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Activité de stimulation des défenses naturelles induites par des extraits de marc de raisin / Plant defense reactions induced by grape marc extractsBenouaret, Razik 13 February 2015 (has links)
Dans un contexte de réduction des intrants chimiques, l’utilisation des phytosanitaires naturels stimulant l’immunité végétale ouvre la porte vers une nouvelle approche de protection des plantes. Ces composés éliciteurs regroupés sous le terme de «Stimulateurs des Défenses naturelles des Plantes» (SDP) activent le système défensif de la plante la rendant plus résistante aux bio-agresseurs. Les SDP, de nature diverse, se présentent sous forme de composés uniques ou en mélange dans les extraits végétaux. Au cours de ma thèse, nous avons démontré l’activité SDP des extraits de marc de raisin. Les extraits issus de sous-produits de la vigne, marc de raisin rouge, marc de raisin blanc et pépins de raisin induisent diverses réactions de défense au sein de plantes modèles. Nous avons focalisé notre étude sur l’extrait de marc de raisin rouge (EMR) stimulant l’immunité chez le tabac. Infiltré sur feuilles, l’EMR induit la réponse de type HR caractérisée par l’apparition de lésions chlorotiques et accumulation de composés autofluorescents dans les tissus infiltrés. Ces réactions de défense locales ont été observées également chez l’arabette et la tomate. L’EMR déclenche les réponses LAR et SAR avec l’accumulation des transcrits des gènes de défense dans les feuilles de tabac et ce quelque soit son mode d’application (infiltration ou pulvérisation). Le mode d’action de l’EMR a été abordé sur cultures cellulaires de tabac BY-2. L’EMR induit une forte alcalinisation du milieu extracellulaire avec une mobilisation du calcium (Ca2+), l’expression des gènes de défense et la mort cellulaire. Une étude pharmacologique de la mort cellulaire suggère la mise en place de mort cellulaire programmée (PCD) dans les cellules de tabac. La caractérisation de la voie de signalisation activée par l’EMR a été étudiée avec le mutant NahG de tabac incapable d’accumuler l’acide salicylique (SA). Les réponses de défense (HR, LAR et SAR) sont faiblement induites par l’EMR chez le mutant nahG. L’EMR provoque une réponse de type HR fortement réduite avec une faible accumulation des composés autofluorescents et une diminution drastique de l’accumulation des transcrits des gènes PR suggérant l’intervention du SA dans l’induction des réactions de défense. Le degré de protection induit par l’EMR a été déterminé sur le pathosystème tabac/Phytophthora parasitica. Pulvérisé sur feuilles, l’EMR réduit de 45% les zones infectées par l’oomycète. Ce degré de protection semble être le résultat de l’activité antimicrobienne de l’EMR combinée à l’activité SDP. Aucune protection n’a été observée chez le mutant nahG confirmant l’implication de SA dans la résistance induite par l’EMR. Le fractionnement de l’EMR a permis de simplifier la formule active des extraits de raisin et d’identifier un mélange de molécules potentiellement capables d’induire l’activité SDP. Les composés actifs sont de nature polyphénolique et contiennent de la procyanidine B2 capable à elle seule d’induire la réponse de type HR et l’expression de l’antimicrobien PR1. Cependant, il semble que cette molécule agisse en association avec d’autres composés polyphénoliques pour stimuler le système défensif de la plante. / In order to reduce chemical inputs, the use of natural phytosanitary products stimulating plant immunity are emerging approaches in phytoprotection. These elicitor compounds known as "Plant Defense Inducers" (PDI) activate the plant defense system and improve their resistance to pests attack. PDI are single molecule or mixture of compounds extracted from plant. In my thesis, we demonstrated the PDI activity of different grape marc extracts. The winery byproducts, red grape marc extract, white grape marc extract and grape seed extract all induced various defense reactions in several plant models. We focused our study on the red grape marc extract (GME) which stimulates the immunity system in tobacco plants. When infiltrated into tobacco leaves, GME induced HR-like response characterized by the appearance of chlorotic lesions and accumulation of autofluorescent compounds in infiltrated tissues. Similar local defense reactions have been observed in Arabidopsis thaliana and tomato. GME also triggered LAR and SAR responses and induced defense gene transcript accumulation in tobacco leaves after infiltration or spraying. The GME mode of action was studied using the suspension-cultured cells of tobacco BY-2. GME induced rapid alkalinization of extracellular medium with calcium mobilization, expression of defense genes and cell death. A pharmacological approach of this defensive phenomenon suggests the establishment of programmed cell death (PCD) in tobacco cells. The characterization of the signaling pathway activated by GME was studied using tobacco nahG mutant unable to accumulate salicylic acid (SA). Defense responses (HR, LAR and SAR) induced by GME were impaired in the nahG mutant. GME drastically reduced HR-like response symptoms and PR transcript accumulation. These data suggest the implication of SA in the GME-induced plant defense reactions. The GME-induced protection was evaluated in the model pathosystem of compatible interaction between Nicotiana tabacum and Phytophthora parasitica var. nicotianae (Ppn). GME could reduce by 45% the infected areas induced by the oomycete on tobacco leaves. This level of protection was the result of the combined antimicrobial and PDI actions of GME. GME had no protecting effect against Ppn on NahG leaves evidencing the involvement of SA in the GME-induced resistance. GME fractionation led to identification of a bioactive molecule mixture capable of inducing the PDI activity. The active compounds are polyphenolics and involve procyanidin B2 which is by itself able to induce the HR-like response and PR1 transcript accumulation. This compound should act in combination with other polyphenolic molecules to stimulate the full plant defense reactions.
