24 results on '"Tomas, Eva"'
Search Results
2. Cuidados en los últimos días de vida en los pacientes hospitalizados en medicina interna
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Díez-Manglano, Jesús, Isasi de Isasmendi Pérez, Soledad, Rubio Gómez, Marta, Martín Pérez, Magdalena, Díez García, Luis Felipe, Vallejo Maroto, Ignacio, Ocaña Losada, Cristina, Giner Escobar, Pilar, Díaz Pérez, Catalina, Caballero Granado, Javier, García Font, Resfa María, Jódar Lorente, Francisco J., Pérez Vázquez, Gloria, Ferro Expósito, Ana Belén, Amaya González, María Luisa, Gamboa Antiñolo, Fernando, González Molina, Álvaro, Gómez Hernández, Mercedes, Guzmán García, Marcos, Benítez León, Lola, Montero Rivas, Lorena, Ruiz Mariscal, María, Gómez Aguirre, Noelia, González García, María Pilar, Martín Algora, Isabel, Bueno Castel, María Carmen, Ruiz Laiglesia, Fernando, Bejarano Tello, Esperanza, Cabrerizo García, José Luis, Guiral Fernández, Nuria, Camera, Luis, Gauna, Carla, Abad Requejo, Pedro, Martínez Gutiérrez, Rocío, Fernández Regueiro, Rebeca, Sánchez Vidal, María Teresa, Alfonso Mejido, Joaquín, García Carús, Enrique, Calvo Rodríguez, Carmen Elena, Martínez García, Paula, Ruiz Olivares, Sixto, Fullana Barcelo, María Isabel, González Arencibia, Carmen, Ros Vilamajó, Rosa, Monedero Prieto, María José, González Becerra, Concepción, Pérez, Sofía, Martín Plata, Andrea, Portilla Chocarro, Raquel, Dueñas Gutiérrez, Carlos, Estrada Álvarez, Francisco, Peña Balbuena, Sonia, Rodríguez Galindo, Raúl, Cobos Siles, Marta María, Sánchez Muñoz, Luis Ángel, Castañón López, Ana, Sanz Lobo, Celia, Chimeno Viñas, María Montserrat, Contreras Uriel, María Ángeles, Gil Domínguez, Judit, Medrano González, Francisco, Machín Lázaro, José Manuel, Magallanes Gamboa, Jeffrey, Rodríguez Galdeano, Mónica, Castro Giménez, Joaquín, Barberá Farré, José Ramón, Núñez Aragón, Raquel, Masanés Torán, Ferrán, Barbé, José, Güell Farré, Elena, Torres Bonafonte, Olga, Lozano Miñana, Ana, Moras Sarabia, Desirée, Pérez, Rosa, Arnau i Fernández, Dolors, Formiga, Francesc, Fernández Fernández, Javier, Castro Salomó, Antoni, Qanneta, Rami, Pardo Ortega, María Victoria, Estrada Díaz, Cristina, Monterroso Pintado, Yasmina, García Cors, Montserrat, Almendros Rivas, María Cruz, Domingo Albin, Dolors, Roig Morera, Jaume, Galofré Álvaro, Nuria, Toro Parodi, Aythami, Loureiro Sánchez, Mario, de la Guerra Acebal, Carla, Zubizarreta García, Javier, Benavente Claveras, Iasone, Martí Cabanes, Juan, Sanz Lázaro, Ignacio, Barquero Romero, José, Nevado López-Alegría, Leticia, Arévalo Lorido, José Carlos, Casariego Vales, Emilio, Lorenzo Vizcaya, Ana María, Macía Rodríguez, Cristina, Pérez Fernández, Silvia, Sesma Sánchez, Pascual, Jiménez-Beatty, María Dolores, González Vázquez, Laura, Brea Hernando, Ángel, Castiella Herrero, Jesús, González Anglada, María Isabel, Gracia Lorenzo, Virginia M., Pérez Martín, Alejandro, García Melcón, Gerardo, Gómez Antúnez, María, Quesada Simón, María Angustias, Gil Gil, Fuensanta, Asenjo Martínez, María, Mancebo Aragoneses, Lourdes, Calderón Parra, Jorge, Romero Pérez, María del Carmen, Curbelo García, José, Laguna Cuesta, Fernando, Segovia Abad, María Eugenia, Fontecha Ortega, María, Lara Martínez, Guillermina, Pinos Blanco, Ana, Rodil Fraile, Raquel, Martínez Litago, Elisabel, Echeverría Echeverría, Aitziber, Priego Valladares, Manuel, Trescoli Serrano, Carlos, Vicente Mas, Josep, Torregrosa Suau, Óscar, Gil Tomás, Eva, Castillo Rubio, Rafael, Murcia Zaragoza, José Manuel, Román Sánchez, Pilar, García Herola, Ana, Tenllado Doblas, Pedro Pablo, Blázquez Encinar, Julio César, Castellano Vela, Enrique, Carrizo, Néstor, Giner Galvañ, Vicente, Roca Villanueva, Bernardino Manuel, Pasquau Liaño, Francisco, Pascual Izuel, José María, Díez-Manglano, J., Isasi de Isasmendi Pérez, S., Rubio Gómez, M., Formiga, F., Sánchez Muñoz, L.Á., Castiella Herrero, J., Casariego Vales, E., and Torres Bonafonte, O.H.
