 1 (TIMP-1, was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

  7. Sodium-glucose cotransport

    Science.gov (United States)

    Poulsen, Søren Brandt; Fenton, Robert A.; Rieg, Timo

    2017-01-01

    Purpose of review Sodium-glucose cotransporters (SGLTs) are important mediators of glucose uptake across apical cell membranes. SGLT1 mediates almost all sodium-dependent glucose uptake in the small intestine, while in the kidney SGLT2, and to a lesser extent SGLT1, account for more than 90% and nearly 3%, respectively, of glucose reabsorption from the glomerular ultrafiltrate. Although the recent availability of SGLT2 inhibitors for the treatment of diabetes mellitus has increased the number of clinical studies, this review has a focus on mechanisms contributing to the cellular regulation of SGLTs. Recent findings Studies have focused on the regulation of SGLT expression under different physiological/pathophysiological conditions, for example diet, age or diabetes mellitus. Several studies provide evidence of SGLT regulation via cyclic adenosine monophosphate/protein kinase A, protein kinase C, glucagon-like peptide 2, insulin, leptin, signal transducer and activator of transcription-3 (STAT3), phosphoinositide-3 kinase (PI3K)/Akt, mitogen-activated protein kinases (MAPKs), nuclear factor-kappaB (NF-kappaB), with-no-K[Lys] kinases/STE20/SPS1-related proline/alanine-rich kinase (Wnk/SPAK) and regulatory solute carrier protein 1 (RS1) pathways. Summary SGLT inhibitors are important drugs for glycemic control in diabetes mellitus. Although the contribution of SGLT1 for absorption of glucose from the intestine as well as SGLT2/SGLT1 for renal glucose reabsorption has been comprehensively defined, this review provides an up-to-date outline for the mechanistic regulation of SGLT1/SGLT2. PMID:26125647

  8. Everything Augmented: On the Real in Augmented Reality

    Directory of Open Access Journals (Sweden)

    Hanna Schraffenberger

    2014-12-01

    Full Text Available What is augmented in Augmented Reality (AR? In this paper, we review existing opinions and show how little consensus exists on this matter. Subsequently, we approach the question from a theoretical and technology-independent perspective. We identify spatial and content-based relationships between the virtual and the real as being decisive for AR and come to the conclusion that virtual content augments that to which it relates. Subsequently, we categorize different forms of AR based on what is augmented. We distinguish between augmented environments, augmented objects, augmented humans and augmented content and consider the possibility of augmented perception. The categories are illustrated with AR (art works and conceptual differences between them are pointed out. Moreover, we discuss what the real contributes to AR and how it can shape (future AR experiences. A summary of our findings and suggestions for future research and practice, such as research into multimodal and crossmodal AR, conclude the paper.

  9. Hypoxia inducible factor-1alpha mediates protection of DL-3-n-butylphthalide in brain microvascular endothelial cells against oxygen glucose deprivation-induced injury

    Institute of Scientific and Technical Information of China (English)

    Weihong Yang; Ling Li; Ruxun Huang; Zhong Pei; Songjie Liao; Jinsheng Zeng

    2012-01-01

    Studies have demonstrated that DL-3-n-butylphthalide can significantly alleviate oxygen glucose deprivation-induced injury of human umbilical vein endothelial cells at least partly associated with its enhancement on oxygen glucose deprivation -induced hypoxia inducible factor-1α expression. In this study, we hypothesized that DL-3-n-butylphthalide can protect against oxygen glucose deprivation-induced injury of newborn rat brain microvascular endothelial cells by means of upregulating hypoxia inducible factor-1α expression. MTT assay and Hoechst staining results showed that DL-3-n-butylphthalide protected brain microvascular endothelial cells against oxygen glucose deprivation-induced injury in a dose-dependent manner. Western blot and immunofluorescent staining results further confirmed that the protective effect was related to upregulation of hypoxia inducible factor-1α. Real-time RT-PCR reaction results showed that DL-3-n-butylphthalide reduced apoptosis by inhibiting downregulation of pro-apoptotic gene caspase-3 mRNA expression and upregulation of apoptosis-executive protease bcl-2 mRNA expression; however, DL-3-n-butylphthalide had no protective effects on brain microvascular endothelial cells after knockdown of hypoxia inducible factor-1α by small interfering RNA. These findings suggest that DL-3-n-butylphthalide can protect brain microvascular endothelial cells against oxygen glucose deprivation-induced injury by upregulating bcl-2 expression and downregulating caspase-3 expression though hypoxia inducible factor-1α pathway.

  10. Role of Peroxisome Proliferator-Activated Receptor Gamma in Glucose-induced Insulin Secretion

    Institute of Scientific and Technical Information of China (English)

    Ze-Kuan XU; Neng-Guin CHEN; Chang-Yan MA; Zhuo-Xian MENG; Yu-Jie SUN; Xiao HAN

    2006-01-01

    Peroxisome proliferator-activated receptor (PPAR) isoforms (α and γ) are known to be expressed in pancreatic islets as well as in insulin-producing cell lines. Ligands of PPAR have been shown to enhance glucose-induced insulin secretion in rat pancreatic islets. However, their effect on insulin secretion is still unclear. To understand the molecular mechanism by which PPARγ exerts its effect on glucoseinduced insulin secretion, we examined the endogenous activity of PPAR isoforms, and studied the PPARγfunction and its target gene expression in INS-1 cells. We found that: (1) endogenous PPARγ was activated in a ligand-dependent manner in INS-1 cells; (2) overexpression of PPARγ in the absence of PPARγ ligands enhanced glucose-induced insulin secretion, which indicates that the increased glucose-induced insulin secretion is a PPARγ-mediated event; (3) the addition of both PPARγ and retinoid X receptor (RXR) ligands showed a synergistic effect on the augmentation of reporter activity, suggesting that the hetero-dimerization of PPARγand RXR is required for the regulation of the target genes; (4) PPARs upregulated both the glucose transporter 2 (GLUT2) and Cbl-associated protein (CAP) genes in INS-1 cells. Our findings suggest an important mechanistic pathway in which PPARγ enhances glucose-induced insulin secretion by activating the expression of GLUT2 and CAP genes in a ligand-dependent manner.

  11. GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets 1

    DEFF Research Database (Denmark)

    Guan, Xinfu; Stoll, Barbara; Lu, Xiaofeng

    2003-01-01

    or glucose uptake. GLP-2 increased PDV indispensable amino acid uptake by 220% and protein synthesis by 125%, but did not decrease protein breakdown or phenylalanine oxidation. CONCLUSIONS: We conclude that in TPN-fed neonatal pigs, GLP-2 acutely stimulates intestinal blood flow and glucose utilization...... (n = 8) received consecutive intravenous infusions of saline, GLP-2, and GLP-2 plus N(G)-Nitro-L-arginine methyl ester (L-NAME, 50 micromol x kg(-1) x hour(-1)) for 4 hours each. RESULTS: GLP-2 acutely increased portal-drained visceral (PDV) blood flow rate (+25%) and intestinal blood volume (+51......%) in TPN-fed piglets. GLP-2 also increased intestinal constitutive nitric oxide synthase (NOS) activity and endothelial NOS protein abundance. GLP-2 acutely increased PDV glucose uptake (+90%) and net lactate production (+79%). Co-infusion of GLP-2 plus L-NAME did not increase either PDV blood flow rate...

  12. Prototyping Augmented Reality

    CERN Document Server

    Mullen, Tony

    2011-01-01

    Learn to create augmented reality apps using Processing open-source programming language Augmented reality (AR) is used all over, and you may not even realize it. Smartphones overlay data onto live camera views to show homes for sale, restaurants, or historical sites. American football broadcasts use AR to show the invisible first-down line on the field to TV viewers. Nike and Budweiser, among others, have used AR in ads. Now, you can learn to create AR prototypes using 3D data, Processing open-source programming language, and other languages. This unique book is an easy-to-follow guide on how

  13. Augmented marked graphs

    CERN Document Server

    Cheung, King Sing

    2014-01-01

    Petri nets are a formal and theoretically rich model for the modelling and analysis of systems. A subclass of Petri nets, augmented marked graphs possess a structure that is especially desirable for the modelling and analysis of systems with concurrent processes and shared resources.This monograph consists of three parts: Part I provides the conceptual background for readers who have no prior knowledge on Petri nets; Part II elaborates the theory of augmented marked graphs; finally, Part III discusses the application to system integration. The book is suitable as a first self-contained volume

  14. Collaboration in Augmented Reality

    OpenAIRE

    Lukosch, S.; Billinghurst, M; Alem, L.; Kiyokawa, K.

    2015-01-01

    Augmented Reality (AR) is a technology that allows users to view and interact in real time with virtual images seamlessly superimposed over the real world. AR systems can be used to create unique collaborative experiences. For example, co-located users can see shared 3D virtual objects that they interact with, or a user can annotate the live video view of a remote worker, enabling them to collaborate at a distance. The overall goal is to augment the face-to-face collaborative experience, or t...

  15. Augmented reality som wearable

    DEFF Research Database (Denmark)

    Buhl, Mie; Rahn, Annette

    2015-01-01

    Artiklen omhandler design og implementering af Augmented Reality (AR) i form af en wearable i sygeplejerskeuddannelsens anatomiundervisning, mere specifikt undervisning i lungeanatomi og respiration, med fokus på potentialer for visuel læring. Projektet undersøger, hvordan en udviklet AR-applikat......Artiklen omhandler design og implementering af Augmented Reality (AR) i form af en wearable i sygeplejerskeuddannelsens anatomiundervisning, mere specifikt undervisning i lungeanatomi og respiration, med fokus på potentialer for visuel læring. Projektet undersøger, hvordan en udviklet AR...

  16. Towards Pervasive Augmented Reality: Context-Awareness in Augmented Reality.

    Science.gov (United States)

    Grubert, Jens; Langlotz, Tobias; Zollmann, Stefanie; Regenbrecht, Holger

    2017-06-01

    Augmented Reality is a technique that enables users to interact with their physical environment through the overlay of digital information. While being researched for decades, more recently, Augmented Reality moved out of the research labs and into the field. While most of the applications are used sporadically and for one particular task only, current and future scenarios will provide a continuous and multi-purpose user experience. Therefore, in this paper, we present the concept of Pervasive Augmented Reality, aiming to provide such an experience by sensing the user's current context and adapting the AR system based on the changing requirements and constraints. We present a taxonomy for Pervasive Augmented Reality and context-aware Augmented Reality, which classifies context sources and context targets relevant for implementing such a context-aware, continuous Augmented Reality experience. We further summarize existing approaches that contribute towards Pervasive Augmented Reality. Based our taxonomy and survey, we identify challenges for future research directions in Pervasive Augmented Reality.

  17. Glucose Stimulates GLP-1 Secretion from Isolated Perfused Rat Small Intestine by SGLT1 and GLUT2 Mediated Uptake, Causing V-gated Calcium Channel Activation

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Frost, Charlotte Rasmussen; Svendsen, Berit

    2014-01-01

    substrate, α-MGP, stimulated release (15.7 ± 0.5 vs. 29.4 ± 0.7 pM, P presence of the SGTL1 inhibitor phloridzin (10 μM) (P > 0.05). However, glucose-stimulated GLP-1 secretion was also sensitive to luminal GLUT2...

  18. Reduced early and late phase insulin response to glucose in isolated spiny mouse (Acomys cahirinus) islets: a defective link between glycolysis and adenylate cyclase.

    Science.gov (United States)

    Nesher, R; Abramovitch, E; Cerasi, E

    1989-09-01

    The spiny mouse (Acomys cahirinus) exhibits low insulin responsiveness to glucose with a nearly absent early phase release. The alternative fuel-secretagogue glyceraldehyde (10 mmol/l) produced a maximal early insulin response in rat islets but failed to affect early response in Acomys; however, it potentiated the late insulin response in both species alike. Glucagon (1.5 mumol/l) potentiated the early insulin response to intermediate (8.3 mmol/l) glucose in rat and Acomys islets by two- and four-fold, respectively. Glucose doubled cyclic AMP levels in rat islets but no significant response was noted in Acomys islets. Isobutylmethylxanthine (0.1 mmol/l) and forskolin (25 mumol/l) caused a significant rise in islet cyclic AMP levels in both types of islets; however, neither agent restored the glucose stimulation of cyclic AMP in spiny mouse islets. Forskolin and isobutylmethylxanthine potentiated early and late phase insulin release in both species; however, neither augmented the early response in the Acomys to the degree observed in rat islets. Thus: (1) A deficient link exists in Acomys between glycolysis and subsequent signals. (2) These islets contain a glucose-insensitive adenylate cyclase. (3) The early insulin response may be potentiated by direct activation of adenylate cyclase. (4) The glucose effects on early and late phase insulin release are probably mediated by distinct pathways. (5) In the spiny mouse the signals mediating the early response are deranged to a greater extent than those activating the late phase insulin release.

  19. Augmented Reality i naturfagsundervisningen

    DEFF Research Database (Denmark)

    Radmer, Ole; Surland, Mogens; Nielsen, Birgitte Lund

    2016-01-01

    Augmented Reality (AR) giver ny mulighed for, at elever kan lave undersøgelser i naturfag med enkel teknologi, hvor animationer og simulationer kobles med det virkelige fænomen. I workshoppen kan I afprøve AR eksempler, udviklet i et internationalt EU projekt. Der vil være noget, der direkte kan...

  20. Augmented reality som wearable

    DEFF Research Database (Denmark)

    Buhl, Mie; Rahn, Annette

    2015-01-01

    Artiklen omhandler design og implementering af Augmented Reality (AR) i form af en wearable i sygeplejerskeuddannelsens anatomiundervisning, mere specifikt undervisning i lungeanatomi og respiration, med fokus på potentialer for visuel læring. Projektet undersøger, hvordan en udviklet AR...

  1. Augmented Reality og kulturarv

    DEFF Research Database (Denmark)

    Nielsen, Mikkel Kirkedahl Lysholm

    2013-01-01

    Museerne står overfor at skulle omfavne den digitale kultur i håndteringen af den store mængde viden, institutionerne repræsenterer. Augmented Reality-systemer forbinder ved hjælp af moderne teknologi det virtuelle med det virkelige, og kan derfor synes som en oplagt anvendelsesmulighed i...

  2. Augmented Reality Binoculars.

    Science.gov (United States)

    Oskiper, Taragay; Sizintsev, Mikhail; Branzoi, Vlad; Samarasekera, Supun; Kumar, Rakesh

    2015-05-01

    In this paper we present an augmented reality binocular system to allow long range high precision augmentation of live telescopic imagery with aerial and terrain based synthetic objects, vehicles, people and effects. The inserted objects must appear stable in the display and must not jitter and drift as the user pans around and examines the scene with the binoculars. The design of the system is based on using two different cameras with wide field of view and narrow field of view lenses enclosed in a binocular shaped shell. Using the wide field of view gives us context and enables us to recover the 3D location and orientation of the binoculars much more robustly, whereas the narrow field of view is used for the actual augmentation as well as to increase precision in tracking. We present our navigation algorithm that uses the two cameras in combination with an inertial measurement unit and global positioning system in an extended Kalman filter and provides jitter free, robust and real-time pose estimation for precise augmentation. We have demonstrated successful use of our system as part of information sharing example as well as a live simulated training system for observer training, in which fixed and rotary wing aircrafts, ground vehicles, and weapon effects are combined with real world scenes.

  3. Augmented reality som wearable

    DEFF Research Database (Denmark)

    Buhl, Mie; Rahn, Annette

    2015-01-01

    Artiklen omhandler design og implementering af Augmented Reality (AR) i form af en wearable i sygeplejerskeuddannelsens anatomiundervisning, mere specifikt undervisning i lungeanatomi og respiration, med fokus på potentialer for visuel læring. Projektet undersøger, hvordan en udviklet AR...

  4. Augmented Reality og kulturarv

    DEFF Research Database (Denmark)

    Nielsen, Mikkel Kirkedahl Lysholm

    2013-01-01

    Museerne står overfor at skulle omfavne den digitale kultur i håndteringen af den store mængde viden, institutionerne repræsenterer. Augmented Reality-systemer forbinder ved hjælp af moderne teknologi det virtuelle med det virkelige, og kan derfor synes som en oplagt anvendelsesmulighed i...

  5. Collaboration in Augmented Reality

    NARCIS (Netherlands)

    Lukosch, S.; Billinghurst, M.; Alem, L.; Kiyokawa, K.

    2015-01-01

    Augmented Reality (AR) is a technology that allows users to view and interact in real time with virtual images seamlessly superimposed over the real world. AR systems can be used to create unique collaborative experiences. For example, co-located users can see shared 3D virtual objects that they int

  6. Collaboration in Augmented Reality

    NARCIS (Netherlands)

    Lukosch, S.; Billinghurst, M.; Alem, L.; Kiyokawa, K.

    2015-01-01

    Augmented Reality (AR) is a technology that allows users to view and interact in real time with virtual images seamlessly superimposed over the real world. AR systems can be used to create unique collaborative experiences. For example, co-located users can see shared 3D virtual objects that they int

  7. Collaborative augmented reality environments

    DEFF Research Database (Denmark)

    Büscher, Monika; Christensen, Michael; Grønbæk, Kaj

    2000-01-01

    This paper describes Manufaktur, a prototype of a concept and infrastructure that goes beyond the classical CVE systems toward a collaborative augmented reality environment, where users? documents and objects appear as live representations in a 3D workspace. Manufaktur supports collaborative...

  8. Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate Glut-4, PPAR gamma and PI3K.

    Science.gov (United States)

    Kumar, Ramadhar; Balaji, S; Uma, T S; Sehgal, P K

    2009-12-10

    Momordica charantia fruit is a widely used traditional medicinal herb as, anti-diabetic, anti-HIV, anti-ulcer, anti-inflammatory, anti-leukemic, anti-microbial, and anti-tumor. The present study is undertaken to investigate the possible mode of action of fruit extracts derived from Momordica charantia (MC) and study its pharmacological effects for controlling diabetic mellitus. Effects of aqueous and chloroform extracts of Momordica charantia fruit on glucose uptake and up-regulation of glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPAR gamma) and phosphatidylinositol-3 kinase (PI3K), were investigated to show its efficacy as a hypoglycaemic agent. Dose dependent glucose uptake assay was performed on L6 myotubes using 2-deoxy-D-[1-(3)H] glucose. Up-regulatory effects of the extracts on the mRNA expression level of Glut-4, PPAR gamma and PI3K have been studied. The association of Momordica charantia with the aqueous and chloroform extracts of Momordica charantia fruit at 6 microg/ml has shown significant up-regulatory effect, respectively, by 3.6-, 2.8- and 3.8-fold on the battery of targets Glut-4, PPAR gamma and PI3K involved in glucose transport. The up-regulation of glucose uptake was comparable with insulin and rosiglitazone which was approximately 2-fold over the control. Moreover, the inhibitory effect of the cyclohexamide on Momordica charantia fruit extract mediated glucose uptake suggested the requirement of new protein synthesis for the enhanced glucose uptake. This study demonstrated the significance of Glut-4, PPAR gamma and PI3K up-regulation by Momordica charantia in augmenting the glucose uptake and homeostasis.

  9. AR DOC: Augmented reality documentaries

    DEFF Research Database (Denmark)

    Vistisen, Peter

    2014-01-01

    Augmented Reality Documentaries (AR DOC) er et ’lille’ Shareplay projekt (ansøgte midler augmented reality cross media løsninger, til at skabe engagerende publikumsformidling...... indenfor oplevelsesindustrien. Projektet har genereret ny viden omkring, hvordan fysisk og digital formidling kan understøttes via Augmented Reality som formidlingsformat....

  10. H2O2 Treatment of HUVECs Facilitates PKC Mediated Thr495 Phosphorylation on eNOS when Pre-treated with High Glucose Levels

    DEFF Research Database (Denmark)

    Guterbaum, Thomas J; Braunstein, Thomas H; Fossum, Anna

    2015-01-01

    Objective: Metabolic syndrome entails hypertension, hyperglycemia, obesity and hypercholesterolemia. This syndrome increases the risk of cardiovascular disease and diabetes. Hyperglycemia during coronary reperfusion is associated with a poor prognosis. Contrastingly, targeting correction of hyper......Objective: Metabolic syndrome entails hypertension, hyperglycemia, obesity and hypercholesterolemia. This syndrome increases the risk of cardiovascular disease and diabetes. Hyperglycemia during coronary reperfusion is associated with a poor prognosis. Contrastingly, targeting correction...... -rich environment. Methods and results: HUVECs (human umbilical vein endothelial cells) were exposed to high glucose (20 mM) for either 20 or 72 hours co-incubated with or without H2 O2 (400 µM) for 30 minutes as models of increased oxidative stress during acute and prolonged hyperglycemia, respectively...... in an increase in Thr495 phosphorylation (to 425%, paffect phosphorylation of Thr495 and Ser1177. Stimulating HUVECs that were pre-incubated with 20 mM glucose for 72 hours with H2 O2...

  11. Oxygen/glucose deprivation induces a reduction in synaptic AMPA receptors on hippocampal CA3 neurons mediated by mGluR1 and adenosine A3 receptors.

    OpenAIRE

    Dennis, Siobhan; Jaafari, Nadia; Cimarosti, Helena; Hanley, Jonathan G.; Henley, Jeremy M.; Mellor, Jack R.

    2011-01-01

    Hippocampal CA1 pyramidal neurons are highly sensitive to ischemic damage, whereas neighboring CA3 pyramidal neurons are less susceptible. It is proposed that switching of AMPA receptor (AMPAR) subunits on CA1 neurons during an in vitro model of ischemia, oxygen/glucose deprivation (OGD), leads to an enhanced permeability of AMPARs to Ca2+, resulting in delayed cell death. However, it is unclear whether the same mechanisms exist in CA3 neurons and whether this underlies the differential sensi...

  12. Oxygen/glucose Deprivation Induces a Reduction in Synaptic AMPA Receptors on Hippocampal CA3 Neurons Mediated by mGluR1 and A3 Receptors

    OpenAIRE

    Dennis, Siobhan H.; Jaafari, Nadia; Cimarosti, Helena; Hanley, Jonathan G.; Henley, Jeremy M.; Mellor, Jack R.

    2011-01-01

    Hippocampal CA1 pyramidal neurons are highly sensitive to ischemic damage, whereas neighbouring CA3 pyramidal neurons are less susceptible. It is proposed that switching of AMPA receptor (AMPAR) subunits on CA1 neurons during an in vitro model of ischemia, oxygen/glucose deprivation (OGD), leads to an enhanced permeability of AMPARs to Ca2+ resulting in delayed cell death. However, it is unclear if the same mechanisms exist in CA3 neurons and whether this underlies the differential sensitivit...

  13. Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model

    OpenAIRE

    Zhang, Huaqiu; Xie, Minjie; Gary P. Schools; Feustel, Paul F.; Wang, Wei; Lei, Ting; Kimelberg, Harold K.; Zhou, Min

    2008-01-01

    Pretreatment of ovarectomized rats with estrogen shows long-term protection via activation of the estrogen receptor (ER). However, it remains unknown whether activation of the ER can provide protection against early neuronal damage when given acutely, we simulated ischemic conditions by applying oxygen and glucose deprived (OGD) solution to acute male rat hippocampal slices and examined the neuronal electrophysiological changes. Pyramidal neurons and interneurons showed a time-dependent membr...

  14. Combining 2-deoxy-D-glucose with fenofibrate leads to tumor cell death mediated by simultaneous induction of energy and ER stress

    OpenAIRE

    Kurtoğlu, Metin; Liu, Huaping; Lucia Leon; Annicchiarico, Clara; Munoz-Pinedo, Cristina; Barredo, Julio; Leclerc, Guy; Merchan, Jaime; Liu, Xiongfei; Lampidis, Theodore J.

    2016-01-01

    Unregulated growth and replication as well as an abnormal microenvironment, leads to elevated levels of stress which is a common trait of cancer. By inducing both energy and endoplasmic reticulum (ER) stress, 2-Deoxy-glucose (2-DG) is particularly well-suited to take advantage of the therapeutic window that heightened stress in tumors provides. Under hypoxia, blocking glycolysis with 2-DG leads to significant lowering of ATP resulting in energy stress and cell death in numerous carcinoma cell...

  15. p16(INK4a suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Li

    Full Text Available Although caloric restriction (CR has been shown to increase lifespan in various animal models, the mechanisms underlying this phenomenon have not yet been revealed. We developed an in vitro system to mimic CR by reducing glucose concentration in cell growth medium which excludes metabolic factors and allows assessment of the effects of CR at the cellular and molecular level. We monitored cellular proliferation of normal WI-38, IMR-90 and MRC-5 human lung fibroblasts and found that glucose restriction (GR can inhibit cellular senescence and significantly extend cellular lifespan compared with cells receiving normal glucose (NG in the culture medium. Moreover, GR decreased expression of p16(INK4a (p16, a well-known senescence-related gene, in all of the tested cell lines. Over-expressed p16 resulted in early replicative senescence in glucose-restricted cells suggesting a crucial role of p16 regulation in GR-induced cellular lifespan extension. The decreased expression of p16 was partly due to GR-induced chromatin remodeling through effects on histone acetylation and methylation of the p16 promoter. GR resulted in an increased expression of SIRT1, a NAD-dependent histone deacetylase, which has positive correlation with CR-induced longevity. The elevated SIRT1 was accompanied by enhanced activation of the Akt/p70S6K1 signaling pathway in response to GR. Furthermore, knockdown of SIRT1 abolished GR-induced p16 repression as well as Akt/p70S6K1 activation implying that SIRT1 may affect p16 repression through direct deacetylation effects and indirect regulation of Akt/p70S6K1 signaling. Collectively, these results provide new insights into interactions between epigenetic and genetic mechanisms on CR-induced longevity that may contribute to anti-aging approaches and also provide a general molecular model for studying CR in vitro in mammalian systems.

  16. Targeted deletion of growth hormone (GH) receptor in macrophage reveals novel osteopontin-mediated effects of GH on glucose homeostasis and insulin sensitivity in diet-induced obesity.

    Science.gov (United States)

    Lu, Chunxia; Kumar, P Anil; Sun, Jinhong; Aggarwal, Anjali; Fan, Yong; Sperling, Mark A; Lumeng, Carey N; Menon, Ram K

    2013-05-31

    We investigated GH action on macrophage (MΦ) by creating a MΦ-specific GH receptor-null mouse model (MacGHR KO). On a normal diet (10% fat), MacGHR KO and littermate controls exhibited similar growth profiles and glucose excursions on intraperitoneal glucose (ipGTT) and insulin tolerance (ITT) tests. However, when challenged with high fat diet (HFD, 45% fat) for 18 weeks, MacGHR KO mice exhibited impaired ipGTT and ITT compared with controls. In MacGHR KO, adipose-tissue (AT) MΦ abundance was increased with skewing toward M1 polarization. Expression of pro-inflammatory cytokines (IL1β, TNF-α, IL6, and osteopontin (OPN)) were increased in MacGHR KO AT stromal vascular fraction (SVF). In MacGHR KO AT, crown-like-structures were increased with decreased insulin-dependent Akt phosphorylation. The abundance of phosphorylated NF-κB and of OPN was increased in SVF and bone-marrow-derived MΦ in MacGHR KO. GH, acting via an NF-κB site in the distal OPN promoter, inhibited the OPN promoter. Thus in diet-induced obesity (DIO), lack of GH action on the MΦ exerts an unexpected deleterious effect on glucose homeostasis by accentuating AT inflammation and NF-κB-dependent activation of OPN expression. These novel results in mice support the possibility that administration of GH could have salutary effects on DIO-associated chronic inflammation and insulin resistance in humans.