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A congruência de valores pessoais com o PDI em uma universidade federal: estudo com ênfase na inovação e sustentabilidade / A matching of personal values with the PDI in a federal university: study with emphasis on innovation and sustainabilityLucca, Carmem 20 December 2013 (has links)
Higher education has a significant contribution to scientific and technological development of a nation, through the training of professionals who work in the knowledge society. The Institutional Development Plan (IDP) can be considered as an instrument of management of universities, it allows the self knowledge, outlining goals, objectives and strategies, giving a direction to universities, avoiding lost opportunities. The scope of the study was to assessment the values shared by the managers and the strategic thinking of an institution of higher education. Data were collected through structured interviews with the governing body of the institution and document analysis, which are organized through a case study in the context of a descriptive exploratory study using mixed methodological approach (quantitative and qualitative). It was possible to draw up a profile of managers, identify the values and their relation to the process of innovation and sustainability, as well as some concepts related to the IDP of the research institution. The results showed a significant influence of the values of the managers in the adoption of sustainability with high levels for the value universalism and about innovation data showed less significant values. Research has shown that the university falls within the legal requirements because it presents innovative and sustainable strategies in the IDP. The evidences point that the institution makes efforts to enable their projects based on assumptions of an education focused on sustainability and innovation, which will be discussed, improved, planned and implemented more effectively grounded in clear and objective policies. The study leads to reflections on future educational and administrative decisions of the university, seeking innovative initiatives for the use and implementation of the IDP. / A educação superior tem contribuição significativa no desenvolvimento tecnológico e científico de uma nação, por meio da formação de profissionais que atuam na sociedade do conhecimento. O Plano de Desenvolvimento Institucional (PDI) pode ser considerado como um instrumento de gestão das universidades, pois possibilita o autoconhecimento, o delineamento de metas, objetivos e estratégias, dando um rumo às universidades, evitando a perda de oportunidades. O estudo teve como escopo a avaliação da convergência de valores dos gestores e o pensamento estratégico de uma instituição de educação superior. Os dados foram obtidos por meio de entrevistas estruturadas com o corpo diretivo da instituição e análise documental, sendo estes organizados por meio de estudo de caso em um contexto de pesquisa exploratória descritiva, utilizando abordagem metodológica mista (quantitativa e qualitativa). Foi possível elaborar o perfil dos gestores, identificar os valores e sua relação com o processo de inovação e sustentabilidade, bem como algumas concepções relativas ao PDI da instituição pesquisada. Os resultados apontaram influência significativa dos valores de gestores à adoção da sustentabilidade com índices elevados para o valor universalismo e com relação à inovação os dados assinalaram valores menos expressivos. A pesquisa mostrou que a universidade se insere nas exigências legais, pois apresenta estratégias sustentáveis e inovadoras em seu PDI. As evidências apontam que há esforços da instituição para viabilizar seus projetos com base em pressupostos de uma educação voltada para a sustentabilidade e inovação, os quais poderão ser discutidos, aprimorados, planejados e implementados de maneira mais efetiva alicerçados em políticas claras e objetivas. O estudo leva a reflexões sobre as futuras decisões pedagógicas e administrativas da universidade buscando iniciativas inovadoras para utilização e implementação do PDI.
