Type 2 diabetes mellitus (T2DM) ensues from diminished insulin sensitivity and abated compensatory insulin secretion. While diminished insulin secretion has a strong genetic origin, environmental factors are central in the development of insulin resistance; these include hyperinsulinemia and lipotoxicity. Insulin resistance results in the dysregulation of hypothalamic neurons that mediate its central actions: a key intermediary neuron is the neuropeptide Y/agouti-related peptide (NPY/AgRP) neuron. The hypothesis therefore was generated that insulin directly regulates NPY/AgRP neurons, and that prolonged insulin or palmitate, a prevalent free fatty acid (FFA), exposure inhibits neuronal insulin signaling. Using well characterized hypothalamic cell lines, mHypoE-46 or mHypoE-44, which express NPY, AgRP and insulin receptor signaling machinery, this hypothesis was examined in three studies. Correspondingly, insulin decreased NPY and AgRP mRNA expression in the mHypoE-46 cells, through an extracellular signal-regulated kinase (ERK) dependent mechanism; whereas prolonged exposure of NPY/AgRP cells to insulin or palmitate attenuated insulin signaling, determined by analysis of phosphorylated Akt. Insulin induced insulin receptor substrate-1 (IRS-1) serine 1101 phosphorylation in mHypoE-46 cells, utilizing the mTOR-S6K1 pathway, as the mTOR inhibitor rapamycin prevented IRS-1 serine phosphorylation. Insulin also decreased insulin receptor and IRS-1 protein levels; this was prevented by lysosomal and proteasomal pathway inhibitors, 3-methyladenine and epoxomicin, respectively. Importantly, rapamycin, epoxomicin or 3-methyladenine pre-treatment decreased the attenuation of insulin signaling during long-term insulin exposure. On the other hand, palmitate activated c-Jun N-terminal kinase (JNK), the apoptosis effector caspase 3, and induced endoplasmic reticulum (ER) stress in mHypoE-44 cells: JNK inhibition prevented ER stress. In an attempt to avert the deleterious effects of palmitate, the neuronal cells were treated with the 5`AMP-activated protein kinase (AMPK) activator AICAR, a possible insulin sensitizer. Interestingly, AICAR attenuated JNK and caspase 3 activation, and restored insulin signaling. These findings demonstrate that insulin directly regulates NPY/AgRP neuronal cells, and that insulin and palmitate provoke neuronal insulin resistance through different mechanisms. These findings substantiate the idea that environmental factors known to trigger peripheral insulin resistance may have consequences at the level of the individual hypothalamic neuron, which may ultimately contribute to the resulting pathophysiological states of obesity and T2DM.

Type 2 diabetes mellitus (T2DM) ensues from diminished insulin sensitivity and abated compensatory insulin secretion. While diminished insulin secretion has a strong genetic origin, environmental factors are central in the development of insulin resistance; these include hyperinsulinemia and lipotoxicity. Insulin resistance results in the dysregulation of hypothalamic neurons that mediate its central actions: a key intermediary neuron is the neuropeptide Y/agouti-related peptide (NPY/AgRP) neuron. The hypothesis therefore was generated that insulin directly regulates NPY/AgRP neurons, and that prolonged insulin or palmitate, a prevalent free fatty acid (FFA), exposure inhibits neuronal insulin signaling. Using well characterized hypothalamic cell lines, mHypoE-46 or mHypoE-44, which express NPY, AgRP and insulin receptor signaling machinery, this hypothesis was examined in three studies. Correspondingly, insulin decreased NPY and AgRP mRNA expression in the mHypoE-46 cells, through an extracellular signal-regulated kinase (ERK) dependent mechanism; whereas prolonged exposure of NPY/AgRP cells to insulin or palmitate attenuated insulin signaling, determined by analysis of phosphorylated Akt. Insulin induced insulin receptor substrate-1 (IRS-1) serine 1101 phosphorylation in mHypoE-46 cells, utilizing the mTOR-S6K1 pathway, as the mTOR inhibitor rapamycin prevented IRS-1 serine phosphorylation. Insulin also decreased insulin receptor and IRS-1 protein levels; this was prevented by lysosomal and proteasomal pathway inhibitors, 3-methyladenine and epoxomicin, respectively. Importantly, rapamycin, epoxomicin or 3-methyladenine pre-treatment decreased the attenuation of insulin signaling during long-term insulin exposure. On the other hand, palmitate activated c-Jun N-terminal kinase (JNK), the apoptosis effector caspase 3, and induced endoplasmic reticulum (ER) stress in mHypoE-44 cells: JNK inhibition prevented ER stress. In an attempt to avert the deleterious effects of palmitate, the neuronal cells were treated with the 5`AMP-activated protein kinase (AMPK) activator AICAR, a possible insulin sensitizer. Interestingly, AICAR attenuated JNK and caspase 3 activation, and restored insulin signaling. These findings demonstrate that insulin directly regulates NPY/AgRP neuronal cells, and that insulin and palmitate provoke neuronal insulin resistance through different mechanisms. These findings substantiate the idea that environmental factors known to trigger peripheral insulin resistance may have consequences at the level of the individual hypothalamic neuron, which may ultimately contribute to the resulting pathophysiological states of obesity and T2DM.