  17. A PERITONEAL DIALYSIS REGIMEN LOW IN GLUCOSE AND GLUCOSE DEGRADATION PRODUCTS RESULTS IN INCREASED CANCER ANTIGEN 125 AND PERITONEAL ACTIVATION

    NARCIS (Netherlands)

    le Poole, Caatje Y.; Welten, Angelique G. A.; ter Wee, Piet M.; Paauw, Nanne J.; Djorai, Amina N.; Valentijn, Rob M.; Beelen, Robert H. J.; van den Born, Jacob; van Ittersum, Frans J.

    2012-01-01

    Background: Glucose and glucose degradation products (GDPs) in peritoneal dialysis fluids (PDFs) are both thought to mediate progressive peritoneal worsening. Methods: In a multicenter, prospective, randomized crossover study, incident continuous ambulatory peritoneal dialysis patients were treated

  18. A Direct, Biomass-Based Synthesis of Benzoic Acid: Formic Acid-Mediated Deoxygenation of the Glucose-Derived Materials Quinic Acid and Shikimic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Arceo, Elena; Ellman, Jonathan; Bergman, Robert

    2010-05-03

    An alternative biomass-based route to benzoic acid from the renewable starting materials quinic acid and shikimic acid is described. Benzoic acid is obtained selectively using a highly efficient, one-step formic acid-mediated deoxygenation method.

  19. AMI : Augmented Michelson Interferometer

    OpenAIRE

    Furio, David; Hachet, Martin; Guillet, Jean-Paul; Bousquet, Bruno; Fleck, Stéphanie; Reuter, Patrick; Canioni, Lionel

    2015-01-01

    International audience; Experiments in optics are essential for learning and understanding physical phenomena. The problem with these experiments is that they are generally time consuming for both their construction and their maintenance, potentially dangerous through the use of laser sources, and often expensive due to high technology optical components.We propose to simulate such experiments by way of hybrid systems that exploit both spatial augmented reality and tangible interaction. In pa...

  20. Augmented Reality als Bildungsenhancement?

    OpenAIRE

    Damberger, Thomas

    2015-01-01

    Die Realität, die sich mithilfe von Datenbrillen und Smartphone Applikationen in die virtuelle Welt hinein ausdehnt, erfährt eine Form des Enhancements. Ein solches Enhancement kann unter bestimmten Voraussetzungen als Bildungsenhancement verstanden werden. Der Text befasst sich mit Formen der erweiterten Realität, ferner mit dem, um was es wesentlich bei der Bildung geht und zuletzt mit den Bedingungen, die erforderlich sind, um diesem Wesentlichen mit Hilfe von augmented reality besser zum ...

  1. AUGMENTED REALITY BASED ASSISTANCE

    Directory of Open Access Journals (Sweden)

    N.R.Raajan

    2013-04-01

    Full Text Available The concept of Augmented Reality can be explained as a superimposition of computer generated two dimensional or three dimensional objects over the real time scene acquired into thecapturing device. Thus Augmented Reality adds additional information to the real scene and this can be implemented with the help of markers. The development of the application is simple and easier in case of AR. This idea is extended to the development of Augmented Reality based book that act as a tour guide. This travel guide can give all the basic information regarding the necessities of a finer travel around the places of the destinations. The application will detect the markers found in the real scene and superimpose them with multimedia data giving enormous information. The application can also be made to redirect to the web links for easy access of certain other utilities by interaction. The same idea can also be utilized in engineering laboratories to understand the working of the circuit by visualizing the working of the same circuit where the diagram itself can be used as a marker and thus enhancing the self learning among the students.

  2. Integrated sensor-augmented pump therapy systems [the MiniMed® Paradigm™ Veo system and the Vibe™ and G4® PLATINUM CGM (continuous glucose monitoring) system] for managing blood glucose levels in type 1 diabetes: a systematic review and economic evaluation.

    Science.gov (United States)

    Riemsma, Rob; Corro Ramos, Isaac; Birnie, Richard; Büyükkaramikli, Nasuh; Armstrong, Nigel; Ryder, Steve; Duffy, Steven; Worthy, Gill; Al, Maiwenn; Severens, Johan; Kleijnen, Jos

    2016-02-01

    In recent years, meters for continuous monitoring of interstitial fluid glucose have been introduced to help people with type 1 diabetes mellitus (T1DM) to achieve better control of their disease. The objective of this project was to summarise the evidence on the clinical effectiveness and cost-effectiveness of the MiniMed(®) Paradigm™ Veo system (Medtronic Inc., Northridge, CA, USA) and the Vibe™ (Animas(®) Corporation, West Chester, PA, USA) and G4(®) PLATINUM CGM (continuous glucose monitoring) system (Dexcom Inc., San Diego, CA, USA) in comparison with multiple daily insulin injections (MDIs) or continuous subcutaneous insulin infusion (CSII), both with either self-monitoring of blood glucose (SMBG) or CGM, for the management of T1DM in adults and children. A systematic review was conducted in accordance with the principles of the Centre for Reviews and Dissemination guidance and the National Institute for Health and Care Excellence Diagnostic Assessment Programme manual. We searched 14 databases, three trial registries and two conference proceedings from study inception up to September 2014. In addition, reference lists of relevant systematic reviews were checked. In the absence of randomised controlled trials directly comparing Veo or an integrated CSII + CGM system, such as Vibe, with comparator interventions, indirect treatment comparisons were performed if possible. A commercially available cost-effectiveness model, the IMS Centre for Outcomes Research and Effectiveness diabetes model version 8.5 (IMS Health, Danbury, CT, USA), was used for this assessment. This model is an internet-based, interactive simulation model that predicts the long-term health outcomes and costs associated with the management of T1DM and type 2 diabetes. The model consists of 15 submodels designed to simulate diabetes-related complications, non-specific mortality and costs over time. As the model simulates individual patients over time, it updates risk factors and

  3. In Vivo Zinc Finger Nuclease-mediated Targeted Integration of a Glucose-6-phosphatase Transgene Promotes Survival in Mice With Glycogen Storage Disease Type IA.

    Science.gov (United States)

    Landau, Dustin J; Brooks, Elizabeth Drake; Perez-Pinera, Pablo; Amarasekara, Hiruni; Mefferd, Adam; Li, Songtao; Bird, Andrew; Gersbach, Charles A; Koeberl, Dwight D

    2016-04-01

    Glycogen storage disease type Ia (GSD Ia) is caused by glucose-6-phosphatase (G6Pase) deficiency in association with severe, life-threatening hypoglycemia that necessitates lifelong dietary therapy. Here we show that use of a zinc-finger nuclease (ZFN) targeted to the ROSA26 safe harbor locus and a ROSA26-targeting vector containing a G6PC donor transgene, both delivered with adeno-associated virus (AAV) vectors, markedly improved survival of G6Pase knockout (G6Pase-KO) mice compared with mice receiving the donor vector alone (P Ia, as compared with normal littermates, at 8 months following vector administration (P Ia.

  4. Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Das, Joydeep; Vasan, Vandana; Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in

    2012-01-15

    Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120 mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markers and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NFκB in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NFκB translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Highlights: ► Taurine controls blood glucose via protection of pancreatic β cells in diabetic rat. ► Taurine controls blood glucose via increasing the insulin level in diabetic rat. ► Taurine improves cardiac AKT/GLUT4 signaling

  5. Pinitol Supplementation Does Not Affect Insulin-Mediated Glucose Metabolism and Muscle Insulin Receptor Content and Phosphorylation in Older Humans12

    OpenAIRE

    Campbell, Wayne W.; Haub, Mark D.; Fluckey, James D.; Ostlund, Richard E.; Thyfault, John P.; Morse-Carrithers, Hannah; Hulver, Matthew W.; Birge, Zonda K.

    2004-01-01

    This study assessed the effect of oral pinitol supplementation on oral and intravenous glucose tolerances and on skeletal muscle insulin receptor content and phosphorylation in older people. Fifteen people (6 men, 9 women; age 66 ± 8 y; BMI 27.9 ± 3.3 kg/m2; hemoglobin A1c 5.39 ± 0.46%, mean ± SD) completed a 7-wk protocol. Subjects were randomly assigned to groups that during wk 2−7 consumed twice daily either a non-nutritive beverage (Placebo group, n = 8) or the same beverage with 1000 mg ...

  6. DANGER is involved in high glucose-induced radioresistance through inhibiting DAPK-mediated anoikis in non-small cell lung cancer.

    Science.gov (United States)

    Kwon, TaeWoo; Youn, HyeSook; Son, Beomseok; Kim, Daehoon; Seong, Ki Moon; Park, Sungkyun; Kim, Wanyeon; Youn, BuHyun

    2016-02-09

    18F-labeled fluorodeoxyglucose (FDG) uptake during FDG positron emission tomography seems to reflect increased radioresistance. However, the exact molecular mechanism underlying high glucose (HG)-induced radioresistance is unclear. In the current study, we showed that ionizing radiation-induced activation of the MEK-ERK-DAPK-p53 signaling axis is required for anoikis (anchorage-dependent apoptosis) of non-small cell lung cancer (NSCLC) cells in normal glucose media. Phosphorylation of DAPK at Ser734 by ERK was essential for p53 transcriptional activity and radiosensitization. In HG media, overexpressed DANGER directly bound to the death domain of DAPK, thus inhibiting the catalytic activity of DAPK. In addition, inhibition of the DAPK-p53 signaling axis by DANGER promoted anoikis-resistance and epithelial-mesenchymal transition (EMT), resulting in radioresistance of HG-treated NSCLC cells. Notably, knockdown of DANGER enhanced anoikis, EMT inhibition, and radiosensitization in a mouse xenograft model of lung cancer. Taken together, our findings offered evidence that overexpression of DANGER and the subsequent inhibitory effect on DAPK kinase activity are critical responses that account for HG-induced radioresistance of NSCLC.

  7. IL-6 induces lipolysis and mitochondrial dysfunction, but does not affect insulin-mediated glucose transport in 3T3-L1 adipocytes.

    Science.gov (United States)

    Ji, Chenbo; Chen, Xiaohui; Gao, Chunlin; Jiao, Liuhong; Wang, Jianguo; Xu, Guangfeng; Fu, Hailong; Guo, Xirong; Zhao, Yaping

    2011-08-01

    Interleukin-6 (IL-6) has emerged as an important cytokine involved in the regulation of metabolism. However, the role of IL-6 in the etiology of obesity and insulin resistance is not fully understood. Mitochondria are key organelles of energy metabolism, and there is growing evidence that mitochondrial dysfunction plays a crucial role in the pathogenesis of obesity-associated insulin resistance. In this study, we determined the direct effect of IL-6 on lipolysis in adipocytes, and the effects of IL-6 on mitochondrial function were investigated. We found that cells treated with IL-6 displayed fewer lipids and an elevated glycerol release rate. Further, IL-6 treatment led to decreased mitochondrial membrane potential, decreased cellular ATP production, and increased intracellular ROS levels. The mitochondria in IL-6-treated cells became swollen and hollow with reduced or missing cristae. However, insulin-stimulated glucose transport was unaltered. PGC-1α, NRF1, and mtTFA mRNA levels were markedly increased, and the mitochondrial contents were also increased. Our results demonstrate that IL-6 can exert a direct lipolytic effect and induce mitochondrial dysfunction. However, IL-6 did not affect insulin sensitivity in adipocytes in vitro. We deduce that in these cells, enhanced mitochondrial biogenesis might play a compensatory role in glucose transport.

  8. Fisetin Suppresses Lipid Accumulation in Mouse Adipocytic 3T3-L1 Cells by Repressing GLUT4-Mediated Glucose Uptake through Inhibition of mTOR-C/EBPα Signaling.

    Science.gov (United States)

    Watanabe, Marina; Hisatake, Mitsuhiro; Fujimori, Ko

    2015-05-27

    3,7,3',4'-Tetrahydroxyflavone (fisetin) is a flavonoid found in vegetables and fruits having broad biological activities. Here the effects of fisetin on adipogenesis and its regulatory mechanism in mouse adipocytic 3T3-L1 cells are studied. Fisetin inhibited the accumulation of intracellular lipids and lowered the expression of adipogenic genes such as peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein (C/EBP) α and fatty acid-binding protein 4 (aP2) during adipogenesis. Moreover, the mRNA levels of genes such as acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase involved in the fatty acid biosynthesis (lipogenesis) were reduced by the treatment with fisetin. The expression level of the glucose transporter 4 (GLUT4) gene was also decreased by fisetin, resulting in down-regulation of glucose uptake. Furthermore, fisetin inhibited the phosphorylation of the mammalian target of rapamycin (mTOR) and that of p70 ribosomal S6 kinase, a target of the mTOR complex, the inhibition of which was followed by a decreased mRNA level of the C/EBPα gene. The results obtained from a chromatin immunoprecipitation assay demonstrated that the ability of C/EBPα to bind to the GLUT4 gene promoter was reduced by the treatment with fisetin, which agreed well with those obtained when 3T3-L1 cells were allowed to differentiate into adipocytes in medium in the presence of rapamycin, an inhibitor for mTOR. These results indicate that fisetin suppressed the accumulation of intracellular lipids by inhibiting GLUT4-mediated glucose uptake through inhibition of the mTOR-C/EBPα signaling in 3T3-L1 cells.

  9. Carbon nanotubes-ionic liquid nanocomposites sensing platform for NADH oxidation and oxygen, glucose detection in blood.

    Science.gov (United States)

    Bai, Lu; Wen, Dan; Yin, Jianyuan; Deng, Liu; Zhu, Chengzhou; Dong, Shaojun

    2012-03-15

    An excellent electrochemical sensing platform has been designed by combining the huge specific surface area of carbon nanotubes (CNTs) and the remarkable conductivity of ionic liquid (IL). IL can easily untangle CNTs bundles and disperse CNTs by itself under grinding condition due to the π-π interaction between CNTs and IL. The resulting nanocomposites showed an augmentation on the voltammetric and amperometric behaviors of electrocatalytic activity toward O(2) and NADH. Therefore, such an efficient platform was developed to fabricate mediator-free oxygen sensor and glucose biosensor based on glucose dehydrogenase (GDH). O(2) could be determined in the range of zero to one hundred percent of O(2) content with the detection limit of 126 μg L(-1) (S/N=3). The glucose biosensor which was constructed by entrapping GDH into chitosan on the nanocomposites modified glassy carbon electrode surface, exhibited good electrocatalytic oxidation toward glucose with a detection limit of 9 μM in the linear range of 0.02-1mM. We also applied the as-prepared sensors to detect oxygen and glucose in real blood samples and acquired satisfied results. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Mutually Augmented Cognition

    Science.gov (United States)

    Friesdorf, Florian; Pangercic, Dejan; Bubb, Heiner; Beetz, Michael

    In mac, an ergonomic dialog-system and algorithms will be developed that enable human experts and companions to be integrated into knowledge gathering and decision making processes of highly complex cognitive systems (e.g. Assistive Household as manifested further in the paper). In this event we propose to join algorithms and methodologies coming from Ergonomics and Artificial Intelligence that: a) make cognitive systems more congenial for non-expert humans, b) facilitate their comprehension by utilizing a high-level expandable control code for human experts and c) augment representation of such cognitive system into “deep representation” obtained through an interaction with human companions.

  11. Radiative Augmented Combustion.

    Science.gov (United States)

    1985-08-12

    86-0085 In 00I to RADIATIVE AUGMENTED COMBUSTION MOSHE LAVID M.L. ENERGIA , INC. P.O. BOX 1468 1 PRINCETON, NEW JERSEY 08542 AUGUST 1985 *.. plo...Combustion conducted at M.L. ENERGIA . It is funded by the Air Force Office of Scientific Research under Contract No. F49620-83-C-0133, with Dr. J.M...reported. It covers the second year of the contract, from July 15, 1984 through July 14, 1985. The work was performed at ENERGIA , Princeton, New Jersey

  12. Augmented Reality Oculus Rift

    OpenAIRE

    Höll, Markus; Heran, Nikolaus; Lepetit, Vincent

    2016-01-01

    This paper covers the whole process of developing an Augmented Reality Stereoscopig Render Engine for the Oculus Rift. To capture the real world in form of a camera stream, two cameras with fish-eye lenses had to be installed on the Oculus Rift DK1 hardware. The idea was inspired by Steptoe \\cite{steptoe2014presence}. After the introduction, a theoretical part covers all the most neccessary elements to achieve an AR System for the Oculus Rift, following the implementation part where the code ...

  13. Regulation of insulin-stimulated glucose uptake in rat white adipose tissue upon chronic central leptin infusion: effects on adiposity.

    Science.gov (United States)

    Bonzón-Kulichenko, Elena; Fernández-Agulló, Teresa; Moltó, Eduardo; Serrano, Rosario; Fernández, Alejandro; Ros, Manuel; Carrascosa, José M; Arribas, Carmen; Martínez, Carmen; Andrés, Antonio; Gallardo, Nilda

    2011-04-01

    Leptin enhances the glucose utilization in most insulin target tissues and paradoxically decreases it in white adipose tissue (WAT), but knowledge of the mechanisms underlying the inhibitory effect of central leptin on the insulin-dependent glucose uptake in WAT is limited. After 7 d intracerebroventricular leptin treatment (0.2 μg/d) of rats, the overall insulin sensitivity and the responsiveness of WAT after acute in vivo insulin administration were analyzed. We also performed unilateral WAT denervation to clarify the role of the autonomic nervous system in leptin effects on the insulin-stimulated [(3)H]-2-deoxyglucose transport in WAT. Central leptin improved the overall insulin sensitivity but decreased the in vivo insulin action in WAT, including insulin receptor autophosphorylation, insulin receptor substrate-1 tyrosine-phosphorylation, and Akt activation. In this tissue, insulin receptor substrate-1 and glucose transporter 4 mRNA and protein levels were down-regulated after central leptin treatment. Additionally, a remarkable up-regulation of resistin, together with an augmented expression of suppressor of cytokine signaling 3 in WAT, was also observed in leptin-treated rats. As a result, the insulin-stimulated glucose transporter 4 insertion at the plasma membrane and the glucose uptake in WAT were impaired in leptin-treated rats. Finally, denervation of WAT abolished the inhibitory effect of central leptin on glucose transport and decreased suppressor of cytokine signaling 3 and resistin levels in this tissue, suggesting that resistin, in an autocrine/paracrine manner, might be a mediator of central leptin antagonism of insulin action in WAT. We conclude that central leptin, inhibiting the insulin-stimulated glucose uptake in WAT, may regulate glucose availability for triacylglyceride formation and accumulation in this tissue, thereby contributing to the control of adiposity.

  14. AMP-activated protein kinase-dependent autophagy mediated the protective effect of sonic hedgehog pathway on oxygen glucose deprivation-induced injury of cardiomyocytes.

    Science.gov (United States)

    Xiao, Qing; Yang, Ya; Qin, Yuan; He, Yan-Hua; Chen, Kui-Xiang; Zhu, Jian-Wei; Zhang, Gui-Ping; Luo, Jian-Dong

    2015-02-13

    Sonic hedgehog (Shh) pathway has been reported to protect cardiomyocytes in myocardial infarction (MI), but the underlying mechanism is not clear. Here, we provide evidence that Shh pathway induces cardiomyocytes survival through AMP-activated protein kinase-dependent autophagy. Shh pathway agonist SAG increased the expression of LC3-II, and induced the formation of autophagosomes in cultured H9c2 cardiomyocytes under oxygen glucose deprivation (OGD) 1 h and 4 h. Moreover, SAG induced a profound AMP-activated protein kinase (AMPK) activation, and then directly phosphorylated and activated the downstream autophagy initiator Ulk1, independent of the autophagy suppressor mammalian target of rapamycin (mTOR) complex 1. Taken together, our results have shown that Shh activates AMPK-dependent autophagy in cardiomyocytes under OGD, suggesting a role of autophagy in Shh-induced cellular protection.

  15. Tc(V)-DMS tumor localization mechanism: a pH-sensitive Tc(V)-DMS-enhanced target/nontarget ratio by glucose-mediated acidosis

    Energy Technology Data Exchange (ETDEWEB)

    Horiuchi, Kazuko E-mail: shkazuko@pharm.kyoto-u.ac.jp; Saji, Hideo; Yokoyama, Akira

    1998-08-01

    Since the conception of the pentavalent technetium polynuclear complex of dimercaptosuccinic acid, Tc(V)-DMS, a great number of papers published on its clinical applicability forced us to question ''how tumor tissue appropriates the Tc(V)-DMS.'' Preliminary in vitro studies with Ehrlich ascites tumor cells (EATC) indicated the pH-sensitive character of this tumor agent. From this finding and the well-established notion that malignant tumors are more acidic than normal tissue, the in vivo correlation of Tc(V)-DMS accumulation in tumor tissue with its tissue acidification was considered of interest. The systemic lowering of tumor tissue pH by the stimulation of aerobic glycolysis has been well reported. In the present paper, the response of Tc(V)-DMS tumor accumulation to acidification induced by the glucose administration was explored in EATC-bearing mice. Measurement of tumor tissue pH was carried out by direct microelectrode technique and by histochemical umbelliferone technique in tumor tissue excised from EATC bearing mice. The regional acidity distribution is correlated with the regional radioactivity distribution registered by autoradiography. Evidence related to the pH sensitiveness of Tc(V)-DMS in response to glycolytic acidification was gathered; the pH measurement and the in vivo biodistribution of the double-tracer macroautoradiography with C-14 deoxyglucose (C-14-DG) demonstrated that the regional tissue distribution of Tc(V)-DMS was superimposed to that of C-14-DG. The glucose interventional modality offers the premier foundation for the interpretation of Tc(V)-DMS accumulation in diagnostic studies of malignant tumors.

  16. Augmented Reality for Science Education

    DEFF Research Database (Denmark)

    Brandt, Harald; Nielsen, Birgitte Lund; Georgsen, Marianne

    2015-01-01

    Augmented reality (AR) holds great promise as a learning tool. So far, however, most research has looked at the technology itself – and AR has been used primarily for commercial purposes. As a learning tool, AR supports an inquiry-based approach to science education with a high level of student...... involvement. The AR-sci-project (Augmented Reality for SCIence education) addresses the issue of applying augmented reality in developing innovative science education and enhancing the quality of science teaching and learning....

  17. Augmented Reality for Science Education

    DEFF Research Database (Denmark)

    Brandt, Harald; Nielsen, Birgitte Lund; Georgsen, Marianne

    Augmented reality (AR) holds great promise as a learning tool. So far, however, most research has looked at the technology itself – and AR has been used primarily for commercial purposes. As a learning tool, AR supports an inquiry-based approach to science education with a high level of student...... involvement. The AR-sci-project (Augmented Reality for SCIence education) addresses the issue of applying augmented reality in developing innovative science education and enhancing the quality of science teaching and learning....

  18. [Intracellular signals involved in glucose control].

    Science.gov (United States)

    Cruz, M; Velasco, E; Kumate, J

    2001-01-01

    Many proteins are involved in glucose control. The first step for glucose uptake is insulin receptor-binding. Stimulation of the insulin receptor results in rapid autophosphorylation and conformational changes in the beta chain and the subsequent phosphorylation of the insulin receptor substrate. This results in the docking of several SH2 domain proteins, including PI 3-kinase and other adapters. The final event is glucose transporter (GLUT) translocation to the cell surface. GLUT is in the cytosol but after insulin stimulation, several proteins are activated either in the GLUT vesicles or in the inner membrane. The role of the cytoskeleton is not well known, but it apparently participates in membrane fusion and vesicle mobilization. After glucose uptake, several hexokines metabolize the glucose to generate energy, convert the glucose in glycogen and store it. Type 2 diabetes is characterized by high glucose levels and insulin resistance. The insulin receptor is diminished on the cell surface membrane, tyrosine phosphorylation is decreased, serine and threonine phosphorylation is augmented. Apparently, the main problem with GLUT protein is in its translocation to the cell surface. At present, we know the role of many proteins involved in glucose control. However, we do not understand the significance of insulin resistance at the molecular level with type 2 diabetes.

  19. Augmented reality in medical education?

    National Research Council Canada - National Science Library

    Kamphuis, Carolien; Barsom, Esther; Schijven, Marlies; Christoph, Noor

    2014-01-01

    .... Educational technology and more specifically augmented reality (AR) has the potential to offer a highly realistic situated learning experience supportive of complex medical learning and transfer...

  20. Transcriptional coactivator p300 regulates glucose-induced gene expression in endothelial cells.

    Science.gov (United States)

    Chen, Shali; Feng, Biao; George, Biju; Chakrabarti, Rana; Chen, Megan; Chakrabarti, Subrata

    2010-01-01

    Sustained hyperglycemia in diabetes causes alteration of a large number of transcription factors and mRNA transcripts, leading to tissue damage. We investigated whether p300, a transcriptional coactivator with histone acetyl transferase activity, regulates glucose-induced activation of transcription factors and subsequent upregulation of vasoactive factors and extracellular matrix (ECM) proteins in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated in varied glucose concentrations and were studied after p300 small interfering RNA (siRNA) transfection, p300 overexpression, or incubation with the p300 inhibitor curcumin. Histone H2AX phosphorylation and lysine acetylation were examined for oxidative DNA damage and p300 activation. Screening for transcription factors was performed with the Luminex system. Alterations of selected transcription factors were validated. mRNA expression of p300, endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and fibronectin (FN) and its splice variant EDB(+)FN and FN protein production were analyzed. HUVECs in 25 mmol/l glucose showed increased p300 production accompanied by increased binding of p300 to ET-1 and FN promoters, augmented histone acetylation, H2AX phosphorylation, activation of multiple transcription factors, and increased mRNA expression of vasoactive factors and ECM proteins. p300 overexpression showed a glucose-like effect on the mRNA expression of ET-1, VEGF, and FN. Furthermore, siRNA-mediated p300 blockade or chemical inhibitor of p300 prevented such glucose-induced changes. Similar mRNA upregulation was also seen in the organ culture of vascular tissues, which was prevented by p300 siRNA transfection. Data from these studies suggest that glucose-induced p300 upregulation is an important upstream epigenetic mechanism regulating gene expression of vasoactive factors and ECM proteins in endothelial cells and is a potential therapeutic target for diabetic complications.

  1. Mediator-free interaction of glucose oxidase, as model enzyme for immobilization, with Al-doped and undoped ZnO thin films laser-deposited on polycarbonate supports.