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- 2019
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3. Enhanced Muscle Fat Oxidation and Glucose Transport by ACRP30 Globular Domain: Acetyl-CoA Carboxylase Inhibition and AMP-Activated Protein Kinase Activation
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Tomas, Eva, Tsao, Tsu-Shuen, Saha, Asish K., Murrey, Heather E., Zhang, Cheng cheng, Itani, Samar I., Lodish, Harvey F., and Ruderman, Neil B.
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- 2002
4. Mortality Risk in Alcoholic Patients in Northern Italy: Comorbidity and Treatment Retention Effects in a 30-Year Follow-Up Study
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Morandi, Gianni, Periche Tomas, Eva, and Pirani, Monica
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- 2016
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5. Insulin-like actions of glucagon-like peptide-1: a dual receptor hypothesis
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Tomas, Eva and Habener, Joel F.
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- 2010
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6. GLP-1(32-36)amide Pentapeptide Increases Basal Energy Expenditure and Inhibits Weight Gain in Obese Mice
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Tomas, Eva, Stanojevic, Violeta, McManus, Karen, Khatri, Ashok, Everill, Paul, Bachovchin, William W., and Habener, Joel F.
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- 2015
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7. GLP-1(32–36)amide, a novel pentapeptide cleavage product of GLP-1, modulates whole body glucose metabolism in dogs
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Elahi, Dariush, Angeli, Franca S., Vakilipour, Amin, Carlson, Olga D., Tomas, Eva, Egan, Josephine M., Habener, Joel F., and Shannon, Richard P.
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- 2014
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8. Palliative Sedation in Patients Hospitalized in Internal Medicine Departments
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Díez-Manglano, Jesús, de Isasmendi Pérez, Soledad Isasi, Gómez, Marta Rubio, Pérez, Magdalena Martín, Díez García, Luis Felipe, Maroto, Ignacio Vallejo, Losada, Cristina Ocaña, Roldán, Susana Moya, Pérez, Catalina Díaz, Granado, Javier Caballero, García Font, Resfa María, Jódar Lorente, Francisco J., Vázquez, Gloria Pérez, Expósito, Ana belén Ferro, Amaya González, María Luisa, Antiñolo, Fernando Gamboa, Molina, Álvaro González, Hernández, Mercedes Gómez, García, Marcos Guzmán, León, Lola Benítez, Rivas, Lorena Montero, Mariscal, María Ruiz, Aguirre, Noelia Gómez, González García, María Pilar, Algora, Isabel Martín, Bueno Castel, María Carmen, Laiglesia, Fernando Ruiz, Tello, Esperanza Bejarano, Cabrerizo García, José Luis, Fernández, Nuria Guiral, Camera, Luis, Gauna, Carla, Requejo, Pedro Abad, Gutiérrez, Rocío Martínez, Regueiro, Rebeca Fernández, Sánchez Vidal, María Teresa, Mejido, Joaquín Alfonso, Carús, Enrique García, Calvo Rodríguez, Carmen Elena, García, Paula Martínez, Olivares, Sixto Ruiz, Fullana Barcelo, María Isabel, Arencibia, Carmen González, Vilamajó, Rosa Ros, José Monedero Prieto, María, Becerra, Concepción González, Pérez, Sofía, Plata, Andrea Martín, Chocarro, Raquel Portilla, Gutiérrez, Carlos Dueñas, Álvarez, Francisco Estrada, Balbuena, Sonia Peña, Galindo, Raúl Rodríguez, Cobos Siles, Marta María, Sánchez Muñoz, Luis Ángel, López, Ana Castañón, Lobo, Celia Sanz, Chimeno Viñas, María Montserrat, Contreras Uriel, María Ángeles, Domínguez, Judit Gil, González, Francisco Medrano, Machín Lázaro, José Manuel, Gamboa, Jeffrey Magallanes, Galdeano, Mónica Rodríguez, Giménez, Joaquín Castro, Barberá Farré, José Ramón, Aragón, Raquel Núñez, Torán, Ferrán Masanés, Barbé, José, Farré, Elena Güell, Bonafonte, Olga Torres, Miñana, Ana lozano, Sarabia, Desirée Moras, Pérez, Rosa, Arnau i Fernández, Dolors, Formiga, Francesc, Fernández, Javier Fernández, Salomó, Antoni Castro, Qanneta, Rami, Pardo Ortega, María Victoria, Díaz, Cristina Estrada, Pintado, Yasmina Monterroso, Cors, Montserrat