Effects of Prolonged Glucose Infusion on Insulin Signal Transduction and Glucose Transport in Rat Skeletal Muscle

Der Effekt einer in vivo Glucoseinfusion auf die Insulinwirkung im Skelettmuskel der Ratte wurde untersucht. Dazu wurden Dauerkatheter in die rechte Jugularvene implantiert und bis zum rechten Vorhof vorgeschoben. Anschließend wurden die Katheter mit einem Perfusor verbunden. Nach einer zweitägigen Erholungsphase vom Operationsstress, wurde 50%ige Glucose mit einer Infusionsrate von 2 ml/h für zwei oder fünf Tage durchgeführt. Die Kontrolltiere erhielten eine 0,45% Kochsalzinfusion für dieselbe Infusionsdauer. Anschließend wurden die Ratten geopfert und Skelettmuskel vom Schenkel entnommen. Im Westernblott wurde eine signifikante Erhöhung der GLUT4-Protein-expression nach zwei Tagen und nach fünf Tagen beobachtet. Die GLUT1 Proteinexpression war über die gesamte Infusionsperiode nicht verändert. Eine Translokation zu der Plasmamembran wurde gezeigt und kann wahrscheinlich die Normalisierung der Blutzuckerwerte in den mit Glukose infundierten Tieren nach fünf Tagen erklären. Unsere Untersuchungen zeigen, daß Hyperglykämie zu einer Verringerung der Proteinexpression und Tyrosinphosphorylierung des Insulinrezeptors am fünften Tag der Infusion geführt hat. Die Proteinexpression des IRS-1 und PI3-K waren für die Gesamtinfusionszeit unverändert. Weiterhin konnten wir zeigen, daß die Proteinexpression und die Translokation einiger PKC-Isoformen verändert waren, wobei die Translokation der PKC-Isoformen PKCbI und PKCbII und in einem geringeren Maße der PKCa am stärksten waren. Die Proteinexpression der Glucosamine:Fructose-6-Phosphat Amidotransferase war stark erhöht. Weiterhin haben wir gezeigt, daß die Protein Kinase B-Phosphorylierung nicht verändert war. Unsere Ergebnisse zeigen, daß Hyperglykämie zu einer Glukoseaufnahme in den Muskel in einem Insulin-unabhängigen Weg führen kann.Glucose toxicity represents a well-established term referring to hyperglycemia as a potent contributor to the impairment of insulin action on insulin sensitive tissue. We set up an animal model to investigate the in vivo effects of glucose infusion on insulin signaling. Chronic catheter were implanted via right jugular vein into right atrium, routed subcutaneously and externalized between the shoulders to be connected to a Perfusor syringe pump. After a recovery period of 48 h, glucose (50%) was continuously infused at a rate of 2.0 ml/h over a period of 48 h or extended to 120 h, whereas control animals received 0.45% saline. Animals were scarified and mixed hind limb muscles were subsequently excised. Western blotting analysis revealed a significant increase in protein expression of GLUT4 after 48 h and after 120 h of glucose infusion. GLUT1 was unaffected during the whole period of infusion. Hyperglycemia induced changes at the level of insulin receptor showing a significant decrease in protein expression and tyrosine phosphorylation of insulin receptor after 120 h of glucose infusion. IRS-1 and PI3-kinase were unaffected during the whole infusion period, whereas marked change was observed in PKC isoforms expression and translocation. Among the latter, PKCbI and PKCbII and to a less extent PKCa were mostly translocated. The glucosamine:fructose-6-phosphate amidotransferase (GFAT) expression was highly activated (3 fold at protein and 7 fold at messenger level). Glucose infusion affected neither PKB expression the serine phosphorylation of the latter. Glucose transporter translocation to the plasma membrane was shown and might explain normoglycemia seen in treated animals at the end of the glucose infusion period. Our results suggest that hyperglycemia per se might propagate its uptake into skeletal muscle in an insulin-independent manner involving PKC translocation and GFAT activation

Role of PKCΖ translocation in the development of type 2 diabetes in rats following continuous glucose infusion

Aim We investigated the molecular mechanisms of hyperglycaemia-induced insulin resistance and type 2 diabetes in rats receiving a continuous glucose infusion (GI). Methods Female Wistar rats were infused with either 2.8 mol/L glucose or saline (2 mL/h) for durations varying from 0 to 15 days. Blood samples were analysed daily to determine glucose and insulin dynamics. Subsets of animals were sacrificed and solues muscles were extracted for determination of protein expression, subcellular location, and activities of insulin-signalling proteins. Results Rats accommodated this systemic glucose oversupply and developed insulin resistance on day 5 (normoglycaemia/hyperinsulinaemia) and type 2 diabetes on day 15 (hyperglycaemia/normoinsulinaemia). The effect of GI on protein kinase CΖ (PKCΖ) activity was independent of changes in phosphatidylinositol 3-kinase activity, and occurred in parallel with an increase in PDK1 activity. Activated PKCΖ was mainly located in the cytosol after 5 days of GI that was coincident with the translocation of GLUT4 to the plasma membrane, and normoglycaemia. After 15 days of GI, PKCΖ translocated from the cytosol to the plasma membrane with a concomitant decrease in PDK1 activity. This caused an increase in the association between PKCΖ and PKB and a decrease in PDK1–PKB reactions at the plasma membrane, leading to reduced PKB activity. The activity of PKCΖ per se was also compromised. The PKCΖ and PKB activity reduction and the blunted insulin-stimulated GLUT4 translocation eventually led to hyperglycaemia and diabetes. Conclusion Translocation of PKCΖ may play a central role in the development of type 2 diabetes. Copyright © 2009 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64921/1/1056_ftp.pd