    Science.gov (United States)

    V T K P, Fidal; Inguva, Saikumar; Krishnamurthy, Satheesh; Marsili, Enrico; Mosnier, Jean-Paul; T S, Chandra

    2017-01-01

    Al doped and undoped ZnO thin films were deposited by pulsed-laser deposition on polycarbonate sheets. The films were characterized by optical transmission, Hall effect measurement, XRD and SEM. Optical transmission and surface reflectometry studies showed good transparency with thicknesses ∼100nm and surface roughness of 10nm. Hall effect measurements showed that the sheet carrier concentration was -1.44×10(15)cm(-2) for AZO and -6×10(14)cm(-2) for ZnO. The films were then modified by drop-casting glucose oxidase (GOx) without the use of any mediators. Higher protein concentration was observed on ZnO as compared to AZO with higher specific activity for ZnO (0.042Umg(-1)) compared to AZO (0.032Umg(-1)), and was in agreement with cyclic voltemmetry (CV). X-ray photoelectron spectroscopy (XPS) suggested that the protein was bound by dipole interactions between AZO lattice oxygen and the amino group of the enzyme. Chronoamperometry showed sensitivity of 5.5μAmM(-1)cm(-2) towards glucose for GOx/AZO and 2.2μAmM(-1)cm(-2) for GOx/ZnO. The limit of detection (LoD) was 167μM of glucose for GOx/AZO, as compared to 360μM for GOx/ZnO. The linearity was 0.28-28mM for GOx/AZO whereas it was 0.6-28mM for GOx/ZnO with a response time of 10s. Possibly due to higher enzyme loading, the decrease of impedance in presence of glucose was larger for GOx/ZnO as compared to GOx/AZO in electrochemical impedance spectroscopy (EIS). Analyses with clinical blood serum samples showed that the systems had good reproducibility and accuracy. The characteristics of novel ZnO and AZO thin films with GOx as a model enzyme, should prove useful for the future fabrication of inexpensive, highly sensitive, disposable electrochemical biosensors for high throughput diagnostics.

  2. The effect of endurance training and subsequent physical inactivity on glycaemic control after oral glucose load and physical exercise in healthy men

    Science.gov (United States)

    Radikova, Zofia; Ksinantova, Lucia; Kaciuba-Uscilko, Hanna; Nazar, Krystyna; Vigas, Milan; Koska, Juraj

    2007-02-01

    Physical inactivity during space flight has a profound effect on glucose metabolism. The aim of this study was to test whether endurance training (ET) may improve a negative effect of subsequent -6∘ head-down bed rest (HDBR) on glucose metabolism. Fourteen healthy males completed the study consisting of 6 weeks lasting ET followed by 6 days HDBR. Treadmill exercise at 80% of pre-training VO2max and 75 g oral glucose tolerance test (OGTT) were performed before and after ET as well as after HDBR. ET increased VO2max by 11%. ET significantly lowered while HDBR had no effect on fasting and OGTT plasma glucose levels. ET had no effect while HDBR was followed by an augmentation of insulin and C-peptide response to OGTT. Insulin sensitivity tended to increase after ET and to decrease during HDBR, however, mostly without statistical significance. Plasma glucose, insulin and C-peptide response to exercise were elevated after HDBR only. Our study shows that antecedent physical training could ameliorate a negative effect of simulated microgravity on insulin-mediated glucose metabolism.

  3. Augmented reality system

    Science.gov (United States)

    Lin, Chien-Liang; Su, Yu-Zheng; Hung, Min-Wei; Huang, Kuo-Cheng

    2010-08-01

    In recent years, Augmented Reality (AR)[1][2][3] is very popular in universities and research organizations. The AR technology has been widely used in Virtual Reality (VR) fields, such as sophisticated weapons, flight vehicle development, data model visualization, virtual training, entertainment and arts. AR has characteristics to enhance the display output as a real environment with specific user interactive functions or specific object recognitions. It can be use in medical treatment, anatomy training, precision instrument casting, warplane guidance, engineering and distance robot control. AR has a lot of vantages than VR. This system developed combines sensors, software and imaging algorithms to make users feel real, actual and existing. Imaging algorithms include gray level method, image binarization method, and white balance method in order to make accurate image recognition and overcome the effects of light.

  4. Pure laparoscopic augmentation ileocystoplasty.

    Science.gov (United States)

    Rebouças, Rafael B; Monteiro, Rodrigo C; Souza, Thiago N S de; Aragão, Augusto J de; Burity, Camila R T; Nóbrega, Júlio C de A; Oliveira, Natália S C de; Abrantes, Ramon B; Dantas Júnior, Luiz B; Cartaxo Filho, Ricardo; Negromonte, Gustavo R P; Sampaio, Rafael da C R; Britto, Cesar A

    2014-01-01

    Guillain-Barre syndrome is an acute neuropathy that rarely compromises bladder function. Conservative management including clean intermittent catheterization and pharmacotherapy is the primary approach for hypocompliant contracted bladder. Surgical treatment may be used in refractory cases to improve bladder compliance and capacity in order to protect the upper urinary tract. We describe a case of pure laparoscopic augmentation ileocystoplasty in a patient affected by Guillain-Barre syndrome. A 15-year-old female, complaining of voiding dysfunction, recurrent urinary tract infection and worsening renal function for three months. A previous history of Guillain-Barre syndrome on childhood was related. A voiding cystourethrography showed a pine-cone bladder with moderate post-void residual urine. The urodynamic demonstrated a hypocompliant bladder and small bladder capacity (190 mL) with high detrusor pressure (54 cmH2O). Nonsurgical treatments were attempted, however unsuccessfully.

  5. NAESA Augmentation Pilot Project

    Science.gov (United States)

    Hoover, John J.

    1998-01-01

    This project was one project within the Native American Earth and Space Academy (NAESA). NAESA is a national initiative comprised of several organizations that support programs which focus on 1) enhancing the technological, scientific and pedagogical skills of K-14 teachers who instruct Native Americans, 2) enhancing the understanding and applications of science, technology, and engineering of college-bound Native Americans and teaching them general college "survival skills" (e.g., test taking, time management, study habits), 3) enhancing the scientific and pedagogical skills of the faculty of tribally-controllcd colleges and community colleges with large Native American enrollments, and 4) strengthening the critical relationships between students, their parents, tribal elders, and their communities. This Augmentation Pilot Project focused on the areas of community-school alliances and intemet technology use in teaching and learning and daily living addressing five major objectives.

  6. Magnetohydrodynamic Augmented Propulsion Experiment

    Science.gov (United States)

    Litchford, Ron J.

    2008-01-01

    Over the past several years, efforts have been under way to design and develop an operationally flexible research facility for investigating the use of cross-field MHD accelerators as a potential thrust augmentation device for thermal propulsion systems. The baseline configuration for this high-power experimental facility utilizes a 1.5-MWe multi-gas arc-heater as a thermal driver for a 2-MWe MHD accelerator, which resides in a large-bore 2-tesla electromagnet. A preliminary design study using NaK seeded nitrogen as the working fluid led to an externally diagonalized segmented MHD channel configuration based on an expendable heat-sink design concept. The current status report includes a review of engineering/design work and performance optimization analyses and summarizes component hardware fabrication and development efforts, preliminary testing results, and recent progress toward full-up assembly and testing

  7. Augmented Virtual Reality Laboratory

    Science.gov (United States)

    Tully-Hanson, Benjamin

    2015-01-01

    Real time motion tracking hardware has for the most part been cost prohibitive for research to regularly take place until recently. With the release of the Microsoft Kinect in November 2010, researchers now have access to a device that for a few hundred dollars is capable of providing redgreenblue (RGB), depth, and skeleton data. It is also capable of tracking multiple people in real time. For its original intended purposes, i.e. gaming, being used with the Xbox 360 and eventually Xbox One, it performs quite well. However, researchers soon found that although the sensor is versatile, it has limitations in real world applications. I was brought aboard this summer by William Little in the Augmented Virtual Reality (AVR) Lab at Kennedy Space Center to find solutions to these limitations.

  8. Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury.

    Science.gov (United States)

    Gao, Xiao-Ya; Huang, Jian-Ou; Hu, Ya-Fang; Gu, Yong; Zhu, Shu-Zhen; Huang, Kai-Bin; Chen, Jin-Yu; Pan, Su-Yue

    2014-11-18

    Co-treatment of neuroprotective reagents may improve the therapeutic efficacy of hypothermia in protecting neurons during ischemic stroke. This study aimed to find promising drugs that enhance the neuroprotective effect of mild hypothermia (MH). 26 candidate drugs were selected based on different targets. Primary cultured cortical neurons were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) to induce neuronal damage, followed by either single treatment (a drug or MH) or a combination of a drug and MH. Results showed that, compared with single treatment, combination of MH with brain derived neurotrophic factor, glibenclamide, dizocilpine, human urinary kallidinogenase or neuroglobin displayed higher proportion of neuronal cell viability. The latter three drugs also caused less apoptosis rate in combined treatment. Furthermore, co-treatment of those three drugs and MH decreased the level of reactive oxygen species (ROS) and intracellular calcium accumulation, as well as stabilized mitochondrial membrane potential (MMP), indicating the combined neuroprotective effects are probably via inhibiting mitochondrial apoptosis pathway. Taken together, the study suggests that combined treatment with hypothermia and certain neuroprotective reagents provide a better protection against OGD/R-induced neuronal injury.

  9. GOLPH3 Mediated Golgi Stress Response in Modulating N2A Cell Death upon Oxygen-Glucose Deprivation and Reoxygenation Injury.

    Science.gov (United States)

    Li, Ting; You, Hong; Mo, Xiaoye; He, Wenfang; Tang, Xiangqi; Jiang, Zheng; Chen, Shiyu; Chen, Yang; Zhang, Jie; Hu, Zhiping

    2016-03-01

    Increasing evidence implicating that the organelle-dependent initiation of cell death merits further research. The evidence also implicates Golgi as a sensor and common downstream-effector of stress signals in cell death pathways, and it undergoes disassembly and fragmentation during apoptosis in several neurological disorders. It has also been reported that during apoptotic cell death, there is a cross talk between ER, mitochondria, and Golgi. Thus, we hypothesized that Golgi might trigger death signals during oxidative stress through its own machinery. The current study found that GOLPH3, an outer membrane protein of the Golgi complex, was significantly upregulated in N2A cells upon oxygen-glucose deprivation and reoxygenation (OGD/R), positioning from the compact perinuclear ribbon to dispersed vesicle-like structures throughout the cytoplasm. Additionally, elevated GOLPH3 promoted a stress-induced conversion of the LC3 subunit I to II and reactive oxygen species (ROS) production in long-term OGD/R groups. The collective data indicated that GOLPH3 not only acted as a sensor of Golgi stress for its prompt upregulation during oxidative stress but also as an initiator that triggered and propagated specific Golgi stress signals to downstream effectors. This affected ROS production and stress-related autophagy and finally controlled the entry into apoptosis. The data also supported the hypothesis that the Golgi apparatus could be an ideal target for stroke, neurodegenerative diseases, or cancer therapy through its own functional proteins.

  10. Microbially-mediated Destabilization Of Sedimentary Organic Carbon: Isotopic Tracking of Carbon Movement in Laboratory Incubations of Glucose-amended Aquifer Sediment to Determine Priming Effects

    Science.gov (United States)

    Pracht, L. E.; Polizzotto, M.; Neumann, R. B.

    2016-12-01

    Arsenic-contaminated groundwater is a worldwide concern; the result of both geogenic and anthropogenic sources. In naturally-contaminated systems, organic carbon fueling reductive dissolution is considered to be the primary mechanism of mobilization of arsenic off sediment into groundwater. Previous laboratory incubations of aquifer sediment and groundwater collected from a contaminated subsurface system in Bangladesh revealed a pool of biologically available organic carbon mobilized from the sandy sediment. Results indicated that sediments can contain chemically labile organic carbon that is physically protected or otherwise inaccessible to microbial communities. Disturbance of the aquifer matrix could destabilize this pool of sedimentary organic carbon and fuel microbial reactions that mobilize contaminants such as arsenic. Here we present results from laboratory incubations conducted to test the "priming" hypothesis, that an influx of bioavailable surface-derived organic carbon can fuel microbial reactions that target the solid phase and destabilize sedimentary organic carbon, fueling further reactions. Waters containing a range of glucose concentrations were mixed with sediment collected from a Cambodian aquifer, and concentrations and isotopic signatures of carbon were tracked over time in each material phase. The aquifer sediment contained arsenic-bearing oxide minerals, and thus, dissolved concentrations of arsenic, iron, and manganese concentrations were also measured. Results conceptually demonstrate how both surface and sedimentary derived organic carbon can interact to fuel microbial reactions that mobilize arsenic and impact groundwater quality.

  11. Analysis of BH3-only proteins upregulated in response to oxygen/glucose deprivation in cortical neurons identifies Bmf but not Noxa as potential mediator of neuronal injury.

    Science.gov (United States)

    Pfeiffer, S; Anilkumar, U; Chen, G; Ramírez-Peinado, S; Galindo-Moreno, J; Muñoz-Pinedo, C; Prehn, J H M

    2014-10-09

    Stress signaling in response to oxygen/glucose deprivation (OGD) and ischemic injury activates a group of pro-apoptotic genes, the Bcl-2 homology domain 3 (BH3)-only proteins, which are capable of activating the mitochondrial apoptosis pathway. Targeted studies previously identified the BH3-only proteins Puma, Bim and Bid to have a role in ischemic/hypoxic neuronal injury. We here investigated the transcriptional activation of pro-apoptotic BH3-only proteins after OGD-induced injury in murine neocortical neurons. We observed a potent and early upregulation of noxa at mRNA and protein level, and a significant increase in Bmf protein levels during OGD in neocortical neurons and in the ipsilateral cortex of mice subjected to transient middle cerebral artery occlusion (tMCAO). Surprisingly, gene deficiency in noxa reduced neither OGD- nor glutamate-induced neuronal injury in cortical neurons and failed to influence infarct size or neurological deficits after tMCAO. In contrast, bmf deficiency induced significant protection against OGD- or glutamate-induced injury in cultured neurons, and bmf-deficient mice showed reduced neurological deficits after tMCAO in vivo. Collectively, our data not only point to a role of Bmf as a BH3-only protein contributing to excitotoxic and ischemic neuronal injury but also demonstrate that the early and potent induction of noxa does not influence ischemic neuronal injury.

  12. Cloning of a Serratia marcescens DNA fragment that induces quinoprotein glucose dehydrogenase-mediated gluconic acid production in Escherichia coli in the presence of stationary phase Serratia marcescens.

    Science.gov (United States)

    Krishnaraj, P U; Goldstein, A H

    2001-12-18

    Serratia marcescens ER2 was isolated from an endorhizosphere sample based on its high level of mineral phosphate solubilizing (MPS) activity. This phenotype was correlated with expression of the direct oxidation pathway. An ER2 plasmid library constructed in Escherichia coli strain DH5alpha was screened for MPS activity. A recombinant clone DH5alpha (pKG3791) was capable of gluconic acid (GA) production and tricalcium phosphate solubilization but only in the presence of stationary phase ER2 cells. GA production in DH5alpha (pKG3791) was apparently the result of the quinoprotein glucose dehydrogenase activity because AG121 (a Tn5 knockout of gcd) carrying pKG3791 did not produce GA under the same conditions. GA production by DH5alpha (pKG3791) was not observed when ER2 was replaced by another PQQ-producing strain bacterium. These data add to a growing body of evidence that E. coli contains some type of PQQ biosynthesis pathway distinct from those previously characterized in Gram-negative bacteria and that these genes may be induced under appropriate conditions.

  13. Augmented Reality Comes to Physics

    Science.gov (United States)

    Buesing, Mark; Cook, Michael

    2013-01-01

    Augmented reality (AR) is a technology used on computing devices where processor-generated graphics are rendered over real objects to enhance the sensory experience in real time. In other words, what you are really seeing is augmented by the computer. Many AR games already exist for systems such as Kinect and Nintendo 3DS and mobile apps, such as…

  14. Augmented Reality Comes to Physics

    Science.gov (United States)

    Buesing, Mark; Cook, Michael

    2013-01-01

    Augmented reality (AR) is a technology used on computing devices where processor-generated graphics are rendered over real objects to enhance the sensory experience in real time. In other words, what you are really seeing is augmented by the computer. Many AR games already exist for systems such as Kinect and Nintendo 3DS and mobile apps, such as…

  15. INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Min, Joong Won [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Kwang Il [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Hyun-Ah; Kim, Eun-Kyu; Noh, Woo Chul [Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Jeon, Hong Bae [Biomedical Research Institute, MEDIPOST Co., Ltd., Seoul (Korea, Republic of); Cho, Dong-Hyung [Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do (Korea, Republic of); Oh, Jeong Su [Department of Genetic Engineering, Sungkyunkwan University, Suwon (Korea, Republic of); Park, In-Chul; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Jae-Sung, E-mail: jaesung@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2013-10-11

    Highlights: •HIF-1α-regulated INPP4B enhances glycolysis. •INPP4B regulates aerobic glycolysis by inducing HK2 via Akt-mTOR pathway. •Blockage of INPP4B and HK2 sensitizes radioresistant laryngeal cancer cells to radiation and anticancer drug. •INPP4B is associated with HK2 in human laryngeal cancer tissues. -- Abstract: Inositol polyphosphate 4-phosphatase type II (INPP4B) was recently identified as a tumor resistance factor in laryngeal cancer cells. Herein, we show that INPP4B-mediated resistance is associated with increased glycolytic phenotype. INPP4B expression was induced by hypoxia and irradiation. Intriguingly, overexpression of INPP4B enhanced aerobic glycolysis. Of the glycolysis-regulatory genes, hexokinase 2 (HK2) was mainly regulated by INPP4B and this regulation was mediated through the Akt-mTOR pathway. Notably, codepletion of INPP4B and HK2 markedly sensitized radioresistant laryngeal cancer cells to irradiation or anticancer drug. Moreover, INPP4B was significantly associated with HK2 in human laryngeal cancer tissues. Therefore, these results suggest that INPP4B modulates aerobic glycolysis via HK2 regulation in radioresistant laryngeal cancer cells.

  16. Inhibition of PKCgamma membrane translocation mediated morphine preconditioning-induced neuroprotection against oxygen-glucose deprivation in the hippocampus slices of mice.

    Science.gov (United States)

    Liu, Ya; Li, Junfa; Yang, Jing; Ji, Fang; Bu, Xiangning; Zhang, Nan; Zhang, Bingxi

    2008-10-17

    We previously reported that novel protein kinase C (nPKC) epsilon and N-methyl-d-aspartic acid (NMDA) receptors participated in morphine preconditioning (MP)-induced neuroprotection. In this study, we used Western blot analysis, 2,3,5-triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH) leakage assay to determine the involvement of conventional PKC isoforms (cPKC) in MP-induced neuroprotection against oxygen-glucose deprivation (OGD). Hippocampus slices (400-microm thickness) from healthy male BALB/c mice exposed to OGD for 5-45 min to mimic mild, moderate and severe ischemia in the presence of MP pretreatment. We found that OGD-induced damage in neuronal cell survival rate and LDH leakage could be improved by MP pretreatment (3 microM) within 20 min of OGD, which was abolished by concomitant incubation with non-selective opioid receptor antagonist naloxone (Nal, 50 microM). The results of Western blot analysis showed that only cPKCgamma membrane translocation, not alpha, betaI and betaII, increased under the condition of OGD 10 min and 2h reperfusion (OGD/2h), and this increment of cPKCgamma membrane translocation was inhibited by MP pretreatment. To further elucidate the role of cPKCgamma in MP-induced neuroprotection, we found that cPKCgamma membrane translocation inhibitor, Go6983 (6 nM) did not affect MP-induced neuroprotection while Go6983 alone exhibited a significant inhibition on OGD-induced increment in LDH leakage and decrease in cell survival rate. These phenomena were defined by the results that Go6983 could restore OGD-induced cPKCgamma membrane translocation, but had no further effect on MP-induced inhibition of cPKCgamma membrane translocation. These results demonstrated that MP can reduce OGD-induced neuronal injuries, and the down-regulation of cPKCgamma membrane translocation might be involved in the neuroprotection.

  17. Oxygen-glucose deprivation increases the enzymatic activity and the microvesicle-mediated release of ectonucleotidases in the cells composing the blood-brain barrier.

    Science.gov (United States)

    Ceruti, Stefania; Colombo, Laura; Magni, Giulia; Viganò, Francesca; Boccazzi, Marta; Deli, Mária A; Sperlágh, Beáta; Abbracchio, Maria P; Kittel, Agnes

    2011-08-01

    The blood-brain barrier (BBB), the dynamic interface between the nervous tissue and the blood, is composed by endothelial cells, pericytes and astrocytes. Extracellular nucleotides and nucleosides and their receptors (the purinergic system) constitute a widely diffused signaling system involved in many pathophysiological processes. However, the role of this system in controlling BBB functions is still largely unknown. By using cultures of these three cell types grown separately and a BBB in vitro model consisting of triple co-cultures, we studied for the first time the expression and distribution of the ecto-enzymes nucleoside triphosphate diphosphohydrolases (NTPDases, the enzymes which hydrolyze extracellular nucleotides) under control and ischemic (oxygen-glucose deprivation in vitro; OGD) conditions. NTPDase1 was detected in all three cell types, whereas NTPDase2 was expressed by astrocytes and pericytes and, to a lesser extent, by endothelial cells. Endothelial cells were extremely susceptible to cell death when OGD was applied to mimic in vitro the cytotoxicity induced by ischemia, whereas astrocytes and pericytes were more resistant. A semi-quantitative assay highlighted markedly increased e-ATPase activity following exposure to OGD in all three cell types, either when grown separately or when co-cultured together to resemble the composition of the BBB. Moreover, electron microscopy analysis showed that both endothelial cells and astrocytes shed microvesicles containing NTPDases from their membrane, which may suggest a novel mechanism to increase the breakdown of ATP released to toxic levels by damaged BBB cells. We hypothesize that this phenomenon could have a protective and/or modulatory effect for brain parenchymal cells. This in vitro model is therefore useful to study the role of extracellular nucleotides in modulating BBB responses to ischemic events, and to develop new effective purinergic-based approaches for brain ischemia.

  18. Analysis of 18F-fluorodeoxy-glucose PET imaging data captured before and after Pc 4-mediated photodynamic therapy of U87 tumors in the athymic nude rat

    Science.gov (United States)

    Cross, Nathan; Varghai, Davood; Spring-Robinson, Chandra; Sharma, Rahul; Muzic, Raymond F., Jr.; Oleinick, Nancy L.; Dean, D.

    2007-02-01

    Introduction: Several workers have proposed the use of PET (Positron Emission Tomography) imaging for the outcome assessment of photodynamic therapy (PDT), especially for deep-seated tumors. We report on our study of 18Ffluorodeoxy- glucose (18F-FDG) PET imaging following brain tumor Pc4-PDT. Our working hypothesis was that the tumor's metabolic activity would decline dramatically following Pc 4-PDT owing to tumor necrosis. Methods: Seven days after intraparenchymal implantation of U87 cells, the brains of 12 athymic nude rats were imaged by micro-CT and/or micro-MR. These animals were also 18F-FDG micro-PET (μPET) scanned before and after Pc 4-PDT. 18F-FDG was used to trace metabolic activity that was monitored via μPET. Occurrence of PDT was confirmed on histology. The analysis of 18F-FDG dose and animal weight normalized μPET activity was studied over the 90 minute µPET scan. Results: Currently, μPET data have been studied for: (1) three of the animals that did not indicate tumor necrosis on histology and were assigned to a "Non-PDT" group, and (2) six animals that exhibited tumor necrosis on histology and were assigned to a "PDT" group. The μPET-detected 18F-FDG uptake activity in the tumor region before and after photoirradiation increased in the Non-PDT group an average of 2.28 times, and in the PDT group it increased an average of 1.15 times. Discussion: We are investigating the cause of the increase in 18F-FDG μPET activity that we observed in the PDT group. The methodology used in this study should be useful in determining whether this or other PET, SPECT, or MR functional imaging protocols will detect both the specificity and sensitivity of brain tumor necrosis following Pc 4-PDT.

  19. Monitoring Pc 4-mediated photodynamic therapy of U87 tumors with 18F- fluorodeoxy-glucose PET imaging in the Athymic Nude Rat

    Science.gov (United States)

    Varghai, Davood; Cross, Nathan; Spring-Robinson, Chandra; Sharma, Rahul; Feyes, Denise K.; Ahmad, Yusra; Oleinick, Nancy L.; Muzic, Raymond F., Jr.; Dean, David

    2007-02-01

    Introduction: We have previously demonstrated the use of phthalocyanine Pc 4 for the photodynamic therapy (PDT) of ectopic human glial tumors in the athymic nude rat brain. We wish to determine whether 18F-fluorodeoxy-glucose ( 18F-FDG) Positron Emission Tomography (PET) imaging can detect the reduction in tumor metabolism that must occur after Pc 4-PDT-induced necrosis. Methods: 2.5 x 10 5 U87 cells were injected into the brains of 12 athymic nude rats. After 7 days of tumor growth, all 12 animals were imaged functionally by 18F-FDG micro-PET (μPET) and structurally by micro-CT and/or micro-MR. These animals received 0.5 mg/kg b.w. Pc 4 via tail-vein injection. One day later the scalp was re-incised and the tumor illuminated with 30 J/cm2 of 672-nm light from a diode laser. The next day these animals were again 18F-FDG μPET imaged. Next, the animals were euthanized and their brains were explanted for H&E histology. Results: Histology showed that tumors in the 6 Pc 4-PDT-treated animals demonstrated necrosis ranging from full to frank (severe). Preliminary analysis showed that 18F-FDG μPET activity in 3 of the 6 non-PDT group (i.e., no tumor necrosis observed) animals was seen to increase 2.28 times following tumor photoirradiation, whereas 18F-FDG μPET activity in 5 of the 6 PDT group (i.e., tumor necrosis observed) animals was seen to increase 1.15 times following tumor photoirradiation. Discussion: The increased 18F-FDG μPET activity in the PDT group was unexpected. We had expected this activity to decrease and are presently investigating the cause of this observation.

  20. Biocatalytic anode for glucose oxidation utilizing carbon nanotubes for direct electron transfer with glucose oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Vaze, Abhay; Hussain, Nighat; Tang, Chi [Department of Chemistry, University of Connecticut, Storrs, CT 06269-3060 (United States); Leech, Donal [School of Chemistry, National University of Ireland, Galway (Ireland); Rusling, James [Department of Chemistry, University of Connecticut, Storrs, CT 06269-3060 (United States); Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06032 (United States); School of Chemistry, National University of Ireland, Galway (Ireland)

    2009-10-15

    Covalently linked layers of glucose oxidase, single-wall carbon nanotubes and poly-L-lysine on pyrolytic graphite resulted in a stable biofuel cell anode featuring direct electron transfer from the enzyme. Catalytic response observed upon addition of glucose was due to electrochemical oxidation of FADH{sub 2} under aerobic conditions. The electrode potential depended on glucose concentration. This system has essential attributes of an anode in a mediator-free biocatalytic fuel cell. (author)

  1. Application of Semipermeable Membranes in Glucose Biosensing

    Directory of Open Access Journals (Sweden)

    Tanmay Kulkarni

    2016-12-01

    Full Text Available Glucose biosensors have received significant attention in recent years due to the escalating mortality rate of diabetes mellitus. Although there is currently no cure for diabetes mellitus, individuals living with diabetes can lead a normal life by maintaining tight control of their blood glucose levels using glucose biosensors (e.g., glucometers. Current research in the field is focused on the optimization and improvement in the performance of glucose biosensors by employing a variety of glucose selective enzymes, mediators and semipermeable membranes to improve the electron transfer between the active center of the enzyme and the electrode substrate. Herein, we summarize the different semipermeable membranes used in the fabrication of the glucose biosensor, that result in improved biosensor sensitivity, selectivity, dynamic range, response time and stability.