García, Almendros Rivas, María Cruz, Albin, Dolors Domingo, Morera, Jaume Roig, Álvaro, Nuria Galofré, Parodi, Aythami Toro, Sánchez, Mario Loureiro, Acebal, Carla de la Guerra, García, Javier Zubizarreta, Claveras, Iasone Benavente, Cabanes, Juan Martí, Lázaro, Ignacio Sanz, Romero, José Barquero, López-Alegría, Leticia Nevado, Arévalo Lorido, José Carlos, Vales, Emilio Casariego, Lorenzo Vizcaya, Ana María, Rodríguez, Cristina Macía, Fernández, Silvia Pérez, Sánchez, Pascual Sesma, Jiménez-Beatty, María Dolores, Vázquez, Laura González, Hernando, Ángel Brea, Herrero, Jesús Castiella, González Anglada, María Isabel, Gracia Lorenzo, Virginia M., Martín, Alejandro Pérez, Melcón, Gerardo García, Antúnez, María Gómez, Quesada Simón, María Angustias, Gil, Fuensanta Gil, Martínez, María Asenjo, Aragoneses, Lourdes Mancebo, Parra, Jorge Calderón, Pérez, María del Carmen Romero, García, José Curbelo, Cuesta, Fernando Laguna, Segovia Abad, María Eugenia, Ortega, María Fontecha, Martínez, Guillermina Lara, Blanco, Ana Pinos, Fraile, Raquel Rodil, Litago, Elisabel Martínez, Echeverría, Aitziber Echeverría, Valladares, Manuel Priego, Serrano, Carlos Trescoli, Mas, Josep Vicente, Suau, Óscar Torregrosa, Tomás, Eva Gil, Rubio, Rafael Castillo, Murcia Zaragoza, José Manuel, Sánchez, Pilar Román, Herola, Ana García, Tenllado Doblas, Pedro Pablo, Blázquez Encinar, Julio César, Vela, Enrique Castellano, Carrizo, Néstor, Galvañ, Vicente Giner, Roca Villanueva, Bernardino Manuel, Liaño, Francisco Pasquau, Pascual Izuel, José María, Isasi de Isasmendi Pérez, Soledad, García Fenoll, Rosa, Sánchez, Luis Ángel, Formiga, Françesc, Giner Galvañ, Vicente, Dueñas, Carlos, Roca, Bernardino, Estrada Díaz, Cristina, and Casariego Vales, Emilio
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- 2020
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9. Thiazolidinediones can rapidly activate AMP-activated protein kinase in mammalian tissues
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LeBrasseur, Nathan K., Kelly, Meghan, Tsao, Tsu-Shuen, Farmer, Stephen R., Saha, Asish K., Ruderman, Neil B., and Tomas, Eva
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Enzymes -- Research ,Insulin -- Research ,Diabetes -- Research ,Metabolism -- Research ,Biological sciences - Abstract
Thiazolidinediones (TZDs) are insulin-sensitizing agents used in the treatment of type 2 diabetes. A widely held view is that their action is secondary to transcriptional events that occur when TZDs bind to the nuclear receptor PPAR[gamma] in the adipocyte and stimulate adipogenesis. It has been proposed that this increases insulin sensitivity, at least in part, by increasing the expression and release of adiponectin, an adipokine that activates the fuel-sensing enzyme AMP-activated protein kinase (AMPK). In this study, we report that TZDs also acutely activate AMPK in skeletal muscle and other tissues by a mechanism that is likely independent of PPAR[gamma]-regulated gene transcription. Thus incubation of isolated rat EDL muscles in medium containing 5 [micro]M troglitazone for 15 min (too brief to be attributable to transcription) significantly increased pAMPK and pACC. At a concentration of 100 [micro]M, troglitazone maximally increased these parameters and caused twofold increases in 2-deoxy-D-glucose uptake and the oxidation of exogenous [[sup.14]C]palmitate. Time course studies revealed that troglitazone-induced increases in pAMPK and pACC abundance at 15 min were paralleled by an increase in the AMP-to-ATP ratio and that by 60 min all of these parameters had returned to baseline values. Increases in pAMPK and pACC were also observed in skeletal muscle, liver, and adipose tissue in intact rats 15 min after the administration of a single dose of troglitazone (10 mg/kg, ip). Likewise, troglitazone and another TZD, pioglitazone, caused rapid increases in pAMPK and pACC of equal magnitude in Swiss 3T3 fibroblasts with and without sufficient PPAR[gamma] to mediate the expression of target genes. The results indicate that TZDs can act within minutes to activate AMPK in mammalian tissues. They suggest that this effect is associated with a change in cellular energy state and that it is not dependent on PPAR[gamma]-mediated gene transcription. acetyl-coenzyme A carboxylase; adiponectin; diabetes; insulin sensitivity; metabolism