Diss. (sammanfattning). Uppsala : Sveriges lantbruksuniv. / Härtill 4 uppsatser.

The objective of the study was to analyze the relationship of psychrotrophic lipolytic bacteria in bulk samples of cow?s raw milk and their metabolic activity based on the content of free fatty acids and identifying the factors that may influence their levels. The contents of free fatty acids (FFA) and counts of total bacteria, psychrotrophic lipolytic bacteria (PLiBC) and somatic cells were determined in 150 samples of cow?s bulk raw milk on 20 farms with three different milking technologies in South Bohemia during 2008?10. FFA were determined using an extraction-titration method. Within the compared technologies, the highest mean values of FFA (38,8 mmol?kg-1; P<0,001) and PLiBC (696 CFU?ml?1) were observed on farms with pipeline milking in stalls. The lowest mean FFA level (15,4 mmol?kg-1) was determined on farms with an automatic milking system. Medium values were determined on farms with parlour milking. From the aspect of the inhibition of an increase in psychrotrophic bacteria, and mainly in psychrotrophic lipolytic bacteria in conditions of cold storage of raw milk the temperature of 4°C seems optimum as it markedly inhibits the growth of mesophilic and psychrotrophic bacteria and at the same time the increase in the values of free fatty acids is slower at this temperature compared to the temperatures of 6,5 and 10°C.

Submitted by Clebson Anjos (clebson.leandro54@gmail.com) on 2016-03-04T20:35:17Z No. of bitstreams: 1 arquivototal.pdf: 1623954 bytes, checksum: 8a3abb877583d97539e60ac1388438ee (MD5) / Made available in DSpace on 2016-03-04T20:35:18Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1623954 bytes, checksum: 8a3abb877583d97539e60ac1388438ee (MD5) Previous issue date: 2015-02-02 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The study of proteolysis, lipolysis volatiles profile of caprine Coalho cheese to which were added probiotic bacteria during storage. The cheeses were named: QS, control sample of Coalho cheese prepared with a starter culture of Lactococcus lactis, subsp. lactis, and Lactococcus lactis, subsp. cremoris; QLA, Coalho cheese with culture of Lactobacillus acidophilus; QLP, Coalho cheese sample formulated with Lactobacillus paracasei; QB, Coalho cheese with Bifidobacterium lactis; and QC, Coalho cheese with co-culture containing the 3 microorganisms in associated. The cheeses were analyzed after 1, 7, 14, 21 and 28 days of storage at the temperature of 10 °C ± 2 °C. The probiotic cell counts in cheese was superior to 6.5 log CFU g⁻¹ of cheese in the first day of storage, and surpassed 7 log CFU g⁻¹ of cheese in the 28th day of storage. Based on comparative studies carried out, it must be highlighted that the use of the various probiotic lactic cultures affects the lipid, protein, and aromatic profiles of caprine Coalho cheese during storage. It was verified that, when they were added to the Coalho cheese samples, the lactic cultures, regardless of type, presented lipolytic action (p < 0.01) during storage, causing a reduction in long chain fatty acids and an increase in short chain fatty acids. The acids released have direct influence in particular compounds of the aroma of the product, especially the characteristic caprine aroma, with an increase in caprylic, caproic and capric acids. It was observed that the addition of the Bifidobacterium lactis culture and the co-culture of probiotics had a positive effect on the fatty acid profile, with a higher production of volatiles, resulting in more concentrations during the CLA storage period (0.74 and 0.54 g/100 g of fatty acids), optimal values for the PUFA/SFA relationships (0.23 and 0.065) and DFA (50.23 and 45.08), associated with a reduction in the atherogenicity index (2.15 and 2.38) and in the trombosidade index (1.69 and 1.82). Twenty-five volatile compounds were identified in caprine Coalho cheese: six alcohols, four hydrocarbons, four terpenes, three acids, three ketones, three aldehydes and two esters. In the five types of cheese samples analyzed, one was able to observe the production of esters during storage and the reduction of aldehydes. The fruity aroma of esters is desirable, since it lessens undesirable aromas which are found in some compounds such as acids and aldehydes. The use of a combination of probiotic cultures (co-culture) also influenced (p < 0,01) the proteolysis of caprine Coalho cheese, providing a higher percentage of soluble protein, a higher proteolytic depth index and a greater release of fatty acids in the first day after processing.The probiotic caprine Coalho cheese samples presented a proteolysis rate which was at its highest after seven days of storage, and their fractions of αs₂ and k-casein were the ones with the highest degree of hydrolysis during storage. Among the samples prepared using isolated probiotic bacteria, it must be emphasized that B. lactis presented a more intense proteolytic action, showing a high percentage of soluble protein and a greater degradation of the αs₂ casein during storage. Probiotic cheeses produced using goat milk have excellent characteristics in terms of nutritional and aromatic attributes; highlighted the B. lactis and prodizidos adding the co-culture of probiotics. / O estudo da proteólise, lipólise e perfil de voláteis de queijo de coalho caprino ao qual foram adicionadas bactérias probióticas durante o armazenamento. Os queijos foram denominados de: QS, queijo de coalho controle elaborado com a cultura “starter” de Lactococcus lactis subsp. lactis e Lactococcus lactis subsp. cremoris; QLA, queijo de coalho com cultura de Lactobacillus acidophilus; QLP, queijo de coalho elaborado com Lactobacillus paracasei; QB, queijo de coalho com Bifidobacterium lactis; e QC, queijo de coalho com co-cultura, contendo os 3 micro-organismos em associado. Os queijos foram analisados após 1, 7, 14, 21 e 28 dias de armazenamento a 10 °C ± 2 °C. A contagem das células probióticas nos queijos foi superior a 6,5 log UFC g-1 de queijo no 1° dia de armazenamento e 7 log UFC g-1 de queijo, no 28° dia. Com base nos estudos comparativos realizados, ressalta-se que o uso das diferentes culturas láticas probióticas afetou o perfil lipídico, proteico e aromático do queijo de coalho caprino, durante o armazenamento. Verificou-se que as culturas láticas, independente do tipo, quando adicionadas aos queijos de coalho, apresentaram ação lipolítica (p < 0,01) durante o armazenamento, provocando a redução dos ácidos graxos de cadeia longa e aumento dos ácidos graxos de cadeia curta. Os ácidos liberados influenciaram diretamente nos compostos do aroma peculiar do produto, principalmente, o aroma característico de caprinos, com aumento dos ácidos caprílico, caproico e cáprico. Observou-se efeito positivo da adição da cultura de Bifidobacterium lactis e da co-cultura de probióticos no perfil de ácidos graxos, e uma maior produção de voláteis, que resultou em maiores concentrações durante o período de estocagem do CLA (0,74 e 0,54 g/100g de ácidos graxos), e ótimos valores das relações AGPI/AGS (0,23 e 0,065) e DFA (50,23 e 45,08), associados à redução dos índices de aterogenicidade (2,15 e 2,38) e trombosidade (1,69 e 1,82). Vinte e cinco compostos voláteis foram identificados no queijo de coalho caprino: sendo seis alcoóis, quatro hidrocarbonetos, quatro terpenos, três ácidos, três cetonas, três aldeídos e dois ésteres. Nos cinco tipos de queijos de coalho caprino avaliados, observou-se produção de ésteres ao longo do armazenamento e redução de aldeídos. O aroma frutado dos ésteres é almejável, uma vez que suaviza aromas indesejáveis e característicos de alguns compostos como ácidos e aldeídos. A utilização da combinação das culturas probióticas (co-cultura) também influenciou (p < 7 0,01) a proteólise do queijo de coalho caprino, proporcionando maior teor de proteína solúvel, maior índice proteolítico de profundidade e maior liberação de aminoácidos no 1° dia após o processamento. Os queijos de coalho caprinos probióticos apresentaram índice de proteólise em extensão máxima após sete dias de estocagem, sendo que suas frações de αs2 e k-caseína foram as que obtiveram maior grau de hidrólise ao longo do armazenamento. Dentre os queijos elaborados com bactérias probióticas isoladas, enfatiza-se que a B. lactis exibiu ação proteolítica mais intensa, proporcionando elevado teor de proteína solúvel e maior degradação da fração de αs2 caseína ao longo do armazenamento. Os queijos probióticos fabricados a partir de leite de cabra possuem excelentes características em relação aos atributos nutricionais e aromáticos, em destaque os prodizidos adicionando Bifidobacterium lactis e a co-cultura de probióticos.