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Studies on Redox-proteins and Cytokines in inflammation and CancerHossain, Akter January 2007 (has links)
The redox state in the cell plays a major role in determining vital functions and its major imbalance can lead to severe cell injury or death. Redox active proteins and cytokines involved in this process includes thioredoxin (Trx), protein disulfide isomerase (PDI), and tumor necrosis factor (TNF) superfamilies. Trx is a multipotent protein and key regulator of cellular redox balance operating in synergy with Trx reductase and NADPH (the Trx system). Trx has gene regulatory activity of several transcription factors. It also controls in a fascinating way redox-sensitive “on-off” decisions for apoptotic or hypertrophic pathways. Trx protects against H2O2 and TNFmediated cytotoxicity, a pathway in which TNF receptor-binding generates ROS. TNF is an autocrine growth factor and survival factor in vitro and in vivo for B-type of chronic lymphocytic leukemia (B-CLL) cells. The overall aim of this study was to investigate the importance of redox active proteins and cytokines in inflammation and cancer. We focused on: i) the role of Trx, TrxR, and selenium in carcinogenesis and in resistant cancer cells. ii) the importance of Trx in cancer cells and the redox regulation of TNF and its receptors TNFR1 and TNFR2. iii) the potential role of Trx as a key regulator in cellular redox balance, in the pathogenesis of cardiac dysfunction; its relationship to stress response parameters. iv) whether unmutated CLL (UCLL) responses to PKC and ROS pathways were different from mutated CLL (M-CLL) responses. Our results demonstrate pronounced selective selenium-mediated apoptosis in therapy resistant cells and suggest that redox regulation through the Trx system is an important target for cancer therapy. Trx was strikingly elevated in heart failure cases compared with controls signifying an adaptive stress response that is higher the more severe the disease. TNF autocrine release was redox modulated and the TNF receptors interacted at the cell surface membrane with the redox-active PDI, which excerted a stringent redox-control of the TNFR signaling. The proliferative response as well as increase of autocrine TNF and Trx were higher in U-CLL than in M-CLL. The overall conclusion of the four papers included in this thesis is that redox-active proteins and cytokines plays an important role in control and regulation of cancer and inflammation. Furthermore, redox regulation via thioredoxin by selenium, may offer novel treatment possibilities for resistant tumors disease.
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Development of PDI plates for Industrial ApplicationsSiddiqui, Muhammad Saad, Iqbal, Tahseen January 2010 (has links)
The aim of this Master’s Degree thesis project is to design and develop point diffraction interferometer plates. In this project the PDI plates are re-designed, changing the design which was used in previous projects in Halmstad University. The transparency of PDI plates can be controlled by coating them with NiCr film. Firstly, four plates with coating of different thickness of NiCr were developed. The relationship between transmittance and the thickness of NiCr was established by testing these plates for transmittance and reflectance with the help of a laser and an optical power meter. The absorption coefficient of clear substrates and reflection of light is also taken into account to achieve the correct results. The parameters like the diameter of semi-transparent area around the pinholes and the size of pinholes is chosen after fully understanding its application. The lay-out and description of design is also included in the report.
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Kristallographische Analyse von pathologischen Kristallen, Periplasmischen dömane von ligandfreien CitA Sensor Kinasen und PDI-verwandten Chaperone / Crystallographic Analysis of Pathological Crystals, Periplasmic Domain of Ligand-free CitA Sensor Kinase and PDI-related ChaperonesSevvana, Madhumati 04 July 2006 (has links)
No description available.