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- 2006
10. Diffusion-weighted MR spectroscopy (DW-MRS): A novel in-vivo method for imaging inflammation and age-associated changes in glial morphology
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Periche Tomas, Eva, Ronen, Itamar, Maclver, Claire, Sastin, Dmitri, Underwood, Jon, Coulson, James, Leach, Helena, Bone, Claudia, Cercignani, Mara, and Harrison, Neil
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- 2022
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11. CaMKK Is a Regulator of AMPK Activation by Adiponectin: Studies in C2C12 Myocytes and HepG2 Cells: 52-OR
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TOMAS, EVA, TSAO, TSU-SHUEN, SAHA, ASISH K., LODISH, HARVEY F., and RUDERMAN, NEIL B.
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- 2006
12. Metabolic and hormonal interactions between muscle and adipose tissue
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Tomas, Eva, Kelly, Meghan, Xiang, Xiaoqin, Tsao, Tsu-Shuen, Keller, Charlotte, Keller, Pernille, Luo, Zhijun, Lodish, Harvey, Saha, Asish K., Unger, Roger, and Ruderman, Neil B.
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- 2004
13. AICAR Administration Causes an Apparent Enhancement of Muscle and Liver Insulin Action in Insulin-Resistant High-Fat-Fed Rats
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Iglesias, Miguel A., Ye, Ji-Ming, Frangioudakis, Georgia, Saha, Asish K., Tomas, Eva, Ruderman, Neil B., Cooney, Gregory J., and Kraegen, Edward W.
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- 2002
14. Developmental trajectories of metacognitive processing and executive function from childhood to older age.
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Filippi, Roberto, Ceccolini, Andrea, Periche-Tomas, Eva, and Bright, Peter
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BILINGUALISM ,EXPLORATORY factor analysis ,AGE groups ,METACOGNITION - Abstract
The modern understanding of the term metacognition encompasses two levels of processing: a lower level awareness or knowledge of one's own thoughts and a higher level regulation or control of our thinking. Metacognition, therefore, bears conceptual similarity with executive function: both are concerned with top-down monitoring and control of cognition in the service of ongoing goal-directed behaviour. Previous studies have shown a possible executive function advantage in multilingual speakers but also a possible disadvantage in metacognitive processing. To progress theory on metacognitive processing and the relationship with executive function and linguistic experience across the lifespan, we conducted a study testing 330 healthy individuals in four age groups from 7 to 80 years old. All participants performed a metacognition task and two measures of executive function, which included the Simon task and the Tower of London task. Half the participants were multilingual speakers since birth. We built developmental trajectories of metacognitive and executive function across the lifespan. The best metacognitive efficiency was observed in mid-adulthood, whereas the best executive function processing reached its peak in young adulthood. A steep cognitive decline was observed in older age, while metacognitive efficiency was preserved. Exploratory factor analysis indicated that metacognition and executive function are served by different factors across all ages. Contrary to previous findings in the bilingual literature, a multilinguistic experience conferred neither any significant advantage nor disadvantage in both executive function and metacognitive processing across the lifespan. [ABSTRACT FROM AUTHOR]
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- 2020
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15. A role for the cerebellum in the control of verbal interference: Comparison of bilingual and monolingual adults.