abstract: A mule deer herd exists on the northern rim of the Grand Canyon, located on the North Kaibab Plateau. Historical references to this indigenous mule deer herd presented reports of periodic population irruption and collapse. Partially funded by the Arizona Game and Fish Department and the Arizona Deer Association, examination of herd nutritional and metabolic status from the Fall 2005 - Spring 2008 was completed at the request of AzGFD and ADA. Habitat analysis included forage micro-histological, protein, and caloric content plus whole blood and plasma assays gauging herd metabolic response. Modelling was completed using best management practices wildlife energy demand calculations and principal component analysis. Forage quality analysis and modelling suggest a sufficient amount of nitrogen (N) available (DPI) to the deer for protein synthesis. Energy analysis (MEI) of forage suggest caloric deficiencies are widely prevalent on the north Kaibab plateau. Principal component analysis integrates forage and metabolic results providing a linear regression model describing the dynamics of forage utilization, energy availability, and forage nitrogen supply with metabolic demand and response of the mule deer herd. Most of the plasma and blood metabolic indicators suggest baseline values for the North Kaibab mule deer. Albumin values are in agreement with albumin values for mule deer in the Southwest. I suggest that the agreed values become a standard for mule deer in the Southwestern U.S. As excess dietary N is converted to a caloric resource, a continual state of under-nutrition exists for the deer upon entering the N. Kaibab winter range. The population is exceeding the nutritional resource plane that the winter habitat provides. Management recommendations include implementation of multiple small-scale habitat rehabilitation efforts over time, including invasive juniper (Juniperous osteosperma) and piñon (Pinus edulis) management, prescribed burning to control big sage (Artemesia tridentata) populations, and reseeding treated areas with a seed mix of native shrubs, grasses and forbs. I recommended that the population size of the North Kaibab deer herd is maintained at the current size with natural selection controlling growth, or the population be artificially reduced through increased hunting opportunities. / Dissertation/Thesis / Ph.D. Environmental Design and Planning 2014

Made available in DSpace on 2017-07-10T18:08:05Z (GMT). No. of bitstreams: 1 Thiago Olinek Reinehr.pdf: 1676955 bytes, checksum: 631870403f8cb9a7b67a1425774d480b (MD5) Previous issue date: 2015-11-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Enzymatic hydrolysis is an important industrial process used to alter oils and fats. Products obtained by this reaction are free fatty acids, monoacylglycerols, diacylglycerols and glycerol, which are used as raw materials for a wide variety of industrial applications. The main limitations of the enzymatic hydrolysis of oils and fats are the immiscibility of the reactants and the inhibition effect caused by increased substrate concentration. The use of ultrasound has emerged as a powerful resource in immiscible substrates processes. The objective of this study was to evaluate different application methods of ultrasonic irradiation on the enzymatic hydrolysis of soybean oil. Kinetics were performed using ultrasound bath, ultrasound probe, and pre-emulsion with and without ultrasound probe ultrasound. The effects of substrate inhibition, surfactant concentration (gum arabic), enzyme load and time preemulsion were also investigated. Mathematical simulations of the process were also performed. The substrate inhibition was evident from the mole fraction of 2.5 % oil in the reaction medium. The surfactant concentration that provided higher rates was 10 mathrmg L-¹. The enzyme loading showed a fraction of saturation at 2.0 % by mass, relative to the mass of water, only for the ultrasound-free reaction, indicating the increase in interfacial area where the substrates were exposed to ultrasound. Even the smallest pre-emulsion times were significant in the initial rate of hydrolysis. Kinetic experiments exposed to ultrasonic irradiation throughout the reaction period showed evidence of significant enzymatic deactivation. The methodology that uses pre-emulsion with probe ultrasound showed better results for the rate of reaction with no evidence of enzyme deactivation. Hydrolysis mathematical simulations were in agreement with the experimental evidence. / A hidrólise enzimática é um importante