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Modeling Optical Properties of Combustion Soot emitted in the Troposphere / Modélisation de la réponse optique des particules de suie émises dans la TroposphèreGarcia Fernandez, Carlos 26 November 2015 (has links)
Ce travail concerne la modélisation, à l’échelle moléculaire, de l’interaction entre des nanoparticules carbonées et le rayonnement électromagnétique. Le but est d’aider à la compréhension des propriétés optiques des particules de suie afin de mieux quantifier l’influence des suies sur l’atmosphère et le climat. L’étude de l’interaction rayonnement/particules de suie fraîche a été effectuée par la méthode PDI ; il a été montré que : i) le coefficient d’absorption massique (MAC) des particules de suie dépend de la répartition des atomes dans la particule et de leurs liaisons, en particulier entre 200 et 350 nm ; ii) le MAC diffère selon que le cœur de la particule carbonée est occupé ou non par des plans graphitiques ; iii) un modèle analytique n’est pas adapté pour calculer le MAC d’une nanoparticule carbonée présentant des défauts structuraux. De plus, des méthodes de chimie quantique ont été utilisées pour caractériser le vieillissement des suies. Les résultats montrent que : i) NO, Cl, et HCl sont physisorbées sur une surface carbonée parfaite alors que sur une surface défective, ces espèces sont chimisorbées et conduisent à une modification de la surface ; ii) la présence de Cl conduit à un piégeage fort des molécules d’eau supérieur à celui obtenu lorsqu’un site oxygéné est présent sur la surface carbonée, expliquant ainsi le caractère hydrophile des suies émises lors d’incendies dans des milieux industriels. Enfin, la méthode PDI a été appliquée au calcul de la polarisabilité de HAP afin d’interpréter des spectres d’absorption des grains carbonés du milieu interstellaire, en incluant des molécules pour lesquelles aucune donnée n’était actuellement disponible. / This work concerns the modeling, at the molecular level, of the interaction between carbonaceous particles of nanometric size and the electromagnetic radiation. The goal is to improve our understanding of the optical properties of soot particles, to better quantify the influence of soot on the atmosphere and on climate change. The study of the interaction between radiation and fresh soot particles was carried out using the point dipole interaction method; it has been shown that: i) the mass absorption coefficient (MAC) of these soot nanoparticles may significantly depend on their atomistic details, especially between 200 and 350 nm; ii) the MAC depends on whether the heart of the carbonaceous particle is occupied or not by graphite planes; iii) an analytical model is not suitable for calculating the MAC of carbonaceous nanoparticles having structural defects. In addition, quantum chemical methods have been used to characterize the ageing of soot. The results obtained are i) NO, Cl, and HCl are physisorbed on a perfect carbonaceous surface whereas on a defective surface, these species are chemisorbed and lead to a modification of the surface; ii) on a carbonaceous surface, the presence of adsorbed Cl atoms leads to a strong trapping of the surrounding water molecules. This may be related to the highly hydrophilic nature of soot emitted during fires in industrial environments. Finally, the PDI method was applied to calculate the polarizability of PAHs to help at interpreting the absorption spectra of carbonaceous grains in the interstellar medium, including molecules for which no data was currently available.
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A DIGNIDADE HUMANA E A LIBERDADE ECONÔMICA: AS EXTERNALIDADES DA INDÚSTRIA FARMACÊUTICA E AS POLÍTICAS PÚBLICAS.Rodrigues, Edison Miguel 16 December 2015 (has links)
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EDISON MIGUEL RODRIGUES.pdf: 2154782 bytes, checksum: 638bda53df73b73ff0df1db7236c596e (MD5)
Previous issue date: 2015-12-16 / The Dissertation is part of the research area "Socio-Economic Relations" in their
"ethical and legal aspects" of the Postgraduate Program in Law, International Relations
and Development at the Catholic University of Goiás and from the human dignity
perspective, analyzes the externalities - social cost of the pharmaceutical industrial
activity in it´s exercise of economic freedom.
It starts with the assumption that the history of ideas through its different stages
culminated in the emptying of transcendent values, leaving just the market related
ones. The lack of values, coupled with the economic and demographic scenario,
causes externalities such as increasing the price of drugs, reducing the quality of
products and the precariousness of meeting the needs of the elderly population. It is
premised, however, that industrial activity is necessary to ensure innovation and
development of new medicines, which justifies state interference in the market, to
ensure the public interest. State intervention in the market would be guided by human
dignity as the foundation of the Democratic State of Brazil. It happens that, as a
concept under construction, human dignity lacks objectivity. Based on this, Barroso
proposes the following elements of human dignity: the intrinsic value of individual,
autonomy and community value. From this, explores some externalities relative to the
price and quality of drugs in the world, in Brazil and in regional perspective (State of
Goiás) caused by pharmaceutical corporate decisions taken on the full enjoyment of
economic freedom. It is concluded that to address externalities and the needs of the
elderly population without compromising own industrial activity (unintended
consequence) the state should intervene in the market through public policies,
especially in the Research, Development and Innovation (R&D). The methodology
used to demonstrate this was the literature on the subject and its correlation with the
data collected on price and quality of drugs. It uses the deductive-comparative
methodology based on historical and ethical analysis to analyze the data collected.