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Filippi, Roberto, Periche Tomas, Eva, Papageorgiou, Andriani, and Bright, Peter
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VOXEL-based morphometry , *INTERFERENCE (Linguistics) , *CEREBELLUM , *AGE groups , *ADULTS , *TASK performance - Abstract
We evaluate brain structure sensitivity to verbal interference in a sentence interpretation task, building on previously reported evidence that those with better control of verbal interference show higher grey matter density in the posterior paravermis of the right cerebellum. We compare brain structure sensitivity to verbal interference control across two groups, English monolingual (N = 41) and multilingual (N = 46) adults. Using voxel-based morphometry, our primary goal was to identify and explore differences in regional patterns of grey matter sensitivity to performance on the sentence interpretation task, controlling for group variability in age, nonverbal reasoning and vocabulary knowledge. There was no group difference in performance but there was a significant group effect in grey matter sensitivity to task performance in our region of interest: stronger sensitivity in the paravermis in bilinguals compared to monolinguals in accuracy performance in the high (relative to low) verbal interference condition. This effect was observed when the linguistic interference was presented in an unfamiliar language (Greek) but not when presented in the familiar language (English). Our findings suggest that multilanguage acquisition mediates regional involvement within the language network, conferring enhanced functional plasticity within structures (including the paravermis) in the service of control of linguistic interference. [ABSTRACT FROM AUTHOR]
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- 2020
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16. Evidence against a cognitive advantage in the older bilingual population.
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Papageorgiou, Andriani, Periche Tomas, Eva, Filippi, Roberto, and Bright, Peter
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RESPONSE inhibition , *MEMORY , *PROBLEM solving , *SHORT-term memory , *MONOLINGUALISM , *TASK performance , *EVIDENCE , *LANGUAGE ability - Abstract
Recent evidence has challenged long-standing claims that multi-language acquisition confers long-term advantages in executive function and may protect against age-related cognitive deterioration. We assessed evidence for a bilingual advantage in older monolingual and bilingual residents matched on age, gender, and socioeconomic status. A comprehensive battery of tests was administered to measure non-verbal reasoning, working memory capacity, visuo-spatial memory, response inhibition, problem solving, and language proficiency. Analyses, including Bayes factors, revealed comparable performance in both groups, with no significant differences on any task (and the only trend, found for the Tower of London task performance, indicated a monolingual advantage). Overall, therefore, our findings run counter to the bilingual advantage hypothesis. We consider the implications of our study and offer suggestions for future work in this area. [ABSTRACT FROM AUTHOR]
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- 2019
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17. The Importance of Socioeconomic Status as a Modulator of the Bilingual Advantage in Cognitive Ability.
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Naeem, Kamila, Filippi, Roberto, Periche-Tomas, Eva, Papageorgiou, Andriani, and Bright, Peter
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COGNITIVE ability ,EXECUTIVE function ,EXECUTIVE ability (Management) ,REACTION time ,ERROR rates ,TASK performance - Abstract
Between-group variability in socioeconomic status (SES) has been identified as a potentially important contributory factor in studies reporting cognitive advantages in bilinguals over monolinguals (the so called "bilingual advantage"). The present study addresses the potential importance of this alternative explanatory variable in a study of low and high SES bilingual and monolingual performance on the Simon task and the Tower of London (TOL) task. Results indicated an overall bilingual response time advantage on the Simon task, despite equivalent error rates. Socioeconomic status was an important modulator in this effect, with evidence that bilingualism may be particularly important in promoting speed of processing advantages in low status individuals but have little impact in high status individuals. However, there was a monolingual advantage on the TOL test of executive planning ability. Together, our findings run counter to the central assertion of the bilingual advantage account, that the process of multi-language acquisition confers a broad cognitive advantage in executive function. We discuss these findings in the context of SES as an important modulator in published studies advocating a bilingual cognitive advantage. [ABSTRACT FROM AUTHOR]
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- 2018
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18. GLP-1-derived nonapeptide GLP-1(28–36)amide inhibits weight gain and attenuates diabetes and hepatic steatosis in diet-induced obese mice
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Tomas, Eva, Wood, Jenna A., Stanojevic, Violeta, and Habener, Joel F.