Desarrollo de una herramienta capaz de generar planes de marketing

La dotación de una herramienta que sea capaz de generar un plan de marketing y plasmarlo sobre papel a una empresa y facilitar al usuario el desarrollo del mismo de manera secuencial con el fin de optimizar, y agilizar los procesos de una forma óptima, competitiva y fiable La realización de este proyecto final de carrera es fruto a la gran necesidad de las empresas de implantación de sistemas de información capaces de generar planes de marketing, ya que este va a ser un factor decisivo en su éxito, rentabilizar las necesidades de una empresa de comercialice tanto productos como servicios. El programa se ha basado en el análisis de los requerimientos de una empresa y en lo que las grandes empresas creen importante. La interfaz de la aplicación se ha desarrollado de manera que tenga un diseño simple, intuitivo y secuencial en su uso y capaz de llamar la atención del usuario para su mayor rendimiento.Houdali, N. (2007). Desarrollo de una herramienta capaz de generar planes de marketing. Universitat Politècnica de València. http://hdl.handle.net/10251/50047Archivo delegad

Purchase intention in relation to delivery in grocery stores in millennials of Lima

La presente investigación presenta un análisis destacado de las acciones de retención en bodegas relacionadas con la intención de compra. En las bodegas hacen uso de acciones para aumentar la intención de compra pero los bodegueros no saben que están haciendo uso de ellas o no están bien informados, por ende no les queda claro cómo influyen en la compra. No se valoran mucho las estrategias de retención que podrían realizar las bodegas para influir de mayor manera en la compra. En el siguiente estudio se verán las acciones más importantes de las bodegas y qué relación tienen con la intención de compra. Este estudio sirve para que las bodegas pueda darse cuenta de que acciones son las más relevantes. La siguiente investigación será de tipo mixto, ya que empieza con la recolección de información de la realidad de los participantes, la cual permitirá afinar los instrumentos para la medición cuantitativa. En ese enfoque, se intenta encontrar regularidades y relaciones además de poder ver si se aprueba la hipótesis y por consiguiente explicar el fenómeno de las tiendas de conveniencia, ya que las variables se asocian: las estrategias de plaza y la calidad impactan en la preferencia de compra de los clientes. De manera que se podrá conocer de qué manera impactan una en la otra, lo cual identifica la correlación. Asimismo, es descriptivo, ya que se va a definir los datos empíricos que vamos a recoger. Con el propósito de responder a través de este trabajo las preguntas iniciales y herramientas cualitativas se obtiene conclusiones en base a los hallazgos. Dentro de los resultados cualitativos encontramos cuatro acciones muy importantes utilizadas por bodegas: La confianza del vendedor con sus clientes, el tiempo de entrega del delivery, el fiado, el contacto con los productos y el costo del delivery. Se encontró al igual que los resultados cuantitativos, que existe una relación con la intención de compra en cada una de las acciones. Se evidencio que la relación es débil y media.The present investigation presents an outstanding analysis of retention actions in warehouses related to the purchase intention. In the wineries they make use of actions to increase the intention of purchase but the winemakers do not know that they are making use of them or are not well informed, therefore it is not clear to them how they influence the purchase. The retention strategies that wineries could carry out to influence the purchase in a greater way are not valued much. In the following study you will see the most important actions of the wineries and how they relate to the purchase intention. This study serves to allow wineries to realize which actions are the most relevant. The following investigation will be of mixed type, since it begins with the collection of information on the reality of the participants, which will allow refining the instruments for quantitative measurement. In this approach, we try to find regularities and relationships in addition to being able to see if the hypothesis is approved and therefore explain the phenomenon of convenience stores, since the variables are associated: the strategies of place and quality impact on the preference of Customer purchase. So you can know how they impact one on the other, which identifies the correlation. It is also descriptive, since the empirical data that we are going to collect will be defined. With the purpose of answering through this work the initial questions and qualitative tools, conclusions are obtained based on the findings. Among the qualitative results we find four very important actions used by wineries: The trust of the seller with their customers, the delivery time of the delivery, the trust, the contact with the products and the cost of delivery. It was found, like the quantitative results, that there is a relationship with the intention to purchase in each of the shares. It was evident that the relationship is weak and medium.Trabajo de investigació

RF Infrastructure Cooperative System for in Lane Vehicle Localization

This paper presents a sensor which can be included in an Advanced Driver Assistance System (ADAS) that is compliant with the Vehicle to Infrastructure communication standard (V2I). This system allows estimation of the vehicle lateral position in real time by ensuring cooperation between an on-board vehicle system and passive transponders integrated in the lateral white strips of the road. Based on an optimization method, the lateral position vehicle is provided with a distance error less than 3 cm. In this paper, experimental results are presented in order to evaluate the robustness of the proposed system in a realistic environment. Three scenarios are considered to take into account the bitumen properties, the presence of parasitic reflectors in different positions around the system and the interaction between transponders

Time-domain PLL modeling and RJ/DJ jitter decomposition

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