  2. Adapting Information Through Tangible Augmented Reality Interfaces

    OpenAIRE

    Sinclair, Patrick; Martinez, Kirk

    2004-01-01

    Tangible augmented reality interfaces offer a hands on approach for examining objects and exploring the associated information. We describe two tangible augmented reality interfaces that can expose the adaptation of information presented to users about objects in augmented reality environments.

  3. Magnetohydrodynamic Augmented Propulsion Experiment

    Science.gov (United States)

    Litchford, Ron J.; Cole, John; Lineberry, John; Chapman, Jim; Schmidt, Harold; Cook, Stephen (Technical Monitor)

    2002-01-01

    A fundamental obstacle to routine space access is the specific energy limitations associated with chemical fuels. In the case of vertical take-off, the high thrust needed for vertical liftoff and acceleration to orbit translates into power levels in the 10 GW range. Furthermore, useful payload mass fractions are possible only if the exhaust particle energy (i.e., exhaust velocity) is much greater than that available with traditional chemical propulsion. The electronic binding energy released by the best chemical reactions (e.g., LOX/LH2 for example, is less than 2 eV per product molecule (approx. 1.8 eV per H2O molecule), which translates into particle velocities less than 5 km/s. Useful payload fractions, however, will require exhaust velocities exceeding 15 km/s (i.e., particle energies greater than 20 eV). As an added challenge, the envisioned hypothetical RLV (reusable launch vehicle) should accomplish these amazing performance feats while providing relatively low acceleration levels to orbit (2-3g maximum). From such fundamental considerations, it is painfully obvious that planned and current RLV solutions based on chemical fuels alone represent only a temporary solution and can only result in minor gains, at best. What is truly needed is a revolutionary approach that will dramatically reduce the amount of fuel and size of the launch vehicle. This implies the need for new compact high-power energy sources as well as advanced accelerator technologies for increasing engine exhaust velocity. Electromagnetic acceleration techniques are of immense interest since they can be used to circumvent the thermal limits associated with conventional propulsion systems. This paper describes the Magnetohydrodynamic Augmented Propulsion Experiment (MAPX) being undertaken at NASA Marshall Space Flight Center (MSFC). In this experiment, a 1-MW arc heater is being used as a feeder for a 1-MW magnetohydrodynamic (MHD) accelerator. The purpose of the experiment is to demonstrate

  4. Deletion of TRPC6 Attenuates NMDA Receptor-Mediated Ca2+ Entry and Ca2+-Induced Neurotoxicity Following Cerebral Ischemia and Oxygen-Glucose Deprivation

    Science.gov (United States)

    Chen, Jin; Li, Zhaozhong; Hatcher, Jeffery T.; Chen, Qing-Hui; Chen, Li; Wurster, Robert D.; Chan, Sic L.; Cheng, Zixi

    2017-01-01

    Transient receptor potential canonical 6 (TRPC6) channels are permeable to Na+ and Ca2+ and are widely expressed in the brain. In this study, the role of TRPC6 was investigated following ischemia/reperfusion (I/R) and oxygen-glucose deprivation (OGD). We found that TRPC6 expression was increased in wild-type (WT) mice cortical neurons following I/R and in primary neurons with OGD, and that deletion of TRPC6 reduced the I/R-induced brain infarct in mice and the OGD- /neurotoxin-induced neuronal death. Using live-cell imaging to examine intracellular Ca2+ levels ([Ca2+]i), we found that OGD induced a significant higher increase in glutamate-evoked Ca2+ influx compared to untreated control and such an increase was reduced by TRPC6 deletion. Enhancement of TRPC6 expression using AdCMV-TRPC6-GFP infection in WT neurons increased [Ca2+]i in response to glutamate application compared to AdCMV-GFP control. Inhibition of N-methyl-d-aspartic acid receptor (NMDAR) with MK801 decreased TRPC6-dependent increase of [Ca2+]i in TRPC6 infected cells, indicating that such a Ca2+ influx was NMDAR dependent. Furthermore, TRPC6-dependent Ca2+ influx was blunted by blockade of Na+ entry in TRPC6 infected cells. Finally, OGD-enhanced Ca2+ influx was reduced, but not completely blocked, in the presence of voltage-dependent Na+ channel blocker tetrodotoxin (TTX) and dl-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) blocker CNQX. Altogether, we concluded that I/R-induced brain damage was, in part, due to upregulation of TRPC6 in cortical neurons. We postulate that overexpression of TRPC6 following I/R may induce neuronal death partially through TRPC6-dependent Na+ entry which activated NMDAR, thus leading to a damaging Ca2+ overload. These findings may provide a potential target for future intervention in stroke-induced brain damage.

  5. Phenobarbital Augments Hypothermic Neuroprotection

    Science.gov (United States)

    Barks, John D.; Liu, Yi-Qing; Shangguan, Yu; Silverstein, Faye S.

    2010-01-01

    Seizures are associated with adverse outcome in infants with hypoxic-ischemic encephalopathy. We hypothesized that early administration of the anticonvulsant phenobarbital after cerebral hypoxia-ischemia could enhance the neuroprotective efficacy of delayed-onset hypothermia. We tested this hypothesis in a neonatal rodent model. Seven-day-old rats (n=104) underwent right carotid ligation, followed by 90 min 8%O2 exposure; 15 min later, they received injections of phenobarbital (40 mg/kg) or saline. One or 3h later, all were treated with hypothermia (30°C, 3h). Function and neuropathology were evaluated after 7 days (“early outcomes”) or 1 month (“late outcomes”). Early outcome assessment demonstrated better sensorimotor performance and less cortical damage in phenobarbital-treated groups; there were no differences between groups in which the hypothermia delay was shortened from 3h to 1h. Late outcome assessment confirmed sustained benefits of phenobarbital+hypothermia treatment; sensorimotor performance was better (persistent attenuation of contralateral forepaw placing deficits and absence of contralateral forepaw neglect); neuropathology scores were lower (medians, phenobarbital 2, saline 8.5, pphenobarbital may augment the neuroprotective efficacy of therapeutic hypothermia. PMID:20098339

  6. Augmented Likelihood Image Reconstruction.

    Science.gov (United States)

    Stille, Maik; Kleine, Matthias; Hägele, Julian; Barkhausen, Jörg; Buzug, Thorsten M

    2016-01-01

    The presence of high-density objects remains an open problem in medical CT imaging. Data of projections passing through objects of high density, such as metal implants, are dominated by noise and are highly affected by beam hardening and scatter. Reconstructed images become less diagnostically conclusive because of pronounced artifacts that manifest as dark and bright streaks. A new reconstruction algorithm is proposed with the aim to reduce these artifacts by incorporating information about shape and known attenuation coefficients of a metal implant. Image reconstruction is considered as a variational optimization problem. The afore-mentioned prior knowledge is introduced in terms of equality constraints. An augmented Lagrangian approach is adapted in order to minimize the associated log-likelihood function for transmission CT. During iterations, temporally appearing artifacts are reduced with a bilateral filter and new projection values are calculated, which are used later on for the reconstruction. A detailed evaluation in cooperation with radiologists is performed on software and hardware phantoms, as well as on clinically relevant patient data of subjects with various metal implants. Results show that the proposed reconstruction algorithm is able to outperform contemporary metal artifact reduction methods such as normalized metal artifact reduction.

  7. Understanding augmented reality concepts and applications

    CERN Document Server

    Craig, Alan B

    2013-01-01

    Augmented reality is not a technology. Augmented reality is a medium. Likewise, a book on augmented reality that only addresses the technology that is required to support the medium of augmented reality falls far short of providing the background that is needed to produce, or critically consume augmented reality applications. One reads a book. One watches a movie. One experiences augmented reality. Understanding Augmented Reality addresses the elements that are required to create compelling augmented reality experiences. The technology that supports

  8. Augmented reality som wearable technology

    DEFF Research Database (Denmark)

    Rahn, Annette

    2016-01-01

    “How Augmented reality can facilitate learning in visualizing human anatomy “ At this station I demonstrate how Augmented reality can be used to visualize the human lungs in situ and as a wearable technology which establish connection between body, image and technology in education. I will show...... the potential of Augmented reality increasing students level of understanding, interaction and engagement with the object. I will demonstrate the technology and show you the human lungs in your body and the future perspectives of the technology. Organization: developed in collaboration with Mie Buhl, Professor...

  9. Navigation in Augmented Reality, Navigation i Augmented Reality

    OpenAIRE

    Bernelind, Sarah

    2015-01-01

    The concept of augmented reality has existed since the 60’s. In this thesis it has been investigated if navigation using a mobile device would benefit, from a usability perspective, if the navigational data were presented using augmented reality instead of a standardized map. The usability principles from which the applications were evaluated are learnability, user satisfaction, efficiency and effectivity. An AR prototype was developed and tested against a standard map, in the form of Google ...

  10. Decreased serum glucose and glycosylated hemoglobin levels in patients with Chuvash polycythemia: a role for HIF in glucose metabolism

    OpenAIRE

    McClain, Donald A.; Abuelgasim, Khadega A; Nouraie, Mehdi; Salomon-Andonie, Juan; Niu, Xiaomei; Miasnikova, Galina; Polyakova, Lydia A.; Sergueeva, Adelina; Okhotin, Daniel J.; Cherqaoui, Rabia; Okhotin, David; Cox, James E.; Swierczek, Sabina; Song, Jihyun; Simon, M. Celeste

    2012-01-01

    In Chuvash polycythemia, a homozygous 598C>T mutation in the von Hippel-Lindau gene (VHL) leads to an R200W substitution in VHL protein, impaired degradation of α-subunits of hypoxia inducible factor (HIF)-1 and HIF-2, and augmented hypoxic responses during normoxia. Chronic hypoxia of high altitude is associated with decreased serum glucose and insulin concentrations. Other investigators reported that HIF-1 promotes cellular glucose uptake by increased expression of GLUT1 and increased glyco...

  11. Low Blood Glucose (Hypoglycemia)

    Science.gov (United States)

    ... Disease, & Other Dental Problems Diabetes & Sexual & Urologic Problems Low Blood Glucose (Hypoglycemia) What is hypoglycemia? Hypoglycemia, also called low blood glucose or low blood sugar, occurs when ...

  12. Sevoflurane post-conditioning protects primary rat cortical neurons against oxygen-glucose deprivation/resuscitation via down-regulation in mitochondrial apoptosis axis of Bid, Bim, Puma-Bax and Bak mediated by Erk1/2.

    Science.gov (United States)

    Zhang, Li-Min; Zhao, Xiao-Chun; Sun, Wen-Bo; Li, Rui; Jiang, Xiao-Jing

    2015-10-15

    Temporal post-conditioning helps provide neuroprotection against brain injury secondary to ischemia-reperfusion and is considered an effective intervention, but the exact mechanism of sevoflurane post-conditioning is unclear. The essential axis involves activator Bid, Bim, Puma (BH3s), Bax, and Bak; activates the mitochondrial death program; and might be involved in a cell death signal. Extracellular signal-related kinases 1/2 (Erk1/2) play a pivotal role in cell growth and proliferation. We hypothesized that sevoflurane post-conditioning might inhibit Bid, Bim, Puma, Bax, and Bak expression and is activated by phosphor-Erk1/2 to decrease neuronal death. To test this hypothesis, we exposed primary cortical neuron cultures to oxygen-glucose deprivation for 1h, along with resuscitation for 24h (OGD/R). MTT assays, propidium iodide uptake (PI), JC-1 fluorescence, and Western blot indicated the following: decreased cell viability (PPuma, Bax, and Bak expression with OGD/R exposure. Inhibition of Erk1/2 phosphorylation could attenuate sevoflurane post-conditioning that mediated an increase in neuronal viability and mitochondrial membrane potential, as well as a decrease in cell death and Bid, Bim, Puma, Bax, and Bak expression after OGD/R treatment. The results demonstrated that sevoflurane post-conditioning caused a marked decrease in cortical neuronal death secondary to OGD/R exposure through the downregulation of the mitochondrial apoptosis axis involving Bid, Bim, Puma, Bax, and Bak that was mediated by the phosphorylation/activation of Erk1/2.

  13. Mersiline mesh in premaxillary augmentation.

    Science.gov (United States)

    Foda, Hossam M T

    2005-01-01

    Premaxillary retrusion may distort the aesthetic appearance of the columella, lip, and nasal tip. This defect is characteristically seen in, but not limited to, patients with cleft lip nasal deformity. This study investigated 60 patients presenting with premaxillary deficiencies in which Mersiline mesh was used to augment the premaxilla. All the cases had surgery using the external rhinoplasty technique. Two methods of augmentation with Mersiline mesh were used: the Mersiline roll technique, for the cases with central symmetric deficiencies, and the Mersiline packing technique, for the cases with asymmetric deficiencies. Premaxillary augmentation with Mersiline mesh proved to be simple technically, easy to perform, and not associated with any complications. Periodic follow-up evaluation for a mean period of 32 months (range, 12-98 months) showed that an adequate degree of premaxillary augmentation was maintained with no clinically detectable resorption of the mesh implant.

  14. Profiling the dynamics of abscisic acid and ABA-glucose ester after using the glucosyltransferase UGT71C5 to mediate abscisic acid homeostasis in Arabidopsis thaliana by HPLC-ESI-MS/MS

    Institute of Scientific and Technical Information of China (English)

    Dong-Mei Xiong; Zhen Liu; Han Chen; Jin-Tao Xue; Yi Yang; Cong Chen; Li-Ming Ye

    2014-01-01

    The HPLC-MS/MS method was developed to profile the dynamics of abscisic acid (ABA) and ABA-glucose ester (ABA-GE) after cloning glycosyltransferase enzyme family gene AtUGT71C5 into Arabidopsis thaliana. By constructing over-expression lines (OE) and down-expression lines (DN), we acquired mutant strains to analyze the function of AtUGT71C5. The multiple-reaction monitoring (MRM) was used for quantitative determination in negative mode. The transition was m/z 263.1-153.0 for ABA ([M-H]þ), m/z 425.1-263.0 for ABA-GE ([M-H]þ), and m/z 321.0-152.0 for chloramphe-nicol. The linear range was 0.8684-217.1 ng/mL for ABA and 0.3920-196.0 ng/mL for ABA-GE. The accuracy was 88.0-109.0% for ABA and 86.6-113.0% for ABA-GE; the inter-day and intra-day precisions were less than 5.4%for ABA and 8.9%for ABA-GE, respectively. This method is simple and sensitive enough for determination of ABA and ABA-GE in A. thaliana leaves. All the evidence confirmed the speculation that AtUGT71C5 can mediate abscisic acid homeostasis.

  15. AMP-activated protein kinase acts as a negative regulator of high glucose-induced RANKL expression in human periodontal ligament cells

    Institute of Scientific and Technical Information of China (English)

    FENG Yuan; LIU Jia-qiang; LIU Hong-chen

    2012-01-01

    Background It is well known that the function of periodontal ligament cells may be affected by high glucose levels.This study investigated the direct effect of high glucose on the expression of receptor activator of nuclear factor-kappa B ligand (RANKL) in human PDL (hPDL) cells.In addition,we examined whether this effect was mediated via AMPK activation.Methods We examined the expression of osteoprotegerin in hPDL cells cultured at different concentrations of glucose using real-time polymerase chain reaction (PCR),and Western blotting analysis.AMPK phosphorylation in hPDL cells was studied using immunoprecipitate kinase assay and Western blotting.The effect of AMPK activation on RANKL expression in hPDL cells was investigated by real-time PCR and Western blotting.Results High glucose levels caused an increase in RANKL mRNA and protein expression in hPDL cells.Moreover,the amount of p-AMPK and AMPK activity was lower in hPDL cells exposed to high glucose levels than in cells exposed to normal glucose levels.Suppression of AMPK by Compound C augmented RANKL expression,and AMPK activation by metformin significantly decreased RANKL expression in hPDL cells.Additionally,metformin down-regulated RANKL expression in hPDL cells exposed to high glucose via AMPK activation.Conclusion High glucose-induced up-regulation of RANKL could be due to decreased AMPK activity,and AMPK activation may be involved in regulating of RANKL expression in hPDL cells.

  16. Pure Laparoscopic Augmentation Ileocystoplasty

    Directory of Open Access Journals (Sweden)

    Rafael B. Rebouças

    2014-12-01

    Full Text Available Introduction Guillain-Barre syndrome is an acute neuropathy that rarely compromises bladder function. Conservative management including clean intermittent catheterization and pharmacotherapy is the primary approach for hypocompliant contracted bladder. Surgical treatment may be used in refractory cases to improve bladder compliance and capacity in order to protect the upper urinary tract. We describe a case of pure laparoscopic augmentation ileocystoplasty in a patient affected by Guillain-Barre syndrome. Presentation A 15-year-old female, complaining of voiding dysfunction, recurrent urinary tract infection and worsening renal function for three months. A previous history of Guillain-Barre syndrome on childhood was related. A voiding cystourethrography showed a pine-cone bladder with moderate post-void residual urine. The urodynamic demonstrated a hypocompliant bladder and small bladder capacity (190mL with high detrusor pressure (54 cmH2O. Nonsurgical treatments were attempted, however unsuccessfully. The patient was placed in the exaggerated Trendelenburg position. A four-port transperitoneal technique was used. A segment of ileum approximately 15-20cm was selected and divided with its pedicle. The ileal anastomosis and creation of ileal U-shaped plate were performed laparoscopically, without staplers. Bladder mobilization and longidutinal cystotomy were performed. Enterovesical anastomosis was done with continuous running suture. A suprapubic cystostomy was placed through a 5mm trocar. Results The total operative time was 335 min. The blood loss was minimal. The patient developed ileus in the early days, diet acceptance after the fourth day and was discharged on the seventh postoperative day. The urethral catheter was removed after 2 weeks. At 6-month follow-up, a cystogram showed a significant improvement in bladder capacity. The patient adhered well to clean intermittent self-catheterization and there was no report for febrile infections

  17. Glucose sensor excludes hypoglycaemia as cause of death

    DEFF Research Database (Denmark)

    Schmidt, Signe; Nørgaard, Kirsten

    2012-01-01

    The cause of death can be difficult to verify post-mortem in unexpected deaths in patients with Type 1 diabetes. This report describes an unexpected death in a 44-year-old man with Type 1 diabetes treated with sensor-augmented pump therapy. Continuous glucose monitoring data proved useful...

  18. Enhancement of glucose transport by selected plant foods in muscle cell line L6.

    Science.gov (United States)

    Noipha, K; Ratanachaiyavong, S; Ninla-Aesong, P

    2010-08-01

    Glucose uptake activity of 11 plant foods was assessed in L6 myotubes. Among them onion and ginger showed potent enhancement of glucose transport. This effect required new protein synthesis of glucose transporters. In addition, onion-induced glucose uptake in L6 myotubes was mediated through activation of phosphoinositide 3-kinase.

  19. Bayesian Alternation During Tactile Augmentation

    Directory of Open Access Journals (Sweden)

    Caspar Mathias Goeke

    2016-10-01

    Full Text Available A large number of studies suggest that the integration of multisensory signals by humans is well described by Bayesian principles. However, there are very few reports about cue combination between a native and an augmented sense. In particular, we asked the question whether adult participants are able to integrate an augmented sensory cue with existing native sensory information. Hence for the purpose of this study we build a tactile augmentation device. Consequently, we compared different hypotheses of how untrained adult participants combine information from a native and an augmented sense. In a two-interval forced choice (2 IFC task, while subjects were blindfolded and seated on a rotating platform, our sensory augmentation device translated information on whole body yaw rotation to tactile stimulation. Three conditions were realized: tactile stimulation only (augmented condition, rotation only (native condition, and both augmented and native information (bimodal condition. Participants had to choose one out of two consecutive rotations with higher angular rotation. For the analysis, we fitted the participants’ responses with a probit model and calculated the just notable difference (JND. Then we compared several models for predicting bimodal from unimodal responses. An objective Bayesian alternation model yielded a better prediction (χred2 = 1.67 than the Bayesian integration model (χred2= 4.34. Slightly higher accuracy showed a non-Bayesian winner takes all model (χred2= 1.64, which either used only native or only augmented values per subject for prediction. However the performance of the Bayesian alternation model could be substantially improved (χred2= 1.09 utilizing subjective weights obtained by a questionnaire. As a result, the subjective Bayesian alternation model predicted bimodal performance most accurately among all tested models. These results suggest that information from augmented and existing sensory modalities in

  20. Augmented Reality Tower Technology Assessment

    Science.gov (United States)

    Reisman, Ronald J.; Brown, David M.

    2009-01-01

    Augmented Reality technology may help improve Air Traffic Control Tower efficiency and safety during low-visibility conditions. This paper presents the assessments of five off-duty controllers who shadow-controlled' with an augmented reality prototype in their own facility. Initial studies indicated unanimous agreement that this technology is potentially beneficial, though the prototype used in the study was not adequate for operational use. Some controllers agreed that augmented reality technology improved situational awareness, had potential to benefit clearance, control, and coordination tasks and duties and could be very useful for acquiring aircraft and weather information, particularly aircraft location, heading, and identification. The strongest objections to the prototype used in this study were directed at aircraft registration errors, unacceptable optical transparency, insufficient display performance in sunlight, inadequate representation of the static environment and insufficient symbology.

  1. Therapeutic options for lip augmentation.

    Science.gov (United States)

    Segall, Lorne; Ellis, David A F

    2007-11-01

    Aesthetic ideals vary with emerging fashion trends and within different cultures. However, over the past few decades, fuller lips have been considered a desirable trait. Many younger patients are presenting for lip augmentation to achieve the sought-after look commonly seen in many fashion magazines. In addition, as individuals age, they lose lip volume, with a thinning of the red lip, some effacement of the vermillion border, and elongation and flattening of the white portion of the lip. Rejuvenation of the lips plays a key role in restoring a more youthful appearance. As a result, lip augmentation appeals to a wide spectrum of patients who present with various different aesthetic goals and expectations. Numerous therapeutic options exist for aesthetic lip augmentation, ranging from temporary and permanent injectable fillers to implants and other surgical techniques.

  2. Improvement of gemcitabine sensitivity of p53-mutated pancreatic cancer MiaPaCa-2 cells by RUNX2 depletion-mediated augmentation of TAp73-dependent cell death

    Science.gov (United States)

    Nakamura, M; Sugimoto, H; Ogata, T; Hiraoka, K; Yoda, H; Sang, M; Sang, M; Zhu, Y; Yu, M; Shimozato, O; Ozaki, T

    2016-01-01

    Pancreatic cancer exhibits the worst prognostic outcome among human cancers. Recently, we have described that depletion of RUNX2 enhances gemcitabine (GEM) sensitivity of p53-deficient pancreatic cancer AsPC-1 cells through the activation of TAp63-mediated cell death pathway. These findings raised a question whether RUNX2 silencing could also improve GEM efficacy on pancreatic cancer cells bearing p53 mutation. In the present study, we have extended our study to p53-mutated pancreatic cancer MiaPaCa-2 cells. Based on our current results, MiaPaCa-2 cells were much more resistant to GEM as compared with p53-proficient pancreatic cancer SW1990 cells, and there existed a clear inverse relationship between the expression levels of TAp73 and RUNX2 in response to GEM. Forced expression of TAp73α in MiaPaCa-2 cells significantly promoted cell cycle arrest and/or cell death, indicating that a large amount of TAp73 might induce cell death even in the presence of mutant p53. Consistent with this notion, overexpression of TAp73α stimulated luciferase activity driven by p53/TAp73-target gene promoters in MiaPaCa-2 cells. Similar to AsPC-1 cells, small interfering RNA-mediated knockdown of RUNX2 remarkably enhanced GEM sensitivity of MiPaCa-2 cells. Under our experimental conditions, TAp73 further accumulated in RUNX2-depleted MiaPaCa-2 cells exposed to GEM relative to GEM-treated non-silencing control cells. As expected, silencing of p73 reduced GEM sensitivity of MiPaCa-2 cells. Moreover, GEM-mediated Tyr phosphorylation level of TAp73 was much more elevated in RUNX2-depleted MiaPaCa-2 cells. Collectively, our present findings strongly suggest that knockdown of RUNX2 contributes to a prominent enhancement of GEM sensitivity of p53-mutated pancreatic cancer cells through the activation of TAp73-mediated cell death pathway, and also provides a promising strategy for the treatment of patients with pancreatic cancer bearing p53 mutation. PMID:27294865

  3. Geniposide regulates glucose-stimulated insulin secretion possibly through controlling glucose metabolism in INS-1 cells.

    Directory of Open Access Journals (Sweden)

    Jianhui Liu

    Full Text Available Glucose-stimulated insulin secretion (GSIS is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM. Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.

  4. Hepatic carboxylesterase 1 is induced by glucose and regulates postprandial glucose levels.

    Directory of Open Access Journals (Sweden)

    Jiesi Xu

    Full Text Available Metabolic syndrome, characterized by obesity, hyperglycemia, dyslipidemia and hypertension, increases the risks for cardiovascular disease, diabetes and stroke. Carboxylesterase 1 (CES1 is an enzyme that hydrolyzes triglycerides and cholesterol esters, and is important for lipid metabolism. Our previous data show that over-expression of mouse hepatic CES1 lowers plasma glucose levels and improves insulin sensitivity in diabetic ob/ob mice. In the present study, we determined the physiological role of hepatic CES1 in glucose homeostasis. Hepatic CES1 expression was reduced by fasting but increased in diabetic mice. Treatment of mice with glucose induced hepatic CES1 expression. Consistent with the in vivo study, glucose stimulated CES1 promoter activity and increased acetylation of histone 3 and histone 4 in the CES1 chromatin. Knockdown of ATP-citrate lyase (ACL, an enzyme that regulates histone acetylation, abolished glucose-mediated histone acetylation in the CES1 chromatin and glucose-induced hepatic CES1 expression. Finally, knockdown of hepatic CES1 significantly increased postprandial blood glucose levels. In conclusion, the present study uncovers a novel glucose-CES1-glucose pathway which may play an important role in regulating postprandial blood glucose levels.