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GLUCAGON-like peptide 1 , *INSULIN resistance , *OBESITY in animals , *WEIGHT gain , *DIABETES , *METABOLIC syndrome treatment , *LABORATORY mice , *ACTIVE oxygen in the body , *DIET in disease - Abstract
Abstract: Background: The metabolic syndrome is an obesity-associated disease manifested as severe insulin resistance, hyperlipidemia, hepatic steatosis, and diabetes. Previously we proposed that a nonapeptide, FIAWLVKGRamide, GLP-1(28–36)amide, derived from the gluco-incretin hormone, glucagon-like peptide-1 (GLP-1), might have insulin-like actions. Recently, we reported that the nonapeptide appears to enter hepatocytes, target to mitochondria, and suppress glucose production and reactive oxygen species. Therefore, the effects of GLP-1(28–36)amide were examined in diet-induced obese, insulin-resistant mice as a model for the development of human metabolic syndrome. Methods and results: Three- to 11-week infusions of GLP-1(28–36)amide were administered via osmopumps to mice fed a very high fat diet (VHFD) and to control mice on a normal low fat diet (LFD). Body weight, DXA, energy intake, plasma insulin and glucose, and liver triglyceride levels were assessed. GLP-1(28–36)amide inhibited weight gain, accumulation of liver triglycerides, and improved insulin sensitivity by attenuating the development of fasting hyperglycemia and hyperinsulinemia in mice fed VHFD. GLP-1(28–36)amide had no observable effects in control LFD mice. Surprisingly, the energy intake of peptide-infused obese mice is 25–70% greater than in obese mice receiving vehicle alone, yet did not gain excess weight. Conclusions: GLP-1(28–36)amide exerts insulin-like actions selectively in conditions of obesity and insulin resistance. The peptide curtails weight gain in diet-induced obese mice in the face of an increase in energy intake suggesting increased energy expenditure. These findings suggest utility of GLP-1(28–36)amide, or a peptide mimetic derived there from, for the treatment of insulin resistance and the metabolic syndrome. [Copyright &y& Elsevier]
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- 2011
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19. GLP-1-derived nonapeptide GLP-1(28–36)amide targets to mitochondria and suppresses glucose production and oxidative stress in isolated mouse hepatocytes
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Tomas, Eva, Stanojevic, Violeta, and Habener, Joel F.
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GLUCAGON-like peptide 1 , *MITOCHONDRIA , *GLUCONEOGENESIS , *OXIDATIVE stress , *LIVER cells , *METABOLIC syndrome , *INSULIN resistance , *LABORATORY mice , *PREVENTION - Abstract
Abstract: Background: Uncontrolled hepatic glucose production (gluconeogenesis), and glycogenolysis, is a major contributor to the fasting hyperglycemia associated with type 2 diabetes. Here we report the discovery of a C-terminal nonapeptide (FIAWLVKGRamide) derived from GLP-1 that suppresses glucose production and oxidative stress in isolated mouse hepatocytes. The nonapeptide, GLP-1(28–36)amide, was reported earlier to be a major product derived from the cleavage of GLP-1 by the endopeptidase NEP 24.11. Methods and results: Hepatocytes were isolated from the livers of normal and diet-induced obese mice. We find that the GLP-1(28–36)amide nonapeptide rapidly enters isolated mouse hepatocytes by GLP-1 receptor-independent mechanisms, and targets to mitochondria where it inhibits gluconeogenesis and oxidative stress. Conclusions: These findings suggest that GLP-1 not only acts on a cell surface G-protein coupled receptor activating kinase-regulated signaling pathways, but a small C-terminal peptide derived from GLP-1 also enters cells, targets mitochondria, and exerts insulin-like actions by modulating oxidative phosphorylation. GLP-1(28–36)amide, or a peptide mimetic derived there from, might prove to be a useful treatment for fasting hyperglycemia and metabolic syndrome in type 2 diabetes. [Copyright &y& Elsevier]
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- 2011
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20. AMP-activated protein kinase and its regulation by adiponectin and interleukin-6.
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Kelly, Meghan, Ruderman, Neil B., and Tomas, Eva
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ADENOSINE triphosphate ,INTERLEUKIN-6 ,METABOLIC syndrome ,FAT cells ,DIABETES ,LABORATORY mice - Abstract
AMP-activated protein kinase (AMPK) is a fuel-sensing enzyme that responds to decreases in cellular energy state by activating processes that generate adenosine triphosphate (ATP) (e.g. fatty acid oxidation), and inhibiting others that consume ATP but are not acutely necessary for survival (e.g. fatty acid, triglyceride and protein synthesis). In contrast, sustained decreases in AMPK or a failure to activate it appropriately have been implicated in the pathogenesis of the metabolic syndrome. Recent studies suggest that various hormones can activate or inhibit AMPK. One of these hormones, adiponectin (Adn), an adipokine released by the fat cell, activates AMPK in liver, muscle, primary rat adipocytes, cultured endothelium and almost certainly other cells. Low plasma levels of Adn are associated with the metabolic syndrome; thus, in both humans and experimental animals, they are often accompanied by obesity, insulin resistance, ectopic lipid deposition, and a predisposition to both type 2 diabetes and atherosclerotic heart disease. Recent studies suggest that thiazoledinediones (TZDs), agents used to treat diabetes because they diminish insulin resistance, exert this effect in great measure by increasing the synthesis and release of adiponectin by the adipocyte and secondarily increasing AMPK activity in the liver and other tissues. Another cytokine that has been shown to activate AMPK is interleukin-6 (IL-6). Studies in IL-6 knockout (KO) mice have revealed that AMPK activity is diminished in their muscle and adipose tissue at 3 months of age and that, like the adiponectin KO mice, they are predisposed to obesity, glucose intolerance and hypertriglyceridemia. Likewise, when bred on an Apo E–/– they develop more severe atherosclerosis than control mice. Whether AMPK activation by other means prevents the development of the metabolic syndrome in the IL-6 or adiponectin KO mice remains to be determined. [ABSTRACT FROM AUTHOR]
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- 2006
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21. Role of Disulfide Bonds in Acrp30/Adiponectin Structure and Signaling Specificity.