processo industrial para modificação de óleos e gorduras. Os produtos obtidos através dessa reação são ácidos graxos livres, monoacilgliceróis, diacilgliceróis e glicerol, que são usados como matériasprimas de uma grande variedade de aplicações industriais. As principais limitações da hidrólise enzimática de óleos e gorduras são a imiscibilidade dos reagentes e o efeito de inibição causado pelo aumento da concentração de substrato. O uso de ultrassom tem se apresentado como um recurso poderoso em processos de substratos imiscíveis. Este trabalho teve objetivo de avaliar diferentes metodologias de aplicação de irradiação ultrassônica na hidrólise enzimática do óleo de soja. Foram realizadas cinéticas utilizando ultrassom de banho, ultrassom de sonda, préemulsão com ultrassom de sonda e sem ultrassom. Também foram investigados os efeitos da inibição pelo substrato, concentração de surfactante (goma arábica), da carga enzimática e do tempo de pré-emulsão. Simulações matemáticas do processo também foram realizadas. A inibição pelo substrato foi evidente a partir da fração molar de 2,5% de óleo no meio reacional. A concentração de surfactante que forneceu maiores taxas foi de 10 g L-¹. A carga enzimática apresentou uma fração de saturação em 2,0% de massa em relação a massa de água, apenas para a reação livre de ultrassom, indicando o aumento de área interfacial quando os substratos foram expostos ao ultrassom. Até mesmo os menores tempos de pré-emulsão foram significativos na taxa inicial de hidrólise. Os experimentos cinéticos expostos a irradiação ultrassônica por todo período reacional apresentaram evidências de desativação enzimática expressiva. A metodologia que empregou pré-emulsão com ultrassom de sonda apresentou melhores resultados para a taxa de reação sem indícios de desativação enzimática. As simulações matemáticas da hidrólise foram concordantes com as evidências experimentais.

ABSTRACTThe prevalence of diabetes is increasing dramatically, incurring a major health and socioeconomic burden. Type 2 diabetes (T2D), the most prevalent form of diabetes, results from a variable combination of insulin resistance and insulin deficiency, secondary to pancreatic β-cell failure. These defects are caused by a complex interplay between genetic and environmental/ lifestyle factors. Among the latter, poor dietary quality is a crucial driver of T2D development. Although adopting healthy dietary habits is considered as a mainstay for T2D prevention, what constitutes a healthy diet remains controversial. Epidemiological studies examining the association of dietary fat quality with T2D incidence have yielded equivocal results and may suffer from confounding. On the other hand, randomized trials assessing the impact of dietary fat saturation on glucose homeostasis have major methodological shortcomings, precluding reliable conclusions. In order to elucidate this question, we compared the effects of palm oil vs olive oil on glucose homeostasis and other relevant metabolic parameters, in a mouse model of high-fat diet-induced obesity. The saturated fatty acid-rich palm oil is the most abundantly used oil worldwide. Olive oil is a staple food of the Mediterranean diet, rich in monounsaturated fatty acids and widely regarded as healthful. In this model, palm oil was not more harmful than olive oil with regard to glucose/insulin homeostasis. However, palm oil was associated with increased visceral adiposity and triglyceridemia compared to olive oil. Circulating and tissue free fatty acid (FFA) concentration and composition are determined by dietary factors, as well as genetic and metabolic factors. There is accumulating evidence indicating that increased FFA levels and/or an unbalanced FFA composition with excess palmitate, induce β-cell dysfunction and apoptosis (lipotoxicity). To characterize the mechanisms underlying lipotoxicity, we combined RNA-sequencing with proteomics of β-cells exposed to palmitate, the most prevalent SFA in humans. This cross-omics study showed that palmitate altered lipid and amino-acid metabolism, and affected amplifying pathways of insulin secretion and exocytosis. Furthermore, palmitate induced stress pathways, including mitochondrial dysfunction, oxidative stress and endoplasmic reticulum (ER) stress. ER stress is triggered when protein folding demand exceeds ER folding capacity. This response aims to restore ER homeostasis but if unresolved, it can become deleterious. Islets from T2D patients display signs of ER stress, pointing to a potentially pathogenic role of the latter.Monogenic