  5. AUGMENTATION-RELATED BRAIN PLASTICITY

    Directory of Open Access Journals (Sweden)

    Giovanni eDi Pino

    2014-06-01

    Full Text Available Today, the anthropomorphism of the tools and the development of neural interfaces require reconsidering the concept of human-tools interaction in the framework of human augmentation. This review analyzes the plastic process that the brain undergoes when it comes into contact with augmenting artificial sensors and effectors and, on the other hand, the changes that the use of external augmenting devices produces in the brain.Hitherto, few studies investigated the neural correlates of augmentation, but clues on it can be borrowed from logically-related paradigms: sensorimotor training, cognitive enhancement, cross-modal plasticity, sensorimotor functional substitution, use and embodiment of tools.Augmentation modifies function and structure of a number of areas, i.e. primary sensory cortices shape their receptive fields to become sensitive to novel inputs. Motor areas adapt the neuroprosthesis representation firing-rate to refine kinematics. As for normal motor outputs, the learning process recruits motor and premotor cortices and the acquisition of proficiency decreases attentional recruitment, focuses the activity on sensorimotor areas and increases the basal ganglia drive on the cortex. Augmentation deeply relies on the frontoparietal network. In particular, premotor cortex is involved in learning the control of an external effector and owns the tool motor representation, while the intraparietal sulcus extracts its visual features. In these areas, multisensory integration neurons enlarge their receptive fields to embody supernumerary limbs. For operating an anthropomorphic neuroprosthesis, the mirror system is required to understand the meaning of the action, the cerebellum for the formation of its internal model and the insula for its interoception. In conclusion, anthropomorphic sensorized devices can provide the critical sensory afferences to evolve the exploitation of tools through their embodiment, reshaping the body representation and the

  6. Augmented reality for anatomical education.

    Science.gov (United States)

    Thomas, Rhys Gethin; John, Nigel William; Delieu, John Michael

    2010-03-01

    The use of Virtual Environments has been widely reported as a method of teaching anatomy. Generally such environments only convey the shape of the anatomy to the student. We present the Bangor Augmented Reality Education Tool for Anatomy (BARETA), a system that combines Augmented Reality (AR) technology with models produced using Rapid Prototyping (RP) technology, to provide the student with stimulation for touch as well as sight. The principal aims of this work were to provide an interface more intuitive than a mouse and keyboard, and to evaluate such a system as a viable supplement to traditional cadaver based education.

  7. Corticosterone, but not Glucose, Treatment Enables Fasted Adrenalectomized Rats to Survive Moderate Hemorrhage

    Science.gov (United States)

    Darlington, Daniel N.; Chew, Gordon; Ha, Taryn; Keil, Lanny C.; Dallman, Mary F.

    1990-01-01

    Fed adrenalectomized rats survive the stress of hemorrhage and hypovolemia, whereas fasted adrenalectomized rats become hypotensive and hypoglycemic after the first 90 min and die within 4 hours (h). We have studied the effects of glucose and corticosterone (B) infusions after hemorrhage as well as treatment with B at the time of adrenalectomy on the capacity of chronically prepared, conscious, fasted, adrenalectomized rats to survive hemorrhage. We have also measured the magnitudes of vasoactive hormone responses to hemorrhage. Maintenance of plasma glucose concentrations did not sustain life; however, treatment of rats at the time of adrenalectomy with B allowed 100 percent survival, and acute treatment of adrenalectomized rats at the time of hemorrhage allowed about 50 percent survival during the 5-h posthemorrhage observation period. Rats in the acute B infusion group that died exhibited significantly increased plasma B and significantly decreased plasma glucose concentrations by 2 h compared to the rats that lived. Plasma vasopressin, renin, and norepinephrine responses to hemorrhage were markedly augmented in the adrenalectomized rats not treated with B, and plasma vasopressin concentrations were significantly elevated at 1 and 2 h in all of the rats that subsequently died compared to values in those that lived. We conclude that: 1) death after hemorrhage in fasted adrenalectomized rats is not a result of lack of glucose; 2) chronic and, to an extent, acute treatment of fasted adrenalectomized rats with B enables survival; 3) fasted adrenalectomized rats exhibit strong evidence of hepatic insufficiency which is not apparent in either fed adrenalectomized rats or B-treated fasted adrenalectomized rats; 4) death after hemorrhage in fasted adrenalectomized rats may result from hepatic failure as a consequence of marked splanchnic vasoconstriction mediated bv the actions of extraordinarily high levels of vasoactive hormones after hemorrhage; and 5) B appears to

  8. Microbiofuel cell powered by glucose/O-2 based on electrodeposition of enzyme, conducting polymer and redox mediators. Part II : Influence of the electropolymerized monomer on the output power density and stability

    NARCIS (Netherlands)

    Ammam, Malika; Fransaer, Jan

    2014-01-01

    In this study, we investigated the influence of nature of the electropolymerized monomer on the resulting power output and stability of a glucose/O-2 powered biofuel cells (BFCs). The bioanode was prepared from a mixture of glucose oxidase-polymeric monomer-ferrocenium hexafluorophosphate-pyrroloqui

  9. The glucose metabolite methylglyoxal inhibits expression of the glucose transporter genes by inactivating the cell surface glucose sensors Rgt2 and Snf3 in yeast.

    Science.gov (United States)

    Roy, Adhiraj; Hashmi, Salman; Li, Zerui; Dement, Angela D; Cho, Kyu Hong; Kim, Jeong-Ho

    2016-03-01

    Methylglyoxal (MG) is a cytotoxic by-product of glycolysis. MG has inhibitory effect on the growth of cells ranging from microorganisms to higher eukaryotes, but its molecular targets are largely unknown. The yeast cell-surface glucose sensors Rgt2 and Snf3 function as glucose receptors that sense extracellular glucose and generate a signal for induction of expression of genes encoding glucose transporters (HXTs). Here we provide evidence that these glucose sensors are primary targets of MG in yeast. MG inhibits the growth of glucose-fermenting yeast cells by inducing endocytosis and degradation of the glucose sensors. However, the glucose sensors with mutations at their putative ubiquitin-acceptor lysine residues are resistant to MG-induced degradation. These results suggest that the glucose sensors are inactivated through ubiquitin-mediated endocytosis and degraded in the presence of MG. In addition, the inhibitory effect of MG on the glucose sensors is greatly enhanced in cells lacking Glo1, a key component of the MG detoxification system. Thus the stability of these glucose sensors seems to be critically regulated by intracellular MG levels. Taken together, these findings suggest that MG attenuates glycolysis by promoting degradation of the cell-surface glucose sensors and thus identify MG as a potential glycolytic inhibitor.

  10. Interference Reduction in Glucose Detection by Redox Potential Tuning: New Glucose Meter Development.

    Science.gov (United States)

    Cho, Seong Je; Cho, Chul-Ho; Kim, Kwang Bok; Lee, Min-Hyoung; Kim, Jae Hong; Lee, Suho; Cho, Jaegeol; Jung, Suntae; Kim, Dong-Min; Shim, Yoon-Bo

    2015-01-01

    A new glucose meter was developed employing a novel disposable glucose sensor strip comprising a nicotinamide adenine dinucleotide-glucose dehydrogenase (NAD-GDH) and a mixture of Fe compounds as a mediator. An iron complex, 5-(2,5-di(thiophen-2-yl)-1H-pyrrol-1-yl)-1,10-phenanthroline iron(III) chloride (Fe-PhenTPy), was synthesized as a new mediator for the NAD-GDH system. Due to the high oxidation potential of the mediator, the detection potential was tuned to be more closely fitted toward the enzyme reaction potential, less than 400 mV (vs. Ag/AgCl), by mixing with an additional iron mediator. The impedance spectrometry for the enzyme sensor containing the mixed mediators showed an enhanced charge transfer property. In addition, a new cartridge-type glucose meter was manufactured using effective aligned-electrodes, which showed an enhanced response compared with conventional electrode alignment. The proposed glucose sensor resulted in a wide dynamic range in the concentration range of 30 - 500 mg dL(-1) with a reduced interference effect and a good sensitivity of 0.57 μA mM(-1).

  11. Crimes Scenes as Augmented Reality, off-screen, online and offline

    DEFF Research Database (Denmark)

    Sandvik, Kjetil; Waade, Anne Marit

    2008-01-01

    Our field of investigation is site specific realism in crime fiction and spatial production as media specific features. We analyze the (re)production of crime scenes in respectively crime series, computer games and tourist practice, and relate this to the ideas of augmented reality. Using...... a distinction between places as locations situated in the physical world and spaces as imagined or virtual locations as our point of departure, this paper investigates how places in various ways have become augmented by means of mediatization. Augmented reality represents processes of mediatization that broaden...... and enhance spatial experiences. These processes are characterized by the activation of users and the creation of artificial operational environments embedded in various physical or virtual locations. The idea of augmented spatial practice is related to the ideas of site specific aesthetic...

  12. Crimes Scenes as Augmented Reality, off-screen, online and offline

    DEFF Research Database (Denmark)

    Sandvik, Kjetil; Waade, Anne-Marit

    Our field of investigation is site specific realism in crime fiction and spatial production as media specific features. We analyze the (re)production of crime scenes in respectively crime series, computer games and tourist practice, and relate this to the ideas of augmented reality. Using...... a distinction between places as locations situated in the physical world and spaces as imagined or virtual locations as our point of departure, this paper investigates how places in various ways have become augmented by means of mediatization. Augmented reality represents processes of mediatization that broaden...... and enhance spatial experiences. These processes are characterized by the activation of users and the creation of artificial operational environments embedded in various physical or virtual locations. The idea of augmented spatial practice is related to the ideas of site specific aesthetic...

  13. Augmented Reality in Science Education

    DEFF Research Database (Denmark)

    Nielsen, Birgitte Lund; Brandt, Harald; Swensen, Hakon

    Augmented reality (AR) holds great promise as a learning tool. However, most extant studies in this field have focused on the technology itself. The poster presents findings from the first stage of the AR-sci project addressing the issue of applying AR for educational purposes. Benefits...

  14. Augmented Reality in Science Education

    DEFF Research Database (Denmark)

    Nielsen, Birgitte Lund; Brandt, Harald; Swenson, Hakon

    2015-01-01

    Augmented reality (AR) holds great promise as a learning tool. However, most extant studies in this field have focused on the technology itself. The poster presents findings from the first stage of the AR-sci project addressing the issue of applying AR for educational purposes. Benefits...

  15. Indeterminacy and labor augmenting externalities

    DEFF Research Database (Denmark)

    Poulsen, Odile; Goenka, Aditya

    2002-01-01

    In this two-sector discrete time model of endogenous economic growth intersectoral effects are assumed to be "labor augmenting" We derive necessary and sufficient conditions for local indeterminacy and multiplicity of the balanced growth path in terms of factor intensities in both sectors...

  16. Flavonoids have differential effects on glucose absorption in rats (Rattus norvegicus) and American robins (Turdis migratorius).

    Science.gov (United States)

    Skopec, Michele M; Green, Adam K; Karasov, William H

    2010-02-01

    Mounting evidence suggests that small birds rely largely on non-mediated intestinal absorption of glucose through the paracellular pathway, while non-flying mammals rely on mediated absorption across the enterocyte membranes by using glucose transporters SGLT-1 and GLUT-2. Relying on non-mediated transport of glucose may decrease its absorption rate at low glucose concentrations but may release small birds from the effects of glucose transport inhibitors. We evaluated transport by using flavonoids known to inhibit glucose transport in vitro. Quercetin, isoquercetrin, and phloridzin were tested in rats (Rattus norvegicus) and robins (Turdis migratirius), and naringenin, naringenin-7-glucoside, genistein, epigallocatechin gallate (EGCG), and phloretin were used only in rats. By using a pharmacokinetic approach that involves serial blood collection and area under the curve calculations, we determined the bioavailability of 3-0-methyl D-glucose, the non-metabolized analogue of D-glucose. Six of the eight flavonoids tested in rats significantly decreased the absorption of 3-0-methyl D-glucose, while none of the flavonoids tested in robins significantly decreased the bioavailability of 3-0-methyl D-glucose. We conclude that flavonoids effectively decrease glucose absorption in rats, which rely on mediated absorption of glucose, but that flavonoids do not have an effect in robins, which rely on non-mediated absorption of glucose.

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  18. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  19. Glucose-6-phosphate dehydrogenase

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003671.htm Glucose-6-phosphate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) is a protein that helps red ...

  20. Your Glucose Meter

    Science.gov (United States)

    ... Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco ... Tips for Testing Your Blood Sugar and Caring for Your Meter Glucose meters test and record how much sugar (called glucose) is in your ...

  1. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high blood glucose (blood sugar). High blood glucose happens when the body has too little insulin or when the body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: ...

  2. Interleukin-1 beta-induced nitric oxide production from isolated rat islets is modulated by D-glucose and 3-isobutyl-1-methyl xanthine

    DEFF Research Database (Denmark)

    Andersen, H U; Mauricio, D; Karlsen, Allan Ertman

    1996-01-01

    Interleukin-1 beta has been proposed to cause selective beta-cell destruction via the induction of nitric oxide synthesis. The cytotoxic effect of interleukin-1 beta is modulated by the concentration of D-glucose in the medium. The aim of this study was to investigate if D-glucose-mediated modula......Interleukin-1 beta has been proposed to cause selective beta-cell destruction via the induction of nitric oxide synthesis. The cytotoxic effect of interleukin-1 beta is modulated by the concentration of D-glucose in the medium. The aim of this study was to investigate if D...... effects on acute insulin release was found at high (28 mmol/l) concentrations of D-glucose, and blocking nitrite production by the L-arginine analog aminoguanidine, which selectively inhibits the cytokine-inducible nitric oxide synthase, did not result in protection against the inhibitory action...... that could be reproduced by the cAMP analog dibutyryl cAMP. Addition of 3-isobutyl-1-methyl xanthine resulted in a threefold reduction in the mRNA level of interleukin-1 beta-induced inducible nitric oxide synthase. We conclude that interleukin-1 beta-induced islet nitric oxide synthesis is augmented by D...

  3. High glucose upregulates BACE1-mediated Aβ production through ROS-dependent HIF-1α and LXRα/ABCA1-regulated lipid raft reorganization in SK-N-MC cells.

    Science.gov (United States)

    Lee, Hyun Jik; Ryu, Jung Min; Jung, Young Hyun; Lee, Sei-Jung; Kim, Jeong Yeon; Lee, Sang Hun; Hwang, In Koo; Seong, Je Kyung; Han, Ho Jae

    2016-11-10

    There is an accumulation of evidence indicating that the risk of Alzheimer's disease is associated with diabetes mellitus, an indicator of high glucose concentrations in blood plasma. This study investigated the effect of high glucose on BACE1 expression and amyloidogenesis in vivo, and we present details of the mechanism associated with those effects. Our results, using ZLC and ZDF rat models, showed that ZDF rats have high levels of amyloid-beta (Aβ), phosphorylated tau, BACE1, and APP-C99. In vitro result with mouse hippocampal neuron and SK-N-MC, high glucose stimulated Aβ secretion and apoptosis in a dose-dependent manner. In addition, high glucose increased BACE1 and APP-C99 expressions, which were reversed by a reactive oxygen species (ROS) scavenger. Indeed, high glucose increased intracellular ROS levels and HIF-1α expression, associated with regulation of BACE1 and Liver X Receptor α (LXRα). In addition, high glucose induced ATP-binding cassette transporter A1 (ABCA1) down-regulation, was associated with LXR-induced lipid raft reorganization and BACE1 localization on the lipid raft. Furthermore, silencing of BACE1 expression was shown to regulate Aβ secretion and apoptosis of SK-N-MC. In conclusion, high glucose upregulates BACE1 expression and activity through HIF-1α and LXRα/ABCA1-regulated lipid raft reorganization, leading to Aβ production and apoptosis of SK-N-MC.

  4. Use of Augmented Reality in Education

    OpenAIRE

    Jeřábek, Tomáš

    2014-01-01

    This thesis deals with phenomena of augmented reality in context of didactics. The thesis aims to define augmented reality in conceptual and content area and focuses on augmented reality in the structure of educational tools and identification of its functions and use from the didactical standpoint. The thesis characterizes augmented reality as a specific technological-perceptual concept and establishes a system of perceptual, technological and resulting aspects that reflect important paramet...

  5. Identification of Glucose Transporters in Aspergillus nidulans

    Science.gov (United States)

    dos Reis, Thaila Fernanda; Menino, João Filipe; Bom, Vinícius Leite Pedro; Brown, Neil Andrew; Colabardini, Ana Cristina; Savoldi, Marcela; Goldman, Maria Helena S.; Rodrigues, Fernando; Goldman, Gustavo Henrique

    2013-01-01

    To characterize the mechanisms involved in glucose transport, in the filamentous fungus Aspergillus nidulans, we have identified four glucose transporter encoding genes hxtB-E. We evaluated the ability of hxtB-E to functionally complement the Saccharomyces cerevisiae EBY.VW4000 strain that is unable to grow on glucose, fructose, mannose or galactose as single carbon source. In S. cerevisiae HxtB-E were targeted to the plasma membrane. The expression of HxtB, HxtC and HxtE was able to restore growth on glucose, fructose, mannose or galactose, indicating that these transporters accept multiple sugars as a substrate through an energy dependent process. A tenfold excess of unlabeled maltose, galactose, fructose, and mannose were able to inhibit glucose uptake to different levels (50 to 80 %) in these s. cerevisiae complemented strains. Moreover, experiments with cyanide-m-chlorophenylhydrazone (CCCP), strongly suggest that hxtB, -C, and –E mediate glucose transport via active proton symport. The A. nidulans ΔhxtB, ΔhxtC or ΔhxtE null mutants showed ~2.5-fold reduction in the affinity for glucose, while ΔhxtB and -C also showed a 2-fold reduction in the capacity for glucose uptake. The ΔhxtD mutant had a 7.8-fold reduction in affinity, but a 3-fold increase in the capacity for glucose uptake. However, only the ΔhxtB mutant strain showed a detectable decreased rate of glucose consumption at low concentrations and an increased resistance to 2-deoxyglucose. PMID:24282591

  6. Augmented Reality for Multi-disciplinary Collaboration

    OpenAIRE

    WANG, XIANGYU; Rui

    2010-01-01

    This chapter presents a framework for multi-disciplinary collaboration. Tangible Augmented Reality has been raised as one of suitable systems for design collaboration. Furthermore, it emphasizes the advantages of Tangible Augmented Reality to illustrate the needs for integrating the Tangible User Interfaces and Augmented Reality Systems.

  7. The Strategic Mediator

    DEFF Research Database (Denmark)

    Rossignoli, Cecilia; Carugati, Andrea; Mola, Lapo

    2009-01-01

    The last 10 years have witnessed the emergence of electronic marketplaces as players that leverage new technologies to facilitate B2B internet-mediated collaborative business. Nowadays these players are augmenting their services from simple intermediation to include new inter-organizational relat......The last 10 years have witnessed the emergence of electronic marketplaces as players that leverage new technologies to facilitate B2B internet-mediated collaborative business. Nowadays these players are augmenting their services from simple intermediation to include new inter......-marketplace assumes the paradoxical role of strategic mediator: an agent who upholds and heightens the fences of the transactions instead of leveling them. The results have implication in shaping how we see the role of technology as strategic or commoditized....

  8. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.

    Science.gov (United States)

    Merovci, Aurora; Solis-Herrera, Carolina; Daniele, Giuseppe; Eldor, Roy; Fiorentino, Teresa Vanessa; Tripathy, Devjit; Xiong, Juan; Perez, Zandra; Norton, Luke; Abdul-Ghani, Muhammad A; DeFronzo, Ralph A

    2014-02-01

    Chronic hyperglycemia impairs insulin action, resulting in glucotoxicity, which can be ameliorated in animal models by inducing glucosuria with renal glucose transport inhibitors. Here, we examined whether reduction of plasma glucose with a sodium-glucose cotransporter 2 (SGLT2) inhibitor could improve insulin-mediated tissue glucose disposal in patients with type 2 diabetes. Eighteen diabetic men were randomized to receive either dapagliflozin (n = 12) or placebo (n = 6) for 2 weeks. We measured insulin-mediated whole body glucose uptake and endogenous glucose production (EGP) at baseline and 2 weeks after treatment using the euglycemic hyperinsulinemic clamp technique. Dapagliflozin treatment induced glucosuria and markedly lowered fasting plasma glucose. Insulin-mediated tissue glucose disposal increased by approximately 18% after 2 weeks of dapagliflozin treatment, while placebo-treated subjects had no change in insulin sensitivity. Surprisingly, following dapagliflozin treatment, EGP increased substantially and was accompanied by an increase in fasting plasma glucagon concentration. Together, our data indicate that reduction of plasma glucose with an agent that works specifically on the kidney to induce glucosuria improves muscle insulin sensitivity. However, glucosuria induction following SGLT2 inhibition is associated with a paradoxical increase in EGP. These results provide support for the glucotoxicity hypothesis, which suggests that chronic hyperglycemia impairs insulin action in individuals with type 2 diabetes.

  9. [Glucose Metabolism: Stress Hyperglycemia and Glucose Control].

    Science.gov (United States)

    Tanaka, Katsuya; Tsutsumi, Yasuo M

    2016-05-01

    It is important for the anesthesiologists to understand pathophysiology of perioperative stress hyperglycemia, because it offers strategies for treatment of stress hyperglycemia. The effect of glucose tolerance is different in the choice of the anesthetic agent used in daily clinical setting. Specifically, the volatile anesthetics inhibit insulin secretion after glucose load and affects glucose tolerance. During minor surgery by the remifentanil anesthesia, the stress reaction is hard to be induced, suggesting that we should consider low-dose glucose load. Finally it is necessary to perform the glycemic control of the patients who fell into stress hyperglycemia depending on the individual patient. However, there are a lot of questions to be answered in the future. The prognosis of the perioperative patients is more likely to be greatly improved if we can control stress hyperglycemia.

  10. Measuring patient outcomes in breast augmentation: introducing the BREAST-Q Augmentation module.

    Science.gov (United States)

    Pusic, Andrea L; Reavey, Patrick L; Klassen, Anne F; Scott, Amie; McCarthy, Colleen; Cano, Stefan J

    2009-01-01

    The Breast-Q Augmentation module is a new and unique questionnaire for measuring patient-reported outcomes following breast augmentation. It has undergone a rigorous development and validation process and is currently the only questionnaire for breast augmentation that meets international and federal standards for questionnaire development. The Breast-Q Augmentation module covers a comprehensive set of concerns of breast augmentation patients, including satisfaction with breasts and impact on quality of life. With its excellent psychometric properties, the Breast-Q Augmentation module can provide clinicians and researchers with a wealth of essential data to improve the field of breast augmentation from the perspectives of both surgeons and patients.

  11. Augmented reality building operations tool

    Energy Technology Data Exchange (ETDEWEB)

    Brackney, Larry J.

    2014-09-09

    A method (700) for providing an augmented reality operations tool to a mobile client (642) positioned in a building (604). The method (700) includes, with a server (660), receiving (720) from the client (642) an augmented reality request for building system equipment (612) managed by an energy management system (EMS) (620). The method (700) includes transmitting (740) a data request for the equipment (612) to the EMS (620) and receiving (750) building management data (634) for the equipment (612). The method (700) includes generating (760) an overlay (656) with an object created based on the building management data (634), which may be sensor data, diagnostic procedures, or the like. The overlay (656) is configured for concurrent display on a display screen (652) of the client (642) with a real-time image of the building equipment (612). The method (700) includes transmitting (770) the overlay (656) to the client (642).

  12. Effective Augmentation of Complex Networks

    Science.gov (United States)

    Wang, Jinjian; Yu, Xinghuo; Stone, Lewi

    2016-05-01

    Networks science plays an enormous role in many aspects of modern society from distributing electrical power across nations to spreading information and social networking amongst global populations. While modern networks constantly change in size, few studies have sought methods for the difficult task of optimising this growth. Here we study theoretical requirements for augmenting networks by adding source or sink nodes, without requiring additional driver-nodes to accommodate the change i.e., conserving structural controllability. Our “effective augmentation” algorithm takes advantage of clusters intrinsic to the network topology, and permits rapidly and efficient augmentation of a large number of nodes in one time-step. “Effective augmentation” is shown to work successfully on a wide range of model and real networks. The method has numerous applications (e.g. study of biological, social, power and technological networks) and potentially of significant practical and economic value.

  13. Glucose utilization rates regulate intake levels of artificial sweeteners.

    Science.gov (United States)

    Tellez, Luis A; Ren, Xueying; Han, Wenfei; Medina, Sara; Ferreira, Jozélia G; Yeckel, Catherine W; de Araujo, Ivan E

    2013-11-15

    It is well established that animals including humans attribute greater reinforcing value to glucose-containing sugars compared to their non-caloric counterparts, generally termed 'artificial sweeteners'. However, much remains to be determined regarding the physiological signals and brain systems mediating the attribution of greater reinforcing value to sweet solutions that contain glucose. Here we show that disruption of glucose utilization in mice produces an enduring inhibitory effect on artificial sweetener intake, an effect that did not depend on sweetness perception or aversion. Indeed, such an effect was not observed in mice presented with a less palatable, yet caloric, glucose solution. Consistently, hungry mice shifted their preferences away from artificial sweeteners and in favour of glucose after experiencing glucose in a hungry state. Glucose intake was found to produce significantly greater levels of dopamine efflux compared to artificial sweetener in dorsal striatum, whereas disrupting glucose oxidation suppressed dorsal striatum dopamine efflux. Conversely, inhibiting striatal dopamine receptor signalling during glucose intake in sweet-naïve animals resulted in reduced, artificial sweetener-like intake of glucose during subsequent gluco-deprivation. Our results demonstrate that glucose oxidation controls intake levels of sweet tastants by modulating extracellular dopamine levels in dorsal striatum, and suggest that glucose utilization is one critical physiological signal involved in the control of goal-directed sweetener intake.

  14. Augmented oxygen-mediated transcriptional activation of cytochrome P450 (CYP)1A expression and increased susceptibilities to hyperoxic lung injury in transgenic mice carrying the human CYP1A1 or mouse 1A2 promoter in vivo.