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Tsu-Shuen Tsao, Tomas, Eva, Murrey, Heather E., Hug, Christopher, Lee, David H., Ruderman, Neil B., Heuser, John E., and Lodish, Harvey F.
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SULFIDES , *CHEMICAL bonds , *BLOOD proteins , *LIPIDS , *GLUCOSE , *METABOLISM - Abstract
Acrp30/adiponectin is an adipocyte-derived serum protein with important roles in regulation of lipid and glucose metabolism, but which of its isoforms are biologically active remains controversial. We addressed this issue by first characterizing the structure of each individual Acrp30 oligomer and the determinants responsible for multimer formation. Freeze etch electron microscopy showed the trimer to exhibit a ball-and-stick-like structure containing a large globular sphere, an extended collagen stalk, and a smaller sphere on the opposite end of the stalk. The hexamer consists of two adjacent trimeric globular domains and a single stalk composed of collagen domains from two trimers. Although not necessary for trimer formation or stability, two of the three monomers in an Acrp30 trimer are covalently linked by a disulfide bond between cysteine residues at position 22. In contrast, assembly of hexameric and higher molecular weight (HMW) forms of Acrp30 depends upon formation of Cys[sup 22]-mediated disulfide bonds because their reduction with dithiothreitol or substitution of Cys[sup 22] with alanine led exclusively to trimers. HMW and hexamer isoforms of Acrp30 activated NF-κB in C2C12 cells, but trimers, either natural, formed by reduction of Acrp30 hexamer, or formed by the C22A mutant, did not. In contrast, incubation of isolated rat extensor digitorum longus with naturally formed Acrp30 trimers or trimeric C22A Acrp30 led to increased phosphorylation of AMP-activated protein kinase-α at Thr[sup 172] and its activation. Hexameric and HMW Acrp30 could not activate AMP-activated protein kinase. Thus, trimeric and HMW/hexameric Acrp30 activate different signal transduction pathways, and Acrp30 represents a novel example of the control of ligand signaling via changes in its oligomerization state. [ABSTRACT FROM AUTHOR]
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- 2003
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22. FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance.
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Bernardo, Barbara, Zhou, Yingjiang, Tomas, Eva M., Calle, Roberto A., Erion, Derek M., Rolph, Timothy P., Brenner, Martin, Talukdar, Saswata, Lu, Min, Bandyopadhyay, Gautam, Li, Pingping, Huang, Jie, and Levin, Nancy
- Subjects
LIVER ,BROWN adipose tissue ,GLUCOSE ,INSULIN ,LIPID synthesis - Abstract
FGF21 is a key metabolic regulator modulating physiological processes and its pharmacological administration improves metabolic profile in preclinical species and humans. We used native-FGF21 and a long-acting FGF21 (PF-05231023), to determine the contribution of liver and brown adipose tissue (BAT) towards metabolic improvements in Zucker rats and DIO mice (DIOs). FGF21 improved glucose tolerance and liver insulin sensitivity in Zuckers without affecting BW and improved liver function by decreased lipogenesis, increased fatty acid oxidation and improved insulin signaling. Through detailed lipidomic analyses of liver metabolites in DIOs, we demonstrate that FGF21 favorably alters liver metabolism. We observed a dose-dependent increase of [
18 F]-FDG-glucose uptake in interscapular BAT (iBAT) of DIOs upon FGF21 administration. Upon excision of iBAT (X-BAT) and administration of FGF21 to mice housed at 80 °F or 72 °F, the favorable effects of FGF21 on BW and glucose excursion were fully retained in both sham and X-BAT animals. Taken together, we demonstrate the liver as an organ that integrates the actions of FGF21 and provide metabolic benefits of FGF21 in Zucker rats and DIOs. Finally, our data demonstrates iBAT does not play a role in mediating favorable metabolic effects of FGF21 administration in DIOs housed at 80 °F or 72 °F. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
23. Mice Lacking Adiponectin Show Decreased Hepatic Insulin Sensitivity and Reduced Responsiveness to Peroxisome Proliferator-activated Receptor γ Agonists.