Cases or examples chosen for analysis were taken from the media in general, official
publications, academic papers, internet and others, and serve the purpose of exposing
the required state intervention in the market on behalf of human dignity, especially in
Research, Development and Innovation (R&D). / A Dissertação insere-se na linha de pesquisa Relações Socioeconômicas em seus
aspectos éticos e jurídicos , do Programa de Pós-Graduação em Direito, Relações
Internacionais e Desenvolvimento da Pontifícia Universidade Católica de Goiás e
analisa, a partir da dignidade humana, as externalidades - custo social - da atividade
industrial farmacêutica no exercício de sua liberdade econômica. Parte-se da hipótese
de que a história das ideias por meio dos seus diferentes momentos culminou no
esvaziamento de valores transcendentes, restando os mercadológicos. O
esvaziamento de valores, aliado ao cenário econômico e demográfico, provoca
externalidades como o aumento do preço dos medicamentos, a redução da qualidade
dos produtos e a precariedade do atendimento das necessidades da população idosa.
Tem como premissa, porém, que a atividade industrial é necessária para garantir a
inovação e desenvolvimento de medicamentos novos, o que justifica a interferência
do Estado no mercado para garantir o interesse público. A intervenção do Estado no
mercado seria pautada pela dignidade humana enquanto fundamento do Estado
Democrático de Direito Brasileiro. Ocorre que, como um conceito em construção, a
dignidade humana carece de objetivação. Barroso propõe que seriam elementos da
dignidade humana: o valor intrínseco do indivíduo, sua autonomia e o valor
comunitário. A partir disso, exploram-se algumas externalidades em relação ao preço
e qualidade dos medicamentos na perspectiva mundial, brasileira e regional (Estado
de Goiás) causadas por tomadas de decisões corporativas farmacêuticas no exercício
pleno da liberdade econômica. Conclui-se que para endereçar as externalidades e as
necessidades da população idosa, sem comprometer a própria atividade industrial
(consequência indesejada) o Estado deve interferir no mercado por meio de Políticas
Públicas, principalmente na área de Pesquisa, Desenvolvimento e Inovação (PDI). A
metodologia utilizada para demonstrar isso foi a pesquisa bibliográfica acerca do tema
e sua correlação com os dados levantados sobre preço e qualidade dos
medicamentos. Utiliza-se a metodologia dedutiva-comparativa fundamentada em
análises históricas e éticas para analisar os dados levantados. Os casos ou exemplos
escolhidos para análise foram retirados da mídia em geral, de publicações oficiais, de
trabalhos acadêmicos, internet e outros, e servem ao propósito de expor a necessária
intervenção do Estado no mercado em nome da dignidade humana principalmente na
área de Pesquisa, Desenvolvimento e Inovação (PDI).
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Proposição de plataforma co-design para processamento de imagens de sensoriamento remoto /Cardim, Guilherme Pina. January 2019 (has links)
Orientador: Erivaldo Antonio da Silva / Resumo: O processamento digital de imagens (PDI) consiste em uma área de grande interesse científico. Em Cartografia, o PDI é muito utilizado para extração de feições cartográficas de interesse presentes nas imagens de sensoriamento remoto (SR). Dentre as feições cartográficas, a detecção de malhas viárias é de grande interesse científico, pois proporciona a obtenção de informações atualizadas e acuradas para a realização de planejamentos urbanos. Devido à sua importância, a literatura científica possui diversos trabalhos propondo diferentes metodologias de extração de malhas viárias em imagens digitais. Dentre as metodologias, é possível encontrar metodologias propostas baseadas em lógica fuzzy, em detector de bordas e crescimento de regiões, por exemplo. Contudo, os estudos existentes focam na aplicação da metodologia de extração para determinadas áreas ou situações e utilizam recortes da imagem em seus estudos devido à grande quantidade de informações contidas nessas imagens. O avanço tecnológico proporcionou que imagens de SR sejam adquiridas com alta resolução espacial, espectral e temporal. Esse fato produz uma grande quantidade de dados a serem processados durante estudos desenvolvidos nessas imagens, o que acarreta um alto custo computacional e, consequentemente, um alto tempo de processamento. Na tentativa de reduzir o tempo de execução das metodologias de extração, os desenvolvedores dedicam esforços na redução da complexidade dos algoritmos e na utilização de outros recurs... (Resumo completo, clicar acesso eletrônico abaixo) / Resumen: El procesamiento digital de imágenes (PDI) consiste en un área de gran interés científico en diferentes áreas. En Cartografía, el PDI es muy utilizado en estudios de teledetección para extracción de los objetos cartográficos de interés presentes en las imágenes orbitales. Entre los objetos cartográficos de interés, la detección de redes viales se ha vuelto de gran interés científico proporcionando la obtención de informaciones actualizadas y precisas para la realización de planificaciones urbanas, por ejemplo. En este sentido, la