    Science.gov (United States)

    Jiang, Weiwu; Couroucli, Xanthi I; Wang, Lihua; Barrios, Roberto; Moorthy, Bhagavatula

    2011-04-01

    Supplemental oxygen administration is frequently administered to pre-term and term infants having pulmonary insufficiency. However, hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. Cytochrome P450 (CYP)A enzymes have been implicated in hyperoxic lung injury. In this study, we tested the hypothesis that hyperoxia induces CYP1A1 and 1A2 enzymes by transcriptional activation of the corresponding promoters in vivo, and transgenic mice expressing the human CYP1A1 or the mouse 1A2 promoter would be more susceptible to hyperoxic lung injury than wild type (WT) mice. Adult WT (CD-1) (12week-old) mice, transgenic mice carrying a 10kb human CYP1A1 promoter and the luciferase (luc) reporter gene (CYP1A1-luc), or mice expressing the mouse CYP1A2 promoter (CYP1A2-luc) were maintained in room air or exposed to hyperoxia for 24-72h. Hyperoxia exposure of CYP1A1-luc mice for 24 and 48h resulted in 2.5- and 1.25-fold increases, respectively, in signal intensities, compared to room air controls. By 72h, the induction had declined to control levels. CYP1A2-luc mice also showed enhanced luc expression after 24-48h, albeit to a lesser extent than those expressing the CYP1A1 promoter. Also, these mice showed decreased levels of endogenous CYP1A1 and 1A2 expression after prolonged hyperoxia, and were also more susceptible to lung injury than similarly exposed WT mice, with CYP1A2-luc mice showing the greatest injury. Our results support the hypothesis that hyperoxia induces CYP1A enzymes by transcriptional activation of its corresponding promoters, and that decreased endogenous expression of these enzymes contribute to the increased susceptibilities to hyperoxic lung injury in the transgenic animals. In summary, this is the first report providing direct evidence of hyperoxia-mediated induction of CYP1A1 and CYP1A2 expression in vivo by mechanisms entailing transcriptional activation of the corresponding promoters, a phenomenon that has

  15. Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction – A model for cross-modulation

    Directory of Open Access Journals (Sweden)

    Thompson Erik W

    2009-07-01

    Full Text Available Abstract Background A feature of epithelial to mesenchymal transition (EMT relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC. Methods PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1 and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome. Results When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4 and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4. Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse

  16. Dorsal Augmentation with Septal Cartilage

    OpenAIRE

    Murrell, George L.

    2008-01-01

    Deficiency of nasal dorsal projection may be inherent or acquired. Repair is most commonly performed with an onlay graft. When nasal septal cartilage is available, it is the author's preferred source for graft material. It is important to realize that dorsal augmentation is an operation performed for aesthetic not functional reasons. As such, patients understandably scrutinize their postoperative result, and attention to detail in all aspects of the surgery is critical in achieving a favorabl...

  17. Psychotherapy Augmentation through Preconscious Priming

    OpenAIRE

    Borgeat, François; O’Connor, Kieron; Amado, Danielle; St-Pierre-Delorme, Marie-Ève

    2013-01-01

    Objective: To test the hypothesis that repeated preconscious (masked) priming of personalized positive cognitions could augment cognitive change and facilitate achievement of patients’ goals following a therapy. Methods: Twenty social phobic patients (13 women) completed a 36-weeks study beginning by 12 weeks of group behavioral therapy. After the therapy, they received 6 weeks of preconscious priming and 6 weeks of a control procedure in a randomized cross-over design. The Priming conditi...

  18. Radiation/Catalytic Augmented Combustion.

    Science.gov (United States)

    1980-09-01

    NATIO& NAk H(fJI At tl TANUAHTOb 19 A ~omm.81-0287 LVL RADIATION/CATALYTIC AUGMENTED COMBUST ION MOSHE LAVID CORPORATE RESEARCH-TECHNOLOGY FEASIBILITY...refinements as necessary. i. Perform cannular combustor experiments to Investigate ignition and flame attachment in flowing, liquid -fuel, unpremixed...stabilizer, with a sintered metal disk on the downstream side through which hot gases or products of partial fuel oxidation can be passed. Experimental

  19. Media-Augmented Exercise Machines

    Science.gov (United States)

    Krueger, T.

    2002-01-01

    Cardio-vascular exercise has been used to mitigate the muscle and cardiac atrophy associated with adaptation to micro-gravity environments. Several hours per day may be required. In confined spaces and long duration missions this kind of exercise is inevitably repetitive and rapidly becomes uninteresting. At the same time, there are pressures to accomplish as much as possible given the cost- per-hour for humans occupying orbiting or interplanetary. Media augmentation provides a the means to overlap activities in time by supplementing the exercise with social, recreational, training or collaborative activities and thereby reducing time pressures. In addition, the machine functions as an interface to a wide range of digital environments allowing for spatial variety in an otherwise confined environment. We hypothesize that the adoption of media augmented exercise machines will have a positive effect on psycho-social well-being on long duration missions. By organizing and supplementing exercise machines, data acquisition hardware, computers and displays into an interacting system this proposal increases functionality with limited additional mass. This paper reviews preliminary work on a project to augment exercise equipment in a manner that addresses these issues and at the same time opens possibilities for additional benefits. A testbed augmented exercise machine uses a specialty built cycle trainer as both input to a virtual environment and as an output device from it using spatialized sound, and visual displays, vibration transducers and variable resistance. The resulting interactivity increases a sense of engagement in the exercise, provides a rich experience of the digital environments. Activities in the virtual environment and accompanying physiological and psychological indicators may be correlated to track and evaluate the health of the crew.

  20. Photon management for augmented photosynthesis

    Science.gov (United States)

    Ooms, Matthew D.; Dinh, Cao Thang; Sargent, Edward H.; Sinton, David

    2016-09-01

    Microalgae and cyanobacteria are some of nature's finest examples of solar energy conversion systems, effortlessly transforming inorganic carbon into complex molecules through photosynthesis. The efficiency of energy-dense hydrocarbon production by photosynthetic organisms is determined in part by the light collected by the microorganisms. Therefore, optical engineering has the potential to increase the productivity of algae cultivation systems used for industrial-scale biofuel synthesis. Herein, we explore and report emerging and promising material science and engineering innovations for augmenting microalgal photosynthesis.

  1. Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice

    DEFF Research Database (Denmark)

    Gunnarsson, P Thomas; Winzell, Maria Sörhede; Deacon, Carolyn F

    2006-01-01

    -1 (GLP-1). To explore this, we examined the release and inactivation of GIP and GLP-1 after administration of glucose with or without OA or WP through gastric gavage in anesthetized C57BL/6J mice. Insulin responses to glucose (75 mg) were 3-fold augmented by addition of WP (75 mg; P

  2. 抗癌药SN38通过脂筏促进Fas介导的细胞凋亡%Anti-cancer drug SN 38, augments FAS-mediated apoptosis through lipid raft

    Institute of Scientific and Technical Information of China (English)

    曹妍; 王大南; 孙玥; 梅原久範; 吕昌龙

    2012-01-01

    Objective:To investigate the mechanisms of anti-cancer drug, SN38, on Fas-mediated apoptosis and to study the role of lipid raft in such progress. Methods: WR/FAS-SM (-) cells and WR/FAS-SMS1 cells were treated by SN38 and/or CH11. DNA damage-associated moleculars and caspase were studied for further investigation for activation level and characteristics of such mo-leculars by Western blot. Results: Combination of SN38 and CH11 could induce the activation of ATM-Chkl -p53 pathway and caspase-3,8 in WR/Fas-SMSl cells and the inactivation of p21. Whereas the activation of Chkl-p53 and caspase-3,8 did not induce the inacti-vation of p21 in WR/Fas-SM(-) cells. Conclusion;The stronger apoptosis in WR/Fas-SMSl cells induced by the combination of SN38 and CH11 was caused by the activation of ATM-Chkl-p53 pathway and caspase-3,8 and the inactivation of p21. Lipid raft induced stronger apoptosis in WR/Fas-SMSl cells than in WR/Fas-SM(-) cells by decreasing the expression of phospho-p21 with the treatment of SN38 and CH11.%目的:探讨抗癌药SN38对Fas介导凋亡的影响机制,并进一步探讨脂筏在该过程的作用.方法:单独或者联合应用SN38和CH11(Fas抗体)作用于脂筏阴性和脂筏阳性的细胞株WR/FAS-SM(-)细胞和WR/FAS-SMS1细胞,通过Western blot的方法检测细胞内部DNA损伤的信号分子以及caspase分子的活化情况,并分析它们的活化强度和作用特点.结果:在SN38和CH11的共同作用下,WR/FAS-SMS1细胞ATM-Chk1-p53途径及caspase-3.8活化,p21活化水平降低,而WR/FAS-SM(-)细胞的Chk1-p53途径以及caspase-3.8活化,而p21活化水平则未见降低.结论:SN38和CH11的共同应用与SN38单独应用相比,通过活化ATM-Chk1-p53途径,导致p21活化水平降低,进而活化caspase-3,8,从而促进WR/Fas-SMS1细胞的凋亡;该过程中脂筏可能通过调控p21的不同活化状态最终导致了WR/FAS-SM(-)细胞和WR/FAS-SMS1细胞间凋亡率的差异.

  3. Effect of adrenaline on glucose kinetics during exercise in adrenalectomised humans

    DEFF Research Database (Denmark)

    Howlett, K; Galbo, H; Lorentsen, J

    1999-01-01

    1. The role of adrenaline in regulating hepatic glucose production and muscle glucose uptake during exercise was examined in six adrenaline-deficient, bilaterally adrenalectomised humans. Six sex- and age-matched healthy individuals served as controls (CON). 2. Adrenalectomised subjects cycled...... for 45 min at 68 +/- 1 % maximum pulmonary O2 uptake (VO2,max), followed by 15 min at 84 +/- 2 % VO2, max without (-ADR) or with (+ADR) adrenaline infusion, which elevated plasma adrenaline levels (45 min, 4.49 +/- 0.69 nmol l-1; 60 min, 12.41 +/- 1.80 nmol l-1; means +/- s.e.m.). Glucose kinetics were...... measured using [3-3H]glucose. 3. Euglycaemia was maintained during exercise in CON and -ADR, whilst in +ADR plasma glucose was elevated. The exercise-induced increase in hepatic glucose production was similar in +ADR and -ADR; however, adrenaline infusion augmented the rise in hepatic glucose production...

  4. Effect of adrenaline on glucose kinetics during exercise in adrenalectomised humans

    DEFF Research Database (Denmark)

    Howlett, K; Galbo, H; Lorentsen, J;

    1999-01-01

    trials. Adrenaline infusion suppressed growth hormone and elevated plasma free fatty acids, glycerol and lactate. Alanine and beta-hydroxybutyrate levels were similar between trials. 5. The results demonstrate that glucose homeostasis was maintained during exercise in adrenalectomised subjects......1. The role of adrenaline in regulating hepatic glucose production and muscle glucose uptake during exercise was examined in six adrenaline-deficient, bilaterally adrenalectomised humans. Six sex- and age-matched healthy individuals served as controls (CON). 2. Adrenalectomised subjects cycled...... measured using [3-3H]glucose. 3. Euglycaemia was maintained during exercise in CON and -ADR, whilst in +ADR plasma glucose was elevated. The exercise-induced increase in hepatic glucose production was similar in +ADR and -ADR; however, adrenaline infusion augmented the rise in hepatic glucose production...

  5. Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat.

    Science.gov (United States)

    Pulsinelli, W A; Waldman, S; Rawlinson, D; Plum, F

    1982-11-01

    We compared the effects of glucose injection with those of saline or mannitol on ischemic brain damage and brain water content in a four-vessel occlusion (4-VO) rat model, which simultaneously causes severe forebrain ischemia and moderate hindbrain ischemia. Glucose given before onset of ischemia was followed by severe brain injury, with necrosis of the majority of neocortical neurons and glia, substantial neuronal damage throughout the remainder of forebrain, and severe brain edema. By comparison, saline injection before forebrain ischemia resulted in only scattered ischemic damage confined to neurons and no change in the brain water content. Mannitol injection before 4-VO or D-glucose injection during or after 4-VO produced no greater forebrain damage than did the saline injection. Morphologic damage in the cerebellum, however, was increased by D-glucose injection given either before or during 4-VO. The results demonstrate that hyperglycemia before severe brain ischemia or during moderate ischemia markedly augments morphologic brain damage.

  6. Biostable glucose permeable polymer

    DEFF Research Database (Denmark)

    2017-01-01

    A new biostable glucose permeable polymer has been developed which is useful, for example, in implantable glucose sensors. This biostable glucose permeable polymer has a number of advantageous characteristics and, for example, does not undergo hydrolytic cleavage and degradation, thereby providing...... a composition that facilitates long term sensor stability in vivo. The versatile characteristics of this polymer allow it to be used in a variety of contexts, for example to form the body of an implantable glucose sensor. The invention includes the polymer composition, sensor systems formed from this polymer...

  7. Blood Glucose Levels

    Directory of Open Access Journals (Sweden)

    Carlos Estela

    2011-01-01

    Full Text Available The purpose of this study was to establish a mathematical model which can be used to estimate glucose levels in the blood over time. The equations governing this process were manipulated with the use of techniques such as separation of variables and integration of first order differential equations, which resulted in a function that described the glucose concentration in terms of time. This function was then plotted, which allowed us to find when glucose concentration was at its highest. The model was then used to analyze two cases where the maximum glucose level could not exceed a certain level while the amount of carbohydrates and glycemic index were varied, independently.

  8. Augmented reality in intraventricular neuroendoscopy.

    Science.gov (United States)

    Finger, T; Schaumann, A; Schulz, M; Thomale, Ulrich-W

    2017-06-01

    Individual planning of the entry point and the use of navigation has become more relevant in intraventricular neuroendoscopy. Navigated neuroendoscopic solutions are continuously improving. We describe experimentally measured accuracy and our first experience with augmented reality-enhanced navigated neuroendoscopy for intraventricular pathologies. Augmented reality-enhanced navigated endoscopy was tested for accuracy in an experimental setting. Therefore, a 3D-printed head model with a right parietal lesion was scanned with a thin-sliced computer tomography. Segmentation of the tumor lesion was performed using Scopis NovaPlan navigation software. An optical reference matrix is used to register the neuroendoscope's geometry and its field of view. The pre-planned ROI and trajectory are superimposed in the endoscopic image. The accuracy of the superimposed contour fitting on endoscopically visualized lesion was acquired by measuring the deviation of both midpoints to one another. The technique was subsequently used in 29 cases with CSF circulation pathologies. Navigation planning included defining the entry points, regions of interests and trajectories, superimposed as augmented reality on the endoscopic video screen during intervention. Patients were evaluated for postoperative imaging, reoperations, and possible complications. The experimental setup revealed a deviation of the ROI's midpoint from the real target by 1.2 ± 0.4 mm. The clinical study included 18 cyst fenestrations, ten biopsies, seven endoscopic third ventriculostomies, six stent placements, and two shunt implantations, being eventually combined in some patients. In cases of cyst fenestrations postoperatively, the cyst volume was significantly reduced in all patients by mean of 47%. In biopsies, the diagnostic yield was 100%. Reoperations during a follow-up period of 11.4 ± 10.2 months were necessary in two cases. Complications included one postoperative hygroma and one insufficient

  9. Digital Illumination for Augmented Studios

    Directory of Open Access Journals (Sweden)

    Stefanie Zollmann

    2006-12-01

    Full Text Available Virtual studio technology plays an important role for modern television productions. Blue-screen matting is a common technique for integrating real actors or moderators into computer generated sceneries. Augmented reality offers the possibility to mix real and virtual in a more general context. This article proposes a new technological approach for combining real studio content with computer-generated information. Digital light projection allows a controlled spatial, temporal, chrominance and luminance modulation of illumination opening new possibilities for TV studios.

  10. Webizing mobile augmented reality content

    Science.gov (United States)

    Ahn, Sangchul; Ko, Heedong; Yoo, Byounghyun

    2014-01-01

    This paper presents a content structure for building mobile augmented reality (AR) applications in HTML5 to achieve a clean separation of the mobile AR content and the application logic for scaling as on the Web. We propose that the content structure contains the physical world as well as virtual assets for mobile AR applications as document object model (DOM) elements and that their behaviour and user interactions are controlled through DOM events by representing objects and places with a uniform resource identifier. Our content structure enables mobile AR applications to be seamlessly developed as normal HTML documents under the current Web eco-system.

  11. The glucose oxidase-peroxidase assay for glucose

    Science.gov (United States)

    The glucose oxidase-peroxidase assay for glucose has served as a very specific, sensitive, and repeatable assay for detection of glucose in biological samples. It has been used successfully for analysis of glucose in samples from blood and urine, to analysis of glucose released from starch or glycog...

  12. Adipocyte JAK2 mediates growth hormone–induced hepatic insulin resistance

    Science.gov (United States)

    Corbit, Kevin C.; Camporez, João Paulo G.; Tran, Jennifer L.; Wilson, Camella G.; Lowe, Dylan A.; Nordstrom, Sarah M.; Ganeshan, Kirthana; Perry, Rachel J.; Weiss, Ethan J.

    2017-01-01

    For nearly 100 years, growth hormone (GH) has been known to affect insulin sensitivity and risk of diabetes. However, the tissue governing the effects of GH signaling on insulin and glucose homeostasis remains unknown. Excess GH reduces fat mass and insulin sensitivity. Conversely, GH insensitivity (GHI) is associated with increased adiposity, augmented insulin sensitivity, and protection from diabetes. Here, we induce adipocyte-specific GHI through conditional deletion of Jak2 (JAK2A), an obligate transducer of GH signaling. Similar to whole-body GHI, JAK2A mice had increased adiposity and extreme insulin sensitivity. Loss of adipocyte Jak2 augmented hepatic insulin sensitivity and conferred resistance to diet-induced metabolic stress without overt changes in circulating fatty acids. While GH injections induced hepatic insulin resistance in control mice, the diabetogenic action was absent in JAK2A mice. Adipocyte GH signaling directly impinged on both adipose and hepatic insulin signal transduction. Collectively, our results show that adipose tissue governs the effects of GH on insulin and glucose homeostasis. Further, we show that JAK2 mediates liver insulin sensitivity via an extrahepatic, adipose tissue–dependent mechanism. PMID:28194444

  13. Enhancive effects of D-glucose and its analogs on expression of d-glucose-unrelated transgenes in mammalian cells.

    Science.gov (United States)

    Kimura, Miyuki; Namba, Hikaru; Okubo, Manabu; Ezumi, Mai; Susumu, Nao; Yamada, Masao; Arao, Yujiro

    2011-08-01

    We studied the effects of d-glucose on transgene expression in mammalian cells by a reporter gene assay using CV-1 cells and a CMV promoter-controlled EGFP gene. Treatment of CV-1 cells with 5% D-glucose unchanged the number of fluorescent cells in fluorescence microscopic observation but significantly intensified fluorescence in the fluorometric assay. Furthermore, EGFP itself and mRNA became more abundant in Western blot and quantitative RT-PCR analyses of 5% D-glucose-treated cells, respectively. These results indicate that elevated D-glucose can activate transgene expression via transcriptional stimulation, at least in part. The same concentrations of L-glucose led to only negligible increases in transgene expression, indicating that D-glucose's effect is different from its osmotic effect. The D-glucose-induced augmentation of fluorescence was observed not only in the experiment using the CMV promoter-controlled EGFP gene but also in experiments using the SV40 and RSV promoter-controlled ones, suggesting that elevated D-glucose can enhance transgene expression regulated by various promoters commonly used in transgene expression. The assessment of D-glucose analogs for their enhancive effects on transgene expression revealed that 1,6-anhydro-D-glucose and β-methyl-D-glucoside had stronger effects than D-glucose. From this result, we can expect to find more effective carbohydrates to enhance transgene expression. The α- and β-M-D-glucosides, which are slightly different from each other in three-dimensional structure, exerted largely distinct stimulative effects on transgene expression, suggesting that fundamental rules determine the enhancive effects of saccharides and that the modification of the saccharide by applying such rules will enable us to develop more powerful substances for transgene expression. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. Augmented Plasma Adiponectin after Prolonged Fasting During Ramadan in Men

    Directory of Open Access Journals (Sweden)

    Sadegh Feizollahzadeh

    2014-07-01

    Full Text Available Background: Intermittent fasting during Ramadan entails major changes in metabolism and energy expenditure. This study sought to determine effect of the Ramadan fasting on serum levels of adiponectin and tumor necrosis factor-α (TNF-α as two inter-related peptides involved in cells sensitivity to insulin and glucose metabolism. Methods: Total of seventy healthy men, with age range equal or greater than 30, with at least three type2 diabetes mellitus (DM risk factors were selected. Serum lipid profile, anthropometric indices and plasma glucose levels were determined using conventional methods. Also, serum adiponectin and TNF- α concentrations were assessed using Enzyme-linked Immunosorbent Assay. Data were analyzed by paired t-test. Results: Ramadan fasting resulted in a significant increase of serum adiponectin (P< 0.000, fasting glucose (P< 0.000 and triglycride (P< 0.001. Body mass index was lowered during the fasting (P< 0.000. Finally, no remarkable decrease was found in serum TNF-α levels (P= 0.100. Conclusion: Ramadan fasting resulted in augmented adiponectin levels which may help in improving metabolic stress induced by insulin resistance in men with predisposing factors of type2 DM.

  15. Bitter taste receptors influence glucose homeostasis.

    Science.gov (United States)

    Dotson, Cedrick D; Zhang, Lan; Xu, Hong; Shin, Yu-Kyong; Vigues, Stephan; Ott, Sandra H; Elson, Amanda E T; Choi, Hyun Jin; Shaw, Hillary; Egan, Josephine M; Mitchell, Braxton D; Li, Xiaodong; Steinle, Nanette I; Munger, Steven D

    2008-01-01

    TAS1R- and TAS2R-type taste receptors are expressed in the gustatory system, where they detect sweet- and bitter-tasting stimuli, respectively. These receptors are also expressed in subsets of cells within the mammalian gastrointestinal tract, where they mediate nutrient assimilation and endocrine responses. For example, sweeteners stimulate taste receptors on the surface of gut enteroendocrine L cells to elicit an increase in intracellular Ca(2+) and secretion of the incretin hormone glucagon-like peptide-1 (GLP-1), an important modulator of insulin biosynthesis and secretion. Because of the importance of taste receptors in the regulation of food intake and the alimentary responses to chemostimuli, we hypothesized that differences in taste receptor efficacy may impact glucose homeostasis. To address this issue, we initiated a candidate gene study within the Amish Family Diabetes Study and assessed the association of taste receptor variants with indicators of glucose dysregulation, including a diagnosis of type 2 diabetes mellitus and high levels of blood glucose and insulin during an oral glucose tolerance test. We report that a TAS2R haplotype is associated with altered glucose and insulin homeostasis. We also found that one SNP within this haplotype disrupts normal responses of a single receptor, TAS2R9, to its cognate ligands ofloxacin, procainamide and pirenzapine. Together, these findings suggest that a functionally compromised TAS2R receptor negatively impacts glucose homeostasis, providing an important link between alimentary chemosensation and metabolic disease.

  16. Bitter taste receptors influence glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Cedrick D Dotson

    Full Text Available TAS1R- and TAS2R-type taste receptors are expressed in the gustatory system, where they detect sweet- and bitter-tasting stimuli, respectively. These receptors are also expressed in subsets of cells within the mammalian gastrointestinal tract, where they mediate nutrient assimilation and endocrine responses. For example, sweeteners stimulate taste receptors on the surface of gut enteroendocrine L cells to elicit an increase in intracellular Ca(2+ and secretion of the incretin hormone glucagon-like peptide-1 (GLP-1, an important modulator of insulin biosynthesis and secretion. Because of the importance of taste receptors in the regulation of food intake and the alimentary responses to chemostimuli, we hypothesized that differences in taste receptor efficacy may impact glucose homeostasis. To address this issue, we initiated a candidate gene study within the Amish Family Diabetes Study and assessed the association of taste receptor variants with indicators of glucose dysregulation, including a diagnosis of type 2 diabetes mellitus and high levels of blood glucose and insulin during an oral glucose tolerance test. We report that a TAS2R haplotype is associated with altered glucose and insulin homeostasis. We also found that one SNP within this haplotype disrupts normal responses of a single receptor, TAS2R9, to its cognate ligands ofloxacin, procainamide and pirenzapine. Together, these findings suggest that a functionally compromised TAS2R receptor negatively impacts glucose homeostasis, providing an important link between alimentary chemosensation and metabolic disease.

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... events, such as eating breakfast, take on exaggerated importance. It's a world where a person needs a ... Living With Diabetes Treatment and Care Blood Glucose Testing Checking Your Blood Glucose A1C and eAG Hypoglycemia ( ...

  18. Augmented reality in medical education?

    Science.gov (United States)

    Kamphuis, Carolien; Barsom, Esther; Schijven, Marlies; Christoph, Noor

    2014-09-01

    Learning in the medical domain is to a large extent workplace learning and involves mastery of complex skills that require performance up to professional standards in the work environment. Since training in this real-life context is not always possible for reasons of safety, costs, or didactics, alternative ways are needed to achieve clinical excellence. Educational technology and more specifically augmented reality (AR) has the potential to offer a highly realistic situated learning experience supportive of complex medical learning and transfer. AR is a technology that adds virtual content to the physical real world, thereby augmenting the perception of reality. Three examples of dedicated AR learning environments for the medical domain are described. Five types of research questions are identified that may guide empirical research into the effects of these learning environments. Up to now, empirical research mainly appears to focus on the development, usability and initial implementation of AR for learning. Limited review results reflect the motivational value of AR, its potential for training psychomotor skills and the capacity to visualize the invisible, possibly leading to enhanced conceptual understanding of complex causality.

  19. Psychotherapy augmentation through preconscious priming

    Directory of Open Access Journals (Sweden)

    Francois eBorgeat

    2013-03-01

    Full Text Available Objective: To test the hypothesis that repeated preconscious (masked priming of personalized positive cognitions could augment cognitive change and facilitate achievement of patients’ goals following a therapy.Methods: Twenty social phobic patients (13 women completed a 36 weeks study beginning by 12 weeks of group behavioural therapy. After the therapy, they received 6 weeks of preconscious priming and 6 weeks of a control procedure in a randomized cross-over design. The Priming condition involved listening twice daily with a passive attitude to a recording of individualized formulations of appropriate cognitions and attitudes masked by music. The Control condition involved listening to an indistinguishable recording where the formulations had been replaced by random numbers. Changes in social cognitions were measured by the Social Interaction Self Statements Test (SISST.Results: Patients improved following therapy. The Priming procedure was associated with increased positive cognitions and decreased negative cognitions on the SISST while the Control procedure was not. The Priming procedure induced more cognitive change when applied immediately after the group therapy. Conclusion: An effect of priming was observed on social phobia related cognitions in the expected direction. This self administered addition to a therapy could be seen as an augmentation strategy.

  20. Interactive Assembly Guide using Augmented Reality

    DEFF Research Database (Denmark)

    Andersen, Martin; Andersen, Rasmus Skovgaard; Larsen, Christian Lindequist

    2009-01-01

    This paper presents an Augmented Reality system for aiding a pump assembling process at Grundfos, one of the leading pump producers. Stable pose estimation of the pump is required in order to augment the graphics correctly. This is achieved by matching image edges with synthesized edges from CAD...... norm. A dynamic visualization of the augmented graphics provides the user with guidance. Usability tests show that the accuracy of the system is sufficient for assembling the pump....

  1. Augmented Reality for Maintenance and Repair (ARMAR)

    Science.gov (United States)

    2007-08-01

    The purpose of this research, Augmented Reality for Maintenance and Repair (ARMAR), was to research the design and development of experimental... augmented reality systems for maintenance job aiding. The goal was to explore and evaluate the feasibility of developing prototype adaptive augmented ... reality systems that can be used to investigate how real time computer graphics, overlaid on and registered with the actual equipment being maintained, can

  2. InAR:Inverse Augmented Reality

    OpenAIRE

    Hu, Hao; Cui, Hainan

    2015-01-01

    Augmented reality is the art to seamlessly fuse virtual objects into real ones. In this short note, we address the opposite problem, the inverse augmented reality, that is, given a perfectly augmented reality scene where human is unable to distinguish real objects from virtual ones, how the machine could help do the job. We show by structure from motion (SFM), a simple 3D reconstruction technique from images in computer vision, the real and virtual objects can be easily separated in the recon...