- Author
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Nawrocki, Andrea R., Rajala, Michael W., Tomas, Eva, Pajvani, Utpal B., Saha, Asish K., Trumbauer, Myrna E., Zhen Pang, Chen, Airu S., Ruderman, Neil B., Chen, Howard, Rossetti, Luciano, and Scherer, Philipp E.
- Subjects
- *
INSULIN resistance , *ADIPOSE tissues , *PROTEIN kinases , *DIAGNOSIS of diabetes , *GLUCOSE tolerance tests , *PEROXISOMES , *MICE - Abstract
The adipose tissue-derived hormone adiponectin improves insulin sensitivity and its circulating levels are decreased in obesity-induced insulin resistance. Here, we report the generation of a mouse line with a genomic disruption of the adiponectin locus. We aimed to identify whether these mice develop insulin resistance and which are the primary target tissues affected in this model. Using euglycemic/insulin clamp studies, we demonstrate that these mice display severe hepatic but not peripheral insulin resistance. Furthermore, we wanted to test whether the lack of adiponectin magnifies the impairments of glucose homeostasis in the context of a dietary challenge. When exposed to high fat diet, adiponectin null mice rapidly develop glucose intolerance. Specific PPARγ/agonists such as thiazolidinediones (TZDs) improve insulin sensitivity by mechanisms largely unknown. Circulating adiponectin levels are significantly up-regulated in vivo upon activation of PPARγ/. Both TZDs and adiponectin have been shown to activate AMP-activated protein kinase (AMPK) in the same target tissues. We wanted to address whether the ability of TZDs to improve glucose tolerance is dependent on adiponectin and whether this improvement involved AMPK activation. We demonstrate that the ability of PPARγ agonists to improve glucose tolerance in ob/ob mice lacking adiponectin is diminished. Adiponectin is required for the activation of AMPK upon TZD administration in both liver and muscle. In summary, adiponectin is an important contributor to PPARγ-mediated improvements in glucose tolerance through mechanisms that involve the activation of the AMPK pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
24. Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways.
- Author
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Tsao TS, Tomas E, Murrey HE, Hug C, Lee DH, Ruderman NB, Heuser JE, and Lodish HF
- Subjects
- Adiponectin, Alanine chemistry, Amino Acid Sequence, Animals, Blotting, Western, Cell Line, Chromatography, Gel, Cryoelectron Microscopy, Cysteine chemistry, Dimerization, Disulfides chemistry, Dithiothreitol pharmacology, Genes, Reporter, Humans, Ligands, Luciferases metabolism, Mice, Molecular Sequence Data, Muscles metabolism, Mutagenesis, Site-Directed, NF-kappa B metabolism, Protein Conformation, Protein Isoforms, Sequence Homology, Amino Acid, Intercellular Signaling Peptides and Proteins, Proteins chemistry, Signal Transduction
- Abstract
Acrp30/adiponectin is an adipocyte-derived serum protein with important roles in regulation of lipid and glucose metabolism, but which of its isoforms are biologically active remains controversial. We addressed this issue by first characterizing the structure of each individual Acrp30 oligomer and the determinants responsible for multimer formation. Freeze etch electron microscopy showed the trimer to exhibit a ball-and- stick-like structure containing a large globular sphere, an extended collagen stalk, and a smaller sphere on the opposite end of the stalk. The hexamer consists of two adjacent trimeric globular domains and a single stalk composed of collagen domains from two trimers. Although not necessary for trimer formation or stability, two of the three monomers in an Acrp30 trimer are covalently linked by a disulfide bond between cysteine residues at position 22. In contrast, assembly of hexameric and higher molecular weight (HMW) forms of Acrp30 depends upon formation of Cys22-mediated disulfide bonds because their reduction with dithiothreitol or substitution of Cys22 with alanine led exclusively to trimers. HMW and hexamer isoforms of Acrp30 activated NF-kappaB in C2C12 cells, but trimers, either natural, formed by reduction of Acrp30 hexamer, or formed by the C22A mutant, did not. In contrast, incubation of isolated rat extensor digitorum longus with naturally formed Acrp30 trimers or trimeric C22A Acrp30 led to increased phosphorylation of AMP-activated protein kinase-alpha at Thr172 and its activation. Hexameric and HMW Acrp30 could not activate AMP-activated protein kinase. Thus, trimeric and HMW/hexameric Acrp30 activate different signal transduction pathways, and Acrp30 represents a novel example of the control of ligand signaling via changes in its oligomerization state.
- Published
- 2003
- Full Text
- View/download PDF
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