and neonatal diabetes are rare forms of diabetes caused by single gene mutations. These forms are of particular interest, as they can serve as ‘human knockout’ models of diabetes. Recent evidence shows that there is overlap in the genetic basis of monogenic diabetes and T2D, suggesting that they may be part of a pathologic continuum. To explore the role of ER stress in diabetes pathogenesis, we studied two different genetic syndromes involving neonatal or early-onset diabetes, caused by mutations in genes related to ER function (DNAJC3 and YIPF5). Using in vitro knockdown models, we showed that ER stress elicited by impaired chaperone function (DNAJC3) or by impaired ER-to-Golgi protein transport (YIFP5) causes β-cell apoptosis. Altogether, our findings support that lipotoxic and genetic ER stress contribute to diabetes pathogenesis. Preventing or modulating ER stress thus holds anti-diabetic therapeutic potential. Future research should focus on defining optimal strategies to restore a balanced FFA profile and enhance ER function, aiming to prevent ER-stress induced β-cell failure. RésuméLa prévalence du diabète progresse constamment, posant un défi sanitaire et socioéconomique majeur. Le diabète de type 2 (DT2), la forme la plus courante de diabète, résulte de la résistance à l’insuline, en association avec un déficit insulinique dû à la défaillance des cellules β pancréatiques. Ces anomalies découlent d’une interaction complexe entre des facteurs génétiques et des facteurs liés au mode de vie. Parmi ces derniers, la qualité du régime alimentaire est un facteur crucial pour le développement du DT2. Bien que le suivi d’un régime alimentaire sain est considéré comme le pilier pour la prévention du DT2, ce qui constitue un régime sain demeure un sujet de controverse.Les études épidémiologiques examinant l’association entre la qualité de la graisse alimentaire et l’incidence du DT2 ont donné des résultats équivoques, affectés éventuellement par des facteurs confondants. En outre, les études randomisées évaluant l’impact du degré de saturation de la graisse alimentaire sur l’homéostasie du glucose comportent des limitations méthodologiques majeures. Afin d’élucider cette question, on a comparé les effets de l’huile de palme aux effets de l’huile d’olive sur l’homéostasie du glucose et d’autres paramètres métaboliques pertinents. Dans ce but, on a utilisé un modèle murin d’obésité induite par un régime riche en graisse. L’huile de palme est riche en acides gras saturés et elle est l’huile la plus utilisée globalement. L’huile d’olive est un aliment phare du régime Méditerranéen, riche en acides gras monoinsaturés et généralement reconnu comme un aliment sain. Dans notre modèle murin, la consommation d’huile de palme n’était pas plus néfaste que celle de l’huile d’olive sur l’homéostasie du glucose, la sensibilité à l’insuline et l’insulinosécrétion. Par contre, l’huile de palme était associée à une adiposité viscérale et une triglycéridémie plus élevée comparée à l’huile d’olive.La concentration et la composition des acides gras libres (AGL) sont déterminées par des facteurs alimentaires, génétiques et métaboliques. Des données abondantes démontrent que la présence des niveaux élevés d’AGL et/ou d’une composition déséquilibrée d’AGL induit la dysfonction et l’apoptose des cellules β (lipotoxicité). Pour caractériser les mécanismes sous-jacents de la lipotoxicité, on a combiné un séquençage ARN à une étude protéomique des cellules β exposées au palmitate, l’AGL saturé le plus courant chez l’homme. Cette étude conjointe a montré que le palmitate altère le métabolisme des lipides et des acides aminés, les voies d’amplification de la sécrétion d’insuline et l’exocytose. Le palmitate induit également des voies de stress cellulaires, telles que la dysfonction mitochondriale, le stress oxydatif et le stress du réticulum endoplasmique (RE). Le stress du RE est activé quand les besoins en sécrétion protéique dépassent les capacités de l’organite. Cette réponse a pour but de rétablir l’homéostasie du RE mais si le stress reste non résolu, ceci peut s’avérer délétère. Des îlots des patients avec un DT2 montrent des signes de stress du RE, évoquant un rôle potentiellement pathogénique de ce dernier.Le diabète monogénique et néonatal sont des formes rares de diabète causées par des mutations d’un seul gène. Ces formes sont particulièrement intéressantes sur le plan physiopathologique car elles représentent des ‘knockout’ humains. Des données récentes montrent que la base génétique du diabète monogénique n’est pas