  3. Striae distensae after subfascial breast augmentation.

    Science.gov (United States)

    Keramidas, Evangelos; Rodopoulou, Stavroula

    2008-03-01

    Striae distensae or stretch marks after breast augmentation are a rare complication. To date, 10 cases have been published. In seven of these cases, the implant was placed in a subglandular position and in the other three cases, placement was submuscular. Two cases of stretch marks in two young nulliparous women who underwent subfacial breast augmentation are presented. To the best of the authors' knowledge, this is the first report of striae distensae after subfascial breast augmentation.

  4. INTEGRATIVE AUGMENTATION OF STANDARDIZED MANAGEMENT SYSTEMS

    Directory of Open Access Journals (Sweden)

    Stanislav Karapetrovic

    2008-03-01

    Full Text Available The development, features and integrating abilities of different international standards related to management systems are discussed. A group of such standards that augment the performance of quality management systems in organizations is specifically focused on. The concept, characteristics and an illustrative example of one augmenting standard, namely ISO 10001, are addressed. Integration of standardized augmenting systems, both by themselves and within the overall management system, is examined. It is argued that, in research and practice alike, integrative augmentation represents the future of standardized quality and other management systems.

  5. RFIDice - Augmenting Tabletop Dice with RFID

    Directory of Open Access Journals (Sweden)

    Marc Langheinrich

    2008-08-01

    Full Text Available Augmented dice allow players of tabletop games to have the result of a roll be automatically recorded by a computer, e.g., for supporting strategy games. We have built a set of three augmented-dice-prototypes based on radio frequency identification (RFID technology, which allows us to build robust, cheap, and small augmented dice. Using a corresponding readout infrastructure and a sample application, we have evaluated our approach and show its advantages over other dice augmentation methods discussed in the literature.

  6. Resolving futile glucose cycling and glycogenolytic contributions to plasma glucose levels following a glucose load

    NARCIS (Netherlands)

    Nunes, P.M.; Jarak, I.; Heerschap, A.; Jones, J.G.

    2014-01-01

    PURPOSE: After a glucose load, futile glucose/glucose-6-phosphate (G6P) cycling (FGC) generates [2-(2) H]glucose from (2) H2 O thereby mimicking a paradoxical glycogenolytic contribution to plasma glucose levels. Contributions of load and G6P derived from gluconeogenesis, FGC, and glycogenolysis to

  7. Why Do SGLT2 Inhibitors Inhibit Only 30–50% of Renal Glucose Reabsorption in Humans?

    OpenAIRE

    Liu, Jiwen; Lee, TaeWeon; DeFronzo, Ralph A.

    2012-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for diabetes under late-stage clinical development. It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption. However, SGLT2 inhibitors in clinical development inhibit only 30–50% of the filtered glucose load. Why are they unable to inhibit 90% of glucose reabsorption in humans? We will try to provide an explanation to this puzzle in this perspective analysis of the unique pharmacokineti...

  8. Kidney transplantation improves arterial function measured by pulse wave analysis and endothelium-independent dilatation in uraemic patients despite deterioration of glucose metabolism

    DEFF Research Database (Denmark)

    Hornum, Mads; Clausen, Peter; Idorn, Thomas

    2011-01-01

    BACKGROUND: The aim of this study is to investigate the effect of kidney transplantation on arterial function in relation to changes in glucose metabolism. METHODS: Included were 40 kidney recipients (Tx group, age 38 ± 13 years) and 40 patients without known diabetes remaining on the waiting list...... for kidney transplantation (uraemic control group, age 47 ± 11 years). Arterial function was estimated by the pulse wave velocity (PWV) of the carotid-femoral pulse wave, aortic augmentation index (AIX), flow-mediated (FMD) and nitroglycerin-induced vasodilatation (NID) of the brachial artery performed...... before transplantation and after 12 months. PWV recorded sequentially at the carotid and femoral artery is an estimate of arterial stiffness; AIX is an integrated index of vascular and ventricular function. FMD and NID are the dilatory capacities of the brachial artery after increased flow (endothelium...

  9. Glucose screening tests during pregnancy

    Science.gov (United States)

    Oral glucose tolerance test - pregnancy; OGTT - pregnancy; Glucose challenge test - pregnancy; Gestational diabetes - glucose screening ... screening test between 24 and 28 weeks of pregnancy. The test may be done earlier if you ...

  10. Augmented reinforcer value and accelerated habit formation after repeated amphetamine treatment.

    NARCIS (Netherlands)

    Nordquist, R.E.; Voorn, P.; de Mooij-van Malsen, J.G.; Joosten, R.N.J.M.A.; Pennartz, C.M.A.; Vanderschuren, L.J.M.J.

    2007-01-01

    Various processes might explain the progression from casual to compulsive drug use underlying the development of drug addiction. Two of these, accelerated stimulus-response (S-R) habit learning and augmented assignment of motivational value to reinforcers, could be mediated via neuroadaptations asso

  11. Augmented reality for improved safety

    CERN Multimedia

    Stefania Pandolfi

    2016-01-01

    Sometimes, CERN experts have to operate in low visibility conditions or in the presence of possible hazards. Minimising the duration of the operation and reducing the risk of errors is therefore crucial to ensuring the safety of personnel. The EDUSAFE project integrates different technologies to create a wearable personnel safety system based on augmented reality.    The EDUSAFE integrated safety system uses a camera mounted on the helmet to monitor the working area.  In its everyday operation of machines and facilities, CERN adopts a whole set of measures and safety equipment to ensure the safety of its personnel, including personal wearable safety devices and access control systems. However, sometimes, scheduled and emergency maintenance work needs to be done in zones with potential cryogenic hazards, in the presence of radioactive equipment or simply in demanding conditions where visibility is low and moving around is difficult. The EDUSAFE Marie Curie Innovative&...

  12. LOFT Augmented Operator Capability Program

    Energy Technology Data Exchange (ETDEWEB)

    Hollenbeck, D.A.; Krantz, E.A.; Hunt, G.L.; Meyer, O.R.

    1980-01-01

    The outline of the LOFT Augmented Operator Capability Program is presented. This program utilizes the LOFT (Loss-of-Fluid Test) reactor facility which is located at the Idaho National Engineering Laboratory and the LOFT operational transient experiment series as a test bed for methods of enhancing the reactor operator's capability for safer operation. The design of an Operational Diagnotics and Display System is presented which was backfit to the existing data acquisition computers. Basic color-graphic displays of the process schematic and trend type are presented. In addition, displays were developed and are presented which represent safety state vector information. A task analysis method was applied to LOFT reactor operating procedures to test its usefulness in defining the operator's information needs and workload.

  13. Keratin 8/18 regulation of glucose metabolism in normal versus cancerous hepatic cells through differential modulation of hexokinase status and insulin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, Jasmin; Loranger, Anne; Gilbert, Stéphane [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada); Faure, Robert [Département de Pédiatrie, Université Laval and Centre de recherche du CHUQ (Centre Mère-Enfant), Québec, Qc, Canada G1V 4G2 (Canada); Marceau, Normand, E-mail: normand.marceau@crhdq.ulaval.ca [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada)

    2013-02-15

    As differentiated cells, hepatocytes primarily metabolize glucose for ATP production through oxidative phosphorylation of glycolytic pyruvate, whereas proliferative hepatocellular carcinoma (HCC) cells undergo a metabolic shift to aerobic glycolysis despite oxygen availability. Keratins, the intermediate filament (IF) proteins of epithelial cells, are expressed as pairs in a lineage/differentiation manner. Hepatocyte and HCC (hepatoma) cell IFs are made solely of keratins 8/18 (K8/K18), thus providing models of choice to address K8/K18 IF functions in normal and cancerous epithelial cells. Here, we demonstrate distinctive increases in glucose uptake, glucose-6-phosphate formation, lactate release, and glycogen formation in K8/K18 IF-lacking hepatocytes and/or hepatoma cells versus their respective IF-containing counterparts. We also show that the K8/K18-dependent glucose uptake/G6P formation is linked to alterations in hexokinase I/II/IV content and localization at mitochondria, with little effect on GLUT1 status. In addition, we find that the insulin-stimulated glycogen formation in normal hepatocytes involves the main PI-3 kinase-dependent signaling pathway and that the K8/K18 IF loss makes them more efficient glycogen producers. In comparison, the higher insulin-dependent glycogen formation in K8/K18 IF-lacking hepatoma cells is associated with a signaling occurring through a mTOR-dependent pathway, along with an augmentation in cell proliferative activity. Together, the results uncover a key K8/K18 regulation of glucose metabolism in normal and cancerous hepatic cells through differential modulations of mitochondrial HK status and insulin-mediated signaling.

  14. Enhancing Education through Mobile Augmented Reality

    Science.gov (United States)

    Joan, D. R. Robert

    2015-01-01

    In this article, the author has discussed about the Mobile Augmented Reality and enhancing education through it. The aim of the present study was to give some general information about mobile augmented reality which helps to boost education. Purpose of the current study reveals the mobile networks which are used in the institution campus as well…

  15. From Augmentation Media to Meme Media.

    Science.gov (United States)

    Tanaka, Yuzuru

    Computers as meta media are now evolving from augmentation media vehicles to meme media vehicles. While an augmentation media system provides a seamlessly integrated environment of various tools and documents, meme media system provides further functions to edit and distribute tools and documents. Documents and tools on meme media can easily…

  16. Augmented Reality Interfaces for Additive Manufacturing

    DEFF Research Database (Denmark)

    Eiríksson, Eyþór Rúnar; Pedersen, David Bue; Frisvad, Jeppe Revall

    2017-01-01

    This paper explores potential use cases for using augmented reality (AR) as a tool to operate industrial machines. As a baseline we use an additive manufacturing system, more commonly known as a 3D printer. We implement novel augmented interfaces and controls using readily available open source...

  17. Motor skill learning: age and augmented feedback

    NARCIS (Netherlands)

    Dijk, van Henk

    2006-01-01

    Learning motor skills is fundamental to human life. One of the most critical variables affecting motor learning, aside from practice itself, is augmented feedback (performance-related information). Although there is abundance of research on how young adults use augmented feedback to learn motor skil

  18. Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter-1 protein.

    Science.gov (United States)

    Tang, Maoxue; Gao, Guangping; Rueda, Carlos B; Yu, Hang; Thibodeaux, David N; Awano, Tomoyuki; Engelstad, Kristin M; Sanchez-Quintero, Maria-Jose; Yang, Hong; Li, Fanghua; Li, Huapeng; Su, Qin; Shetler, Kara E; Jones, Lynne; Seo, Ryan; McConathy, Jonathan; Hillman, Elizabeth M; Noebels, Jeffrey L; De Vivo, Darryl C; Monani, Umrao R

    2017-01-20

    Haploinsufficiency of the SLC2A1 gene and paucity of its translated product, the glucose transporter-1 (Glut1) protein, disrupt brain function and cause the neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). There is little to suggest how reduced Glut1 causes cognitive dysfunction and no optimal treatment for Glut1 DS. We used model mice to demonstrate that low Glut1 protein arrests cerebral angiogenesis, resulting in a profound diminution of the brain microvasculature without compromising the blood-brain barrier. Studies to define the temporal requirements for Glut1 reveal that pre-symptomatic, AAV9-mediated repletion of the protein averts brain microvasculature defects and prevents disease, whereas augmenting the protein late, during adulthood, is devoid of benefit. Still, treatment following symptom onset can be effective; Glut1 repletion in early-symptomatic mutants that have experienced sustained periods of low brain glucose nevertheless restores the cerebral microvasculature and ameliorates disease. Timely Glut1 repletion may thus constitute an effective treatment for Glut1 DS.

  19. Maternal Fat Feeding Augments Offspring Nephron Endowment in Mice

    Science.gov (United States)

    Hokke, Stacey; Puelles, Victor G.; Armitage, James A.; Fong, Karen; Bertram, John F.; Cullen-McEwen, Luise A.

    2016-01-01

    Increasing consumption of a high fat 'Western' diet has led to a growing number of pregnancies complicated by maternal obesity. Maternal overnutrition and obesity have health implications for offspring, yet little is known about their effects on offspring kidney development and renal function. Female C57Bl6 mice were fed a high fat diet (HFD, 21% fat) or matched normal fat diet (NFD, 6% fat) for 6 weeks prior to pregnancy and throughout gestation and lactation. HFD dams were overweight and glucose intolerant prior to mating but not in late gestation. Offspring of NFD and HFD dams had similar body weights at embryonic day (E)15.5, E18.5 and at postnatal day (PN)21. HFD offspring had normal ureteric tree development and nephron number at E15.5. However, using unbiased stereology, kidneys of HFD offspring were found to have 20–25% more nephrons than offspring of NFD dams at E18.5 and PN21. Offspring of HFD dams with body weight and glucose profiles similar to NFD dams prior to pregnancy also had an elevated nephron endowment. At 9 months of age, adult offspring of HFD dams displayed mild fasting hyperglycaemia but similar body weights to NFD offspring. Renal function and morphology, measured by transcutaneous clearance of FITC-sinistrin and stereology respectively, were normal. This study demonstrates that maternal fat feeding augments offspring nephron endowment with no long-term consequences for offspring renal health. Future studies assessing the effects of a chronic stressor on adult mice with augmented nephron number are warranted, as are studies investigating the molecular mechanisms that result in high nephron endowment. PMID:27547968

  20. Aspects of User Experience in Augmented Reality

    DEFF Research Database (Denmark)

    Madsen, Jacob Boesen

    In Augmented Reality applications, the real environment is annotated or enhanced with computer-generated graphics. This is a topic that has been researched in the recent decades, but for many people this is a brand new and never heard of topic. The main focus of this thesis is investigations...... in human factors related to Augmented Reality. This is investigated partly as how Augmented Reality applications are used in unsupervised settings, and partly in specific evaluations related to user performance in supervised settings. The thesis starts by introducing Augmented Reality to the reader......, followed by a presentation of the technical areas related to the field, and different human factor areas. As a contribution to the research area, this thesis presents five separate, but sequential, papers within the area of Augmented Reality....

  1. Diffuser Augmented Horizontal Axis Tidal Current Turbines

    Directory of Open Access Journals (Sweden)

    Nasir Mehmood

    2012-09-01

    Full Text Available The renewal energy technologies are increasingly popular to ensure future energy sustenance and address environmental issues. The tides are enormous and consistent untapped resource of renewable energy. The growing interest in exploring tidal energy has compelling reasons such as security and diversity of supply, intermittent but predictable and limited social and environmental impacts. The tidal energy industry is undergoing an increasing shift towards diffuser augmented turbines. The reason is the higher power output of diffuser augmented turbines compared to conventional open turbines. The purpose of this study is to present a comprehensive review of diffuser augmented horizontal axis tidal current turbines. The components, relative advantages, limitations and design parameters of diffuser augmented horizontal axis tidal current turbines are presented in detail. CFD simulation of NACA 0016 airfoil is carried out to explore its potential for designing a diffuser. The core issues associated with diffuser augmented horizontal axis tidal current turbines are also discussed.

  2. Augmented Reality Implementation Methods in Mainstream Applications

    CERN Document Server

    Prochazka, David

    2011-01-01

    Augmented reality has became an useful tool in many areas from space exploration to military applications. Although used theoretical principles are well known for almost a decade, the augmented reality is almost exclusively used in high budget solutions with a special hardware. However, in last few years we could see rising popularity of many projects focused on deployment of the augmented reality on different mobile devices. Our article is aimed on developers who consider development of an augmented reality application for the mainstream market. Such developers will be forced to keep the application price, therefore also the development price, at reasonable level. Usage of existing image processing software library could bring a significant cut-down of the development costs. In the theoretical part of the article is presented an overview of the augmented reality application structure. Further, an approach for selection appropriate library as well as the review of the existing software libraries focused in th...

  3. Unconjugated bilirubin mediates heme oxygenase-1-induced vascular benefits in diabetic mice.

    Science.gov (United States)

    Liu, Jian; Wang, Li; Tian, Xiao Yu; Liu, Limei; Wong, Wing Tak; Zhang, Yang; Han, Quan-Bin; Ho, Hing-Man; Wang, Nanping; Wong, Siu Ling; Chen, Zhen-Yu; Yu, Jun; Ng, Chi-Fai; Yao, Xiaoqiang; Huang, Yu

    2015-05-01

    Heme oxygenase-1 (HO-1) exerts vasoprotective effects. Such benefit in diabetic vasculopathy, however, remains unclear. We hypothesize that bilirubin mediates HO-1-induced vascular benefits in diabetes. Diabetic db/db mice were treated with hemin (HO-1 inducer) for 2 weeks, and aortas were isolated for functional and molecular assays. Nitric oxide (NO) production was measured in cultured endothelial cells. Hemin treatment augmented endothelium-dependent relaxations (EDRs) and elevated Akt and endothelial NO synthase (eNOS) phosphorylation in db/db mouse aortas, which were reversed by the HO-1 inhibitor SnMP or HO-1 silencing virus. Hemin treatment increased serum bilirubin, and ex vivo bilirubin treatment improved relaxations in diabetic mouse aortas, which was reversed by the Akt inhibitor. Biliverdin reductase silencing virus attenuated the effect of hemin. Chronic bilirubin treatment improved EDRs in db/db mouse aortas. Hemin and bilirubin reversed high glucose-induced reductions in Akt and eNOS phosphorylation and NO production. The effect of hemin but not bilirubin was inhibited by biliverdin reductase silencing virus. Furthermore, bilirubin augmented EDRs in renal arteries from diabetic patients. In summary, HO-1-induced restoration of endothelial function in diabetic mice is most likely mediated by bilirubin, which preserves NO bioavailability through the Akt/eNOS/NO cascade, suggesting bilirubin as a potential therapeutic target for clinical intervention of diabetic vasculopathy.

  4. Sex steroids and glucose metabolism

    Directory of Open Access Journals (Sweden)

    Carolyn A Allan

    2014-04-01

    Full Text Available Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus (T2DM and also predict the onset of these adverse metabolic states. Body composition (body mass index, waist circumference is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter's syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain.

  5. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... an Employer Options for the Uninsured Medicare Medicaid & CHIP For Parents & Kids Safe at School Everyday Life ... blood sugar). High blood glucose happens when the body has too little insulin or when the body ...

  13. Nocturnal continuous glucose monitoring

    DEFF Research Database (Denmark)

    Bay, Christiane; Kristensen, Peter Lommer; Pedersen-Bjergaard, Ulrik;

    2013-01-01

    Abstract Background: A reliable method to detect biochemical nocturnal hypoglycemia is highly needed, especially in patients with recurrent severe hypoglycemia. We evaluated reliability of nocturnal continuous glucose monitoring (CGM) in patients with type 1 diabetes at high risk of severe...

  14. Hyperglycemia (High Blood Glucose)

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  7. Stimulation of glucose uptake in murine soleus muscle and adipocytes by 5-(4-phenoxybutoxypsoralen (PAP-1 may be mediated by Kv1.5 rather than Kv1.3

    Directory of Open Access Journals (Sweden)

    Robert A. Ngala

    2014-10-01

    Full Text Available Kv1 channels are shaker-related potassium channels that influence insulin sensitivity. Kv1.3−/− mice are protected from diet-induced insulin resistance and some studies suggest that Kv1.3 inhibitors provide similar protection. However, it is unclear whether blockade of Kv1.3 in adipocytes or skeletal muscle increases glucose uptake. There is no evidence that the related channel Kv1.5 has any influence on insulin sensitivity and its expression in adipose tissue has not been reported. PAP-1 is a selective inhibitor of Kv1.3, with 23-fold, 32-fold and 125-fold lower potencies as an inhibitor of Kv1.5, Kv1.1 and Kv1.2 respectively. Soleus muscles from wild-type and genetically obese ob/ob mice were incubated with 2-deoxy[1-14C]-glucose for 45 min and formation of 2-deoxy[1-14C]-glucose-6-phosphate was measured. White adipocytes were incubated with D-[U-14C]-glucose for 1 h. TNFα and Il-6 secretion from white adipose tissue pieces were measured by enzyme-linked-immunoassay. In the absence of insulin, a high concentration (3 µM of PAP-1 stimulated 2-deoxy[1-14C]-glucose uptake in soleus muscle of wild-type and obese mice by 30% and 40% respectively, and in adipocytes by 20% and 50% respectively. PAP-1 also stimulated glucose uptake by adipocytes at the lower concentration of 1 µM, but at 300 nM, which is still 150-fold higher than its EC50 value for inhibition of the Kv1.3 channel, it had no effect. In the presence of insulin, PAP-1 (3 µM had a significant effect only in adipocytes from obese mice. PAP-1 (3 µM reduced the secretion of TNFα by adipose tissue but had no effect on the secretion of IL-6. Expression of Kv1.1, Kv1.2, Kv1.3 and Kv1.5 was determined by RT-PCR. Kv1.3 and Kv1.5 mRNA were detected in liver, gastrocnemius muscle, soleus muscle and white adipose tissue from wild-type and ob/ob mice, except that Kv1.3 could not be detected in gastrocnemius muscle, nor Kv1.5 in liver, of wild-type mice. Expression of both genes was

  8. Cell motility in models of wounded human skin is improved by Gap27 despite raised glucose, insulin and IGFBP-5

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Catherine S.; Berends, Rebecca F. [Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA (United Kingdom); Flint, David J. [Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE (United Kingdom); Martin, Patricia E.M., E-mail: Patricia.Martin@gcu.ac.uk [Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA (United Kingdom)

    2013-02-15

    Reducing Cx43 expression stimulates skin wound healing. This is mimicked in models when Cx43 function is blocked by the connexin mimetic peptide Gap27. IGF-I also stimulates wound healing with IGFBP-5 attenuating its actions. Further, the IGF-I to IGFBP-5 ratio is altered in diabetic skin, where wound closure is impaired. We investigated whether Gap27 remains effective in augmenting scrape-wound closure in human skin wound models simulating diabetes-induced changes, using culture conditions with raised glucose, insulin and IGFBP-5. Gap27 increased scrape-wound closure in normal glucose and insulin (NGI) and to a lesser extent in high glucose and insulin (HGI). IGF-I enhanced scrape-wound closure in keratinocytes whereas IGFBP-5 inhibited this response. Gap27 overcame the inhibitory effects of IGFBP-5 on IGF-I activity. Connexin-mediated communication (CMC) was reduced in HGI, despite raised Cx43, and Gap27 significantly decreased CMC in NGI and HGI. IGF-I and IGFBP-5 did not affect CMC. IGF-I increased keratinocyte proliferation in NGI, and Gap27 increased proliferation in NGI to a greater extent than in HGI. We conclude that IGF-I and Gap27 stimulate scrape-wound closure by independent mechanisms with Gap27 inhibiting Cx43 function. Gap27 can enhance wound closure in diabetic conditions, irrespective of the IGF-I:IGFBP-5 balance. - Highlights: ► Human organotypic and keratinocyte ‘diabetic’ skin models were used to demonstrate the ability of Gap27 to improve scrape-wound closure. ► Gap27 enhanced scrape-wound closure by reducing Cx43-mediated communication, whereas IGFBP-5 retarded cell migration. ► IGF-I and IGFBP-5 did not affect connexin-mediated pathways. ► Gap27 can override altered glucose, insulin, IGF-I, and IGFBP-5 in ‘diabetic’ skin models and thus has therapeutic potential.

  9. Mitochondrial antioxidative capacity regulates muscle glucose uptake in the conscious mouse: effect of exercise and diet.

    Science.gov (United States)

    Kang, Li; Lustig, Mary E; Bonner, Jeffrey S; Lee-Young, Robert S; Mayes, Wesley H; James, Freyja D; Lin, Chien-Te; Perry, Christopher G R; Anderson, Ethan J; Neufer, P Darrell; Wasserman, David H

    2012-10-15

    The objective of this study was to test the hypothesis that exercise-stimulated muscle glucose uptake (MGU) is augmented by increasing mitochondrial reactive oxygen species (mtROS) scavenging capacity. This hypothesis was tested in genetically altered mice fed chow or a high-fat (HF) diet that accelerates mtROS formation. Mice overexpressing SOD2 (sod2(Tg)), mitochondria-targeted catalase (mcat(Tg)), and combined SOD2 and mCAT (mtAO) were used to increase mtROS scavenging. mtROS was assessed by the H(2)O(2) emitting potential (JH(2)O(2)) in muscle fibers. sod2(Tg) did not decrease JH(2)O(2) in chow-fed mice, but decreased JH(2)O(2) in HF-fed mice. mcat(Tg) and mtAO decreased JH(2)O(2) in both chow- and HF-fed mice. In parallel, the ratio of reduced to oxidized glutathione (GSH/GSSG) was unaltered in sod2(Tg) in chow-fed mice, but was increased in HF-fed sod2(Tg) and both chow- and HF-fed mcat(Tg) and mtAO. Nitrotyrosine, a marker of NO-dependent, reactive nitrogen species (RNS)-induced nitrative stress, was decreased in both chow- and HF-fed sod2(Tg), mcat(Tg), and mtAO mice. This effect was not changed with exercise. Kg, an index of MGU was assessed using 2-[(14)C]-deoxyglucose during exercise. In chow-fed mice, sod2(Tg), mcat(Tg), and mtAO increased exercise Kg compared with wild types. Exercise Kg was also augmented in HF-fed sod2(Tg) and mcat(Tg) mice but unchanged in HF-fed mtAO mice. In conclusion, mtROS scavenging is a key regulator of exercise-mediated MGU and this regulation depends on nutritional state.

  10. Responsiveness to D-glucose in neurosecretory cells of crustaceans.

    Science.gov (United States)

    García, E; Benítez, A; Onetti, C G

    1993-08-01

    1. An electrophysiological study of the D-glucose sensitivity of X-organ (XO) neurosecretory cell bodies in crayfish was carried out with the use of microelectrodes, perforated, and cell-attached patch-clamp techniques. 2. Glucose depolarizes the membrane potential of XO cells in a concentration-dependent manner. 3. Depolarization produced by glucose initiates a change in the pattern of electrical activity. Silent cells began to discharge action potentials. When bursting cells are depolarized by glucose, their action potentials are no longer grouped in bursts or disappear entirely. 4. Although the membrane potential returns to its initial value after removing glucose from the bath, discharge patterns of the cells may remain different. This suggests that besides the depolarizing effect, once the cells have been exposed to glucose, the sugar switches on a process that is maintained for a long time. 5. Glucose produced a reduction of membrane steady-state conductance, and a shift of reversal potential of membrane currents to a more positive value. 6. Depolarization induced by D-glucose appears to be related with a closure of potassium channels. 7. Glucose effect was thought to be generated by a product of metabolism that would act as intracellular mediator.

  11. Augmented reality in surgical procedures

    Science.gov (United States)

    Samset, E.; Schmalstieg, D.; Vander Sloten, J.; Freudenthal, A.; Declerck, J.; Casciaro, S.; Rideng, Ø.; Gersak, B.