literatura científica posee diversos trabajos proponiendo diferentes metodologías de extracción de redes viales en imágenes orbitales. Es posible encontrar metodologías propuestas basadas en lógica fuzzy, detector de bordes y crecimiento por región, por ejemplo. Sin embargo, los estudios existentes se centran en la aplicación de la metodología de extracción para determinadas áreas o situaciones y utilizan recortes de la imagen orbitales en sus estudios debido a la gran cantidad de informaciones contenidas en esas imágenes. Además, el avance tecnológico proporcionó que las imágenes de teledetección se adquieran con altas resoluciones espacial, espectral y temporal. Este hecho produce una gran cantidad de datos a ser procesados durante estudios desarrollados en esas imágenes, lo que acarrea en un alto costo computacional y, consecuentemente, un alto tiempo de procesamiento. En el intento de reducir el tiempo de respuesta de las metodologías de extracci... (Resumen completo clicar acceso eletrônico abajo) / Abstract: Digital image processing (DIP) consists of an area of great scientific interest in different areas. In Cartography, the DIP is widely used in remote sensing studies to extract cartographic features of interest present in orbital images. Among the cartographic features, the detection of road networks has become of great scientific interest, since it can provide accurate and updated information for urban planning, for example. In this sense, the scientific literature has several works proposing different methodologies of extraction of road networks in orbital images. It is possible to find proposed methodologies based on fuzzy logic, edge detector and growth by region, for example. However, the existing studies focus on the application of the extraction methodology to certain areas or situations and use orbital image cuts in their studies due to the large amount of information contained in these images. In addition, the technological advance has allowed the acquisition of remote sensing images with high spatial, spectral and temporal resolutions. This fact produces a large amount of data to be processed during studies developed in these images, which results in a high computational cost and, consequently, a high processing time. In an attempt to reduce the response time of the extraction methodologies, the developers dedicate efforts in reducing the complexity of the algorithms and in using some available hardware resources suggesting solutions that include software and hardwar... (Complete abstract click electronic access below) / Doutor
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Diabetes and Endoplasmic Reticulum Stress in Pancreatic beta-cells: Effects on Insulin Biosynthesis and beta-cell ApoptosisLai, Elida Wing Shan 30 July 2008 (has links)
Chronic hyperlipidemia (lipotoxicity) and hyperglycemia (glucotoxicity) have recently been shown to induce Endoplasmic Reticulum (ER) stress, which may contribute to pancreatic beta-cell dysfunction in type 2 diabetes. This thesis examined the involvement of ER stress in beta-cell lipotoxicity and glucotoxicity. Although chronic treatment with saturated free fatty acids (FFA) in vitro induced ER stress, altering ER stress by increasing or knocking-down GRP78 chaperone expression had no effect on apoptosis induction. Conversely, overexpression of ER chaperones rescued the reduction in proinsulin protein levels caused by chronic exposure to high glucose, although it had no effect on the decreased insulin mRNA levels and proinsulin translation rate. Thus, ER stress is likely not the main mechanism involved in saturated FFA-induced beta-cell apoptosis in vitro, but it may contribute to glucotoxic effects on proinsulin levels. These findings have increased our understanding of the link between ER stress and beta-cell dysfunction in type 2 diabetes.
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Diabetes and Endoplasmic Reticulum Stress in Pancreatic beta-cells: Effects on Insulin Biosynthesis and beta-cell ApoptosisLai, Elida Wing Shan 30 July 2008 (has links)
Chronic hyperlipidemia (lipotoxicity) and hyperglycemia (glucotoxicity) have recently been shown to induce Endoplasmic Reticulum (ER) stress, which may contribute to pancreatic beta-cell dysfunction in type 2 diabetes. This thesis examined the involvement of ER stress in beta-cell lipotoxicity and glucotoxicity. Although chronic treatment with saturated free fatty acids (FFA) in vitro induced ER stress, altering ER stress by increasing or knocking-down GRP78 chaperone expression had no effect on apoptosis induction. Conversely, overexpression of ER chaperones rescued the reduction in proinsulin protein levels caused by chronic exposure to high glucose, although it had no effect on the decreased insulin mRNA levels and proinsulin translation rate. Thus, ER stress is likely not the main mechanism involved in saturated FFA-induced beta-cell apoptosis in vitro, but it may contribute to glucotoxic effects on proinsulin levels. These findings have increased our understanding of the link between ER stress and beta-cell dysfunction in type 2 diabetes.
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