complètement distincte de celle du diabète de type 2 et les deux entités pourraient faire partie d’un continuum. Afin d’explorer le rôle du stress du RE dans la pathogénèse du diabète, on a étudié deux syndromes génétiques entraînant un diabète néonatal ou à début très précoce. Ces syndromes sont causés par des mutations dans des gènes impliqués dans la fonction du RE (DNAJC3 et YIPF5). En silençant ces gènes in vitro, on a montré que le stress du RE, déclenché soit par une dysfonction des chaperones (DNAJC3), soit par un retard du trafic de protéines du RE vers le Golgi (YIPF5), induit l’apoptose des cellules β.Ces résultats suggèrent que le stress du RE génétique et lipotoxique contribuent à la pathogénèse du diabète. La prévention ou modulation du stress du RE présente donc un potentiel thérapeutique anti-diabétique. Des études futures pourraient permettre de définir des stratégies optimales pour rétablir un profil d’AGL équilibré ou renforcer la fonction du RE, en vue de prévenir la défaillance des cellules β. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

Detta arbete undersöker förhållandet mellan kvalitetsparametrar i frityrolja, såsom halten fria fettsyror (FFA), anisidinvärdet (AV) och %TPM (Total Polar Materials) samt Agtronvärdet hos köttbullar efter fritering. Kvalitetsparametrar hos frityrolja, såsom primära och sekundära oxidationsprodukter, kan mätas för att utvärdera oljans kvalitet då nivåerna ofta ökar i samband med oljans användning. Primära oxidationsprodukter, såsom peroxider, kan mätas med hjälp av ett så kallat peroxidvärde (PV) och sekundära oxidationsprodukter, såsom aldehyder, kan mätas med hjälp av anisidinvärdet. Analys av %TPM och FFA är exempel på andra metoder för att mäta kvaliteten hos en olja då polariteten ökar i takt med oljans användning. Halten FFA i oljan undersöktes med hjälp av titrering med natriumhydroxid och %TPM mättes med hjälp av mätinstrumentet Testo 270. Agtronvärdet hos köttbullarna mättes med hjälp av instrumentet Agtron E30FP, som använder IR-teknologi för att bestämma färgen på en produkt. Resultaten visade att halten FFA, AV och %TPM i frityroljan ökade med tiden under samtliga fyra produktionsdagar. Hypotesen att produkten bör vara mörkare, det vill säga att Agtronvärdet bör vara lägre vid produktionens slut jämfört med början stödjs av resultaten från två av fyra produktionsdagar. Slutsatsen drogs att det fanns skillnader i oljans sammansättning, med hänsyn till FFA, AV och %TPM vid produktionsdagens slut jämfört med start. Däremot kunde ingen tydlig koppling ses mellan dessa förändringar och en minskning av Agtronvärdet hos köttbullarna över tiden. Ytterligare studier behövs således för att kunna dra en slutsats kring sambandet mellan kvalitetsparametrar i frityrolja och färgen på det friterade livsmedlet. / This study examines the relationship between quality parameters of frying oil, such as Free fatty acids (FFA), the Anisidine Value (AV) and Total Polar Materials (%TPM), as well as the Agtron Value of meatballs after deep frying. Quality parameters in frying oil, such as primary and secondary oxidation products, measure the quality of the frying oil since levels increase with the use of the oil. Primary oxidation products, such as peroxides, can be measured by the Peroxide Value (PV) and secondary oxidation products, such as aldehydes, can be measured by the Anisidine Value. Analysis of %TPM and FFA are other methods to measure the quality of an oil, since the polarity increases as the oil is used for frying. The instrument Testo 270 was used to measure %TPM in the oil and FFA was determined by titration with sodium hydroxide. The Agtron E30FP instrument was used to determine the Agtron Values of the meatballs, wich used IR technology to determine the color of the product. Results showed that the FFA, AV and %TPM of the oil increased over time in all four production days. It was expected that the product should be darker, that is, the Agtron Value should be lower at the end of production compared to the beginning, but this was only seen in two out of four production days. It was concluded that there are differences in the composition of the oil, with regard to FFA, AV and %TPM at the end of the production day compared to the beginning of the day, but no clear connection was seen between these changes and a decrease in the Agtron Value of the meatballs over time. Further studies are needed to be able to draw a conclusion about the relationship between quality parameters of frying oil and the color of the fried food.

No description available.