    2008-02-01

    Minimally invasive therapy (MIT) is one of the most important trends in modern medicine. It includes a wide range of therapies in videoscopic surgery and interventional radiology and is performed through small incisions. It reduces hospital stay-time by allowing faster recovery and offers substantially improved cost-effectiveness for the hospital and the society. However, the introduction of MIT has also led to new problems. The manipulation of structures within the body through small incisions reduces dexterity and tactile feedback. It requires a different approach than conventional surgical procedures, since eye-hand co-ordination is not based on direct vision, but more predominantly on image guidance via endoscopes or radiological imaging modalities. ARIS*ER is a multidisciplinary consortium developing a new generation of decision support tools for MIT by augmenting visual and sensorial feedback. We will present tools based on novel concepts in visualization, robotics and haptics providing tailored solutions for a range of clinical applications. Examples from radio-frequency ablation of liver-tumors, laparoscopic liver surgery and minimally invasive cardiac surgery will be presented. Demonstrators were developed with the aim to provide a seamless workflow for the clinical user conducting image-guided therapy.

  12. Postauricular fascia in augmentation rhinoplasty.

    Science.gov (United States)

    Guerra, Aldo Benjamin

    2014-06-01

    Ten rhinoplasty operations performed using postauricular fascia for the purpose of augmenting the radix and dorsum of the nose were analyzed retrospectively. All the operations were performed over a 1-year period, between 2005 and 2006. The fascia of the postauricular area has been used as a source of pliable soft-tissue grafts in primary and revision rhinoplasty. It may be easily accessed using a single sulcus incision that also enables harvesting of ear cartilage grafts. Deficiency in the radix is an overlooked abnormality seen in many patients undergoing primary as well as revision rhinoplasty after aggressive hump removal. Recent trends in rhinoplasty have been to avoid the overly reduced nasal skeleton and to create a more balanced nasal surgery result. This article presents the use of the postauricular fascia as a radix graft that has been found to be simple to carry out, reliable, and long lasting. In addition, the fascia graft is useful in the camouflage of various nasal deformities in the dorsum and sidewalls. The average patient follow-up for the study was 24 months.

  13. Digital Augmented Reality Audio Headset

    Directory of Open Access Journals (Sweden)

    Jussi Rämö

    2012-01-01

    Full Text Available Augmented reality audio (ARA combines virtual sound sources with the real sonic environment of the user. An ARA system can be realized with a headset containing binaural microphones. Ideally, the ARA headset should be acoustically transparent, that is, it should not cause audible modification to the surrounding sound. A practical implementation of an ARA mixer requires a low-latency headphone reproduction system with additional equalization to compensate for the attenuation and the modified ear canal resonances caused by the headphones. This paper proposes digital IIR filters to realize the required equalization and evaluates a real-time prototype ARA system. Measurements show that the throughput latency of the digital prototype ARA system can be less than 1.4 ms, which is sufficiently small in practice. When the direct and processed sounds are combined in the ear, a comb filtering effect is brought about and appears as notches in the frequency response. The comb filter effect in speech and music signals was studied in a listening test and it was found to be inaudible when the attenuation is 20 dB. Insert ARA headphones have a sufficient attenuation at frequencies above about 1 kHz. The proposed digital ARA system enables several immersive audio applications, such as a virtual audio tourist guide and audio teleconferencing.

  14. Wireless Augmented Reality Prototype (WARP)

    Science.gov (United States)

    Devereaux, A. S.

    1999-01-01

    Initiated in January, 1997, under NASA's Office of Life and Microgravity Sciences and Applications, the Wireless Augmented Reality Prototype (WARP) is a means to leverage recent advances in communications, displays, imaging sensors, biosensors, voice recognition and microelectronics to develop a hands-free, tetherless system capable of real-time personal display and control of computer system resources. Using WARP, an astronaut may efficiently operate and monitor any computer-controllable activity inside or outside the vehicle or station. The WARP concept is a lightweight, unobtrusive heads-up display with a wireless wearable control unit. Connectivity to the external system is achieved through a high-rate radio link from the WARP personal unit to a base station unit installed into any system PC. The radio link has been specially engineered to operate within the high- interference, high-multipath environment of a space shuttle or space station module. Through this virtual terminal, the astronaut will be able to view and manipulate imagery, text or video, using voice commands to control the terminal operations. WARP's hands-free access to computer-based instruction texts, diagrams and checklists replaces juggling manuals and clipboards, and tetherless computer system access allows free motion throughout a cabin while monitoring and operating equipment.

  15. Augmented reality: past, present, future

    Science.gov (United States)

    Inzerillo, Laura

    2013-03-01

    A great opportunity has permitted to carry out a cultural, historical, architectural and social research with great impact factor on the international cultural interest. We are talking about the realization of a museum whose the main theme is the visit and the discovery of a monument of great prestige: the monumental building the "Steri" in Palermo. The museum is divided into sub themes including the one above all, that has aroused the international interest so much that it has been presented the instance to include the museum in the cultural heritage of UNESCO. It is the realization of a museum path that regards the cells of the Inquisition, which are located just inside of some buildings of the monumental building. The project, as a whole, is faced, in a total view, between the various competences implicated: historic, chemic, architectonic, topographic, drawing, representation, virtual communication, informatics. The birth of the museum will be a sum of the results of all these disciplines involved. Methodology, implementation, fruition, virtual museum, goals, 2D graphic restitution, effects on the cultural heritage and landscape environmental, augmented reality, Surveying 2D and 3D, hi-touch screen, Photogrammetric survey, Photographic survey, representation, drawing 3D and more than this has been dealt with this research.

  16. Augmented Reality Repair Guidance System

    Directory of Open Access Journals (Sweden)

    Sidharth Bhatia

    2012-07-01

    Full Text Available The daily life of a common man revolves around various forms of appliances/gadgets he uses throughout the day such as a mobile phone, laptop, printer, microwave oven, washing machine, etc. Although these appliances/gadgets are taken by most of the people for granted, the problem occurs when any of these things do not work as they are expected to. Getting them to the repair shops for every small glitch is expensive as well as time consuming. Although most of the companies which produce these appliances/gadgets do supply them with basic manuals, which deal with how to solve these minor issues, but reading them and at the same time repairing the corresponding appliance/gadget can be a frustrating task at times. These problems can be reduced to a large extent if some kind of live guidance is available. In this paper we propose a method to do so with the help of an augmented reality based system that will guide the user to carry out small scale repair jobs on these gadgets. All that is required is a decent webcam and a computing device, with a processor of 1 GHz or more and a display screen.

  17. Malignancy after gastrointestinal augmentation in childhood.

    Science.gov (United States)

    Husmann, Douglas A

    2009-04-01

    To review the incidence and risks of bladder cancer following gastrointestinal augmentations done for congenial anomalies in childhood. A literature search using PubMed and Ovid Medline search engines was performed. MeSH terms evaluated were; bladder augmentations, enterocystoplasty, gastrocystoplasty, spina bifida, spinal dysraphism, myelodysplasia, neural tube defects, posterior urethral valves and bladder exstrophy were cross referenced with the terms, bladder cancer and urinary bladder neoplasm. All patients who developed a bladder cancer following a bladder augmentation for a congenital anomaly were reviewed. A total of 20 cases of bladder cancer following augmentations for congential anomalies, were identified, 9 arose following ileal cystoplasty, 3 following colocystolasty and 8 following gastrocystoplasty. The incidence of cancer developing per decade following surgery was 1.5% for ileal/colonic and 2.8% for gastric bladder augmentations. The majority of cancers developing within the augmented bladder are at advanced stages at the time of diagnosis (60%; 12/20 cases were ≥T3 at diagnosis). Several of the cases that developed occurred in patients exposed to known carcinogenic stimuli and/or arose in bladders with a known predisposition to carcinoma. Patients augmented with ileal or colonic segment for a congenital bladder anomaly have a 7-8 fold and gastric augments a 14-15 fold increased risk for the development of bladder cancer over standard norms. Published data is however unable to determine if gastrointestinal bladder augmentation is an independent risk factor for cancer over the inherent risk of cancer arising from a congenitally abnormal bladder.

  18. Astrocytes in the nucleus of the solitary tract are activated by low glucose or glucoprivation: evidence for glial involvement in glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    David Harry McDougal

    2013-12-01

    Full Text Available Glucose homeostasis is maintained through interplay between central and peripheral control mechanisms which are aimed at storing excess glucose following meals and mobilizing these same stores during periods of fasting. The nucleus of the solitary tract (NST in the dorsal medulla has long been associated with the central detection of glucose availability and the control of glucose homeostasis. Recent evidence has emerged which supports the involvement of astrocytes in glucose homeostasis. The aim of the present study was to investigate whether NST-astrocytes respond to physiologically relevant decreases in glucose availability, in vitro, as well as to the presence of the glucoprivic compound 2-deoxy-D-Glucose. This report demonstrates that some NST-astrocytes are capable of responding to low glucose or glucoprivation by increasing cytoplasmic calcium; a change that reverses with restoration of normal glucose availability. While some NST-neurons also demonstrate an increase in calcium signaling during low glucose availability, this effect is smaller and somewhat delayed compared to those observed in adjacent astrocytes. TTX did not abolish these hypoglycemia mediated responses of astrocytes, suggesting that NST-astrocytes may be directly sensing low glucose levels as opposed to responding to neuronal detection of hypoglycemia. Thus, chemodetection of low glucose by NST-astrocytes may play an important role in the autonomic regulation of glucose homeostasis.

  19. Evidence-Based Medicine: Breast Augmentation.

    Science.gov (United States)

    Schwartz, Michael R

    2017-07-01

    After reading this article, the participant should be able to: 1. Understand the key decisions in patient evaluation for cosmetic breast augmentation. 2. Cite key decisions in preoperative planning. 3. Discuss the risks and complications, and key patient education points in breast augmentation. Breast augmentation remains one of the most popular procedures in plastic surgery. The integral information necessary for proper patient selection, preoperative assessment, and surgical approaches are discussed. Current data regarding long term safety and complications are presented to guide the plastic surgeon to an evidence-based approach to the patient seeking breast enhancement to obtain optimal results.

  20. Determination of student opinions in augmented reality

    Directory of Open Access Journals (Sweden)

    Huseyin Bicen

    2016-11-01

    Full Text Available The rapid development of the new technology has changed classroom teaching methods and tools in a positive way. This study investigated the classroom learning with augmented reality and the impact of student opinions. 97 volunteer undergraduate students took part in this study. Results included data in the form of frequencies, percentages and descriptive statistics. The results show that, with gamification methods, augmented reality content affected students’ opinions in a positive way. When QR codes are used in the classroom, students feel independent from classroom materials and can access various resources. Moreover, students think that, when augmented reality in the classroom is used, education is more enjoyable.

  1. Augmented Reality in Architecture: Rebuilding Archeological Heritage

    Science.gov (United States)

    de la Fuente Prieto, J.; Castaño Perea, E.; Labrador Arroyo, F.

    2017-02-01

    With the development in recent years of augmented reality and the appearance of new mobile terminals and storage bases on-line, we find the possibility of using a powerful tool for transmitting architecture. This paper analyzes the relationship between Augmented Reality and Architecture. Firstly, connects the theoretical framework of both disciplines through the Representation concept. Secondly, describes the milestones and possibilities of Augmented Reality in the particular field of archaeological reconstruction. And lastly, once recognized the technology developed, we face the same analysis from a critical point of view, assessing their suitability to the discipline that concerns us is the architecture and within archeology.

  2. Treatment algorithm of galactorrhea after augmentation mammoplasty.

    Science.gov (United States)

    Yang, Eun-Jung; Lee, Kyeong Tae; Pyon, Jai-Kyong; Bang, Sa-Ik

    2012-09-01

    Galactorrhea is a known complication of breast surgery, particularly reduction mammoplasty. However, in augmentation mammoplasty, it is a rare event. There are only a few case reports concerning galactorrhea after augmentation mammoplasty. In this report, we present a case of galactorrhea that occurred at 2 weeks postoperatively in a 34-year-old woman who had undergone augmentation mammoplasty with silicone implants via a transaxillary approach. Endocrinologic tests including serum prolactin level, routine blood work, and breast ultrasonography were all normal. The authors decided to manage conservatively with close observation. After 1 month, the symptom resolved without sequelae, and no recurrence has been reported.

  3. The protective effects of endogenous hydrogen sulfide modulator, S-propargyl-cysteine, on high glucose-induced apoptosis in cardiomyocytes: A novel mechanism mediated by the activation of Nrf2.

    Science.gov (United States)

    Yang, Hebei; Mao, Yicheng; Tan, Bo; Luo, Shanshan; Zhu, Yizhun

    2015-08-15

    S-propargyl-cysteine (SPRC) is a novel synthetic molecule exerting antioxidant effects via elevating generation of endogenous H2S. Our study aimed to elucidate possible antioxidant mechanisms of SPRC in hyperglycemia-induced oxidative stress. H9C2 cells were treated with SPRC or NaHS at the indicated concentration before being treated with high glucose for 48h. Follow-up experiments were based on detailed description given in Section 2. SD rats were injected with Streptozocin (STZ) to induce diabetes as previously reported. Diabetic rats were administrated with SPRC, NaHS or solution respectively for one week before the rats were killed for follow-up experiments. Our work found that SPRC remarkably attenuated high glucose induced generation of reactive oxygen species and apoptosis in H9C2 cells. SPRC increased stability and nuclear translocation of Nuclear factor erythroid 2-related factor 2 (Nrf2), up-regulated expression of antioxidant enzyme superoxide dismutase (SOD) and interfered with the interaction between Kelch-like ECH-associated protein 1 (KEAP1) and Nrf2. SPRC activated Nrf2 via Cystathionase-γ-lyase (CSE) and Akt pathway. CSE inhibitor PAG and Akt inhibitor LY294002 could reverse the protective effects of SPRC. Knockdown of Nrf2 by shRNA also blocked SPRC up-regulated expression of CSE. Similar results of protein expression and hypoglycemic activity of SPRC were observed in STZ induced diabetic rats.

  4. Glucose transporter 1 localisation throughout pregnancy in the carnivore placenta

    DEFF Research Database (Denmark)

    Wooding, F.B.P.; Dantzer, Vibeke; Klisch, K.

    2007-01-01

    Glucose is one of the major fetal nutrients. Maternofetal transfer requires transport across the several placental membranes. This transfer is mediated by one or more of the fourteen known isoforms of glucose transporter. So far only Glucose Transporters 1 and 3 (GT1, GT3) have been shown...... to be located in placental membranes. GT1 may be the only one on the syncytiotrophoblast (human) or both may be present on the same membrane (rodents) or be required in sequence (ruminants, horses and elephant). This paper shows GT1 to be the only transporter demonstrable by immunocytochemistry in carnivore...

  5. The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing.

    Directory of Open Access Journals (Sweden)

    Pia V Röder

    Full Text Available Intestinal glucose absorption is mediated by SGLT1 whereas GLUT2 is considered to provide basolateral exit. Recently, it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion. Moreover, SGLT1 and GLUT2 are suggested to play an important role in intestinal glucose sensing and incretin secretion. In mice that lack either SGLT1 or GLUT2 we re-assessed the role of these transporters in intestinal glucose uptake after radiotracer glucose gavage and performed Western blot analysis for transporter abundance in apical membrane fractions in a comparative approach. Moreover, we examined the contribution of these transporters to glucose-induced changes in plasma GIP, GLP-1 and insulin levels. In mice lacking SGLT1, tissue retention of tracer glucose was drastically reduced throughout the entire small intestine whereas GLUT2-deficient animals exhibited higher tracer contents in tissue samples than wild type animals. Deletion of SGLT1 resulted also in reduced blood glucose elevations and abolished GIP and GLP-1 secretion in response to glucose. In mice lacking GLUT2, glucose-induced insulin but not incretin secretion was impaired. Western blot analysis revealed unchanged protein levels of SGLT1 after glucose gavage. GLUT2 detected in apical membrane fractions mainly resulted from contamination with basolateral membranes but did not change in density after glucose administration. SGLT1 is unequivocally the prime intestinal glucose transporter even at high luminal glucose concentrations. Moreover, SGLT1 mediates glucose-induced incretin secretion. Our studies do not provide evidence for GLUT2 playing any role in either apical glucose influx or incretin secretion.

  6. BID Mediates Oxygen-Glucose Deprivation-Induced Neuronal Injury in Organotypic Hippocampal Slice Cultures and Modulates Tissue Inflammation in a Transient Focal Cerebral Ischemia Model without Changing Lesion Volume

    DEFF Research Database (Denmark)

    Martin, Nellie Anne; Bonner, Helena; Elkjær, Maria Louise

    2016-01-01

    The BH3 interacting-domain death agonist (BID) is a pro-apoptotic protein involved in death receptor-induced and mitochondria-mediated apoptosis. Recently, it has also been suggested that BID is involved in the regulation of inflammatory responses in the central nervous system. We found that BID ...

  7. Resonant Behavior of an Augmented Railgun

    CERN Document Server

    Bahder, Thomas B

    2011-01-01

    We consider a lumped circuit model of an augmented electromagnetic railgun that consists of a gun circuit and an augmentation circuit that is inductively coupled to the gun circuit. The gun circuit is driven by a d.c. voltage generator, and the augmentation circuit is driven by an a.c. voltage generator. Using sample parameters, we numerically solve the three non-linear dynamical equations that describe this system. We find that there is a resonant behavior in the armature kinetic energy as a function of the frequency of the voltage generator in the augmentation circuit. This resonant behavior may be exploited to increase armature kinetic energy. Alternatively, if the presence of the kinetic energy resonance is not taken into account, parameters may be chosen that result in less than optimal kinetic energy and efficiency.

  8. Augmenting the Web through Open Hypermedia

    DEFF Research Database (Denmark)

    Bouvin, N.O.

    2003-01-01

    Based on an overview of Web augmentation and detailing the three basic approaches to extend the hypermedia functionality of the Web, the author presents a general open hypermedia framework (the Arakne framework) to augment the Web. The aim is to provide users with the ability to link, annotate, a......, and otherwise structure Web pages, as they see fit. The paper further discusses the possibilities of the concept through the description of various experiments performed with an implementation of the framework, the Arakne Environment......Based on an overview of Web augmentation and detailing the three basic approaches to extend the hypermedia functionality of the Web, the author presents a general open hypermedia framework (the Arakne framework) to augment the Web. The aim is to provide users with the ability to link, annotate...

  9. ARC Code TI: ROC Curve Code Augmentation

    Data.gov (United States)

    National Aeronautics and Space Administration — ROC (Receiver Operating Characteristic) curve Code Augmentation was written by Rodney Martin and John Stutz at NASA Ames Research Center and is a modification of ROC...

  10. Augmented Reality Simulations on Handheld Computers

    Science.gov (United States)

    Squire, Kurt; Klopfer, Eric

    2007-01-01

    Advancements in handheld computing, particularly its portability, social interactivity, context sensitivity, connectivity, and individuality, open new opportunities for immersive learning environments. This article articulates the pedagogical potential of augmented reality simulations in environmental engineering education by immersing students in…

  11. Evaluating Human Factors in Augmented Reality Systems

    Science.gov (United States)

    2005-12-01

    user’s location and then per- forming the (cognitive) task of Mark A. Livingston Naval Research Laboratory Evaluating Human Factors in Augmented Reality ...00-00-2005 4. TITLE AND SUBTITLE Evaluating Human Factors in Augmented Reality Systems 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...the basis for situation awareness or—in combina- tion with visual cues—a navigation task. Tactile tasks. Via haptic devices, we can apply vir- tual

  12. Five features for modelling augmented reality

    OpenAIRE

    Liang, Sha; Roast, Chris

    2014-01-01

    Augmented reality is growing rapidly and supports people in differ-ent fields such as education, design, navigation and medicine. However, there is limited discussion about the characteristic features of augmented reality and what is meant by the term. This paper presents five different features: changea-bility, synchronicity and instant, antecedent, partial one to one and hidden reali-ty. The explanation of each of these features is given follow a consistent struc-ture. The benefits of gener...

  13. The Development of Mobile Augmented Reality

    Science.gov (United States)

    2012-01-01

    This chapter provides a high-level overview of fifteen years of augmented reality research that was sponsored by the U.S. Office of Naval Research...years by a number of university and industrial research laboratories. It laid the groundwork for the development of many commercial mobile augmented ... reality (AR) applications that are currently available for smartphones and tablets. Furthermore, it helped shape a number of ongoing research activities in mobile AR.

  14. Glucose effectiveness in nondiabetic relatives

    DEFF Research Database (Denmark)

    Egede, M B; Henriksen, J-E; Durck, T T;

    2014-01-01

    AIMS: Reduced glucose effectiveness is a predictor of future glucose tolerance in individuals with a family history of type 2 diabetes. We examined retrospectively at 10 years in normoglycemic relatives of diabetic subjects (RELs) the pathophysiological role of glucose effectiveness...... in the development of isolated impaired fasting glucose, glucose intolerance, and acute insulin release. METHODS: At 0 years, 19 RELs and 18 matched control subjects had glucose effectiveness (GE), insulin sensitivity, acute insulin release (AIR)IVGTT, and disposition index measured during an iv glucose tolerance...... test (IVGTT), using the minimal model analysis. At 0 and 10 years, oral glucose tolerance (OGTT) and AIROGTT were determined. RESULTS: At 0 years, fasting glucose (FG) and GE were raised in RELs, but insulin sensitivity and AIROGTT were reduced (P ≤ .05) compared with controls. At 10 years, RELs...

  15. MicroRNA-29a is up-regulated in beta-cells by glucose and decreases glucose-stimulated insulin secretion

    DEFF Research Database (Denmark)

    Bagge, Annika; Clausen, Trine R; Larsen, Sylvester;

    2012-01-01

    Chronically elevated levels of glucose impair pancreatic beta-cell function while inducing beta-cell proliferation. MicroRNA-29a (miR-29a) levels are increased in several tissues in diabetic animals and mediate decreased insulin-stimulated glucose-transport of adipocytes. The aim was to investiga...

  16. The HART I augmented electric gun facility

    Energy Technology Data Exchange (ETDEWEB)

    Fikse, D.A.; Ciesar, J.A.; Wehrli, H.A.; Rimersma, H.; Docherty, E.F.; Pipich, C.W. (Westinghouse Science and Technology Center, Pittsburgh, PA (US))

    1991-01-01

    This paper reports on an augmented electric gun system that has been commissioned. This system, called HART I (Hypervelocity Augmented Railgun Test), is built around a double augmented rail arrangement with a 1.27-cm square bore. It is powered by the SUVAC II 5.6-MJ distributed capacitor power supply. This arrangement allows operation in a simple, series augmented, or transaugmented gun system configuration. The objective of this facility is to perform materials research augmentation studies, and armature development in the 10-km/s regime. Armature masses of 2 to 4 g will be accelerated in a 4-m long barrel. Baseline bore materials will begin with conventional G9/GlidCop systems and then move into pyrolytic boron nitride/refractory materials. Hybrids, plasma, and ablation stabilized armature systems are planned. The gun system is instrumented with plasma and rail B-dot probes for inbore velocity measurements. In addition, breech and muzzle voltages, currents, and external velocities are measured. The HART I system is currently performing hypervelocity experiments to verify the augmentation models.

  17. Sweet taste receptor in the hypothalamus: a potential new player in glucose sensing in the hypothalamus.

    Science.gov (United States)

    Kohno, Daisuke

    2017-07-01

    The hypothalamic feeding center plays an important role in energy homeostasis. The feeding center senses the systemic energy status by detecting hormone and nutrient levels for homeostatic regulation, resulting in the control of food intake, heat production, and glucose production and uptake. The concentration of glucose is sensed by two types of glucose-sensing neurons in the feeding center: glucose-excited neurons and glucose-inhibited neurons. Previous studies have mainly focused on glucose metabolism as the mechanism underlying glucose sensing. Recent studies have indicated that receptor-mediated pathways also play a role in glucose sensing. This review describes sweet taste receptors in the hypothalamus and explores the role of sweet taste receptors in energy homeostasis.

  18. The Effect of Noscapine on Oxygen-Glucose Deprivation on Primary Murine Cortical Neurons in High Glucose Condition.

    Science.gov (United States)

    Vahabzadeh, Gelareh; Ebrahimi, Soltan-Ahmed; Rahbar-Roshandel, Nahid; Mahmoudian, Massoud

    2016-01-01

    In the present work we set out to investigate the neuroprotective effects of noscapine (0.5-2 µM) in presence of D-glucose on primary murine foetal cortical neurons after oxygen-glucose deprivation/24 h. recovery. Cell viability, nitric oxide production and intracellular calcium ((ca(2+))i) levels were evaluated by MTT assay, the modified Griess method and Fura-2 respectively. 25 and 100 mM D-glucose could, in a concentration dependent manner, improve cell viability and decrease NO production and (ca(2+))i level in neuronal cells after ischemic insult. Moreover, pre-incubation of cells with noscapine, noticeably enhanced protective effects of 25 and 100 mM D-glucose compared to similar conditions without noscapine pre-treatment. In fact, noscapine attenuated NO production in a dose-dependent fashion, after 30 minutes (min) OGD, during high-glucose (HG) condition in cortical neurons. Pretreatment with 2 μM noscapine and 25 or 100 mM D-glucose, was shown to decrease the rise in (ca(2+))i induced by Sodium azide/glucose deprivation (chemical OGD) model. These effects were more pronounced than that of 25 or 100 mM D-glucose alone. The present study demonstrated that the neuroprotective effects of HG before an ischemic insult were augmented by pre-treatment with noscapine. Our results also suggested that the neuroprotection offered by both HG and noscapine involve attenuation of NO production and (ca(2+))i levels stimulated by the experimental ischemia in cortical neurons.

  19. Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle

    DEFF Research Database (Denmark)

    Glund, Stephan; Deshmukh, Atul; Long, Yun Chau

    2007-01-01

    suggested to promote insulin-mediated glucose utilization. In this study, we determined the direct effects of IL-6 on glucose transport and signal transduction in human skeletal muscle. Skeletal muscle strips were prepared from vastus lateralis biopsies obtained from 22 healthy men. Muscle strips were...... incubated with or without IL-6 (120 ng/ml). We found that IL-6 increased glucose transport in human skeletal muscle 1.3-fold (P ... exposure increases glucose metabolism in resting human skeletal muscle. Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure....

  20. Enhanced muscle glucose metabolism after exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Garetto, L P; Goodman, M N

    1984-01-01

    Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase in the pr......Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase...... in the presence of insulin is found. To determine whether these alterations and in particular those mediated by insulin are due to local or systemic factors, one hindlimb of an anesthetized rat was electrically stimulated, and both hindlimbs were perfused immediately thereafter. Glucose and glycogen metabolism...... in the stimulated leg closely mimicked that observed previously after voluntary exercise on a treadmill. With no insulin added to the perfusate, glucose incorporation into glycogen was markedly enhanced in muscles that were glycogen depleted as were the uptake of 2-deoxyglucose and 3-O-methylglucose. Likewise...