Made available in DSpace on 2015-12-06T23:05:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2005 / Objetivo: detectar as alterações macroscópicas e microscópicas do mesentério e do peritônio parietal, quando se administra a solução aquosa de glicose hipertônica a 10% e a 25% na cavidade peritoneal de rato. Métodos: Utilizou-se as amostras de 90 ratas (n=90) “Wistar”, adultas jovens, variando entre 180 – 250 g e enumeradas de 1 a 90, constituindo grupo único e distribuído aleatoriamente em três sub-grupos: A, B e C, contendo cada sub-grupo 30 animais com procedimentos idênticos diferindo apenas no período de observação: 6h; 24h; 48h. Em todos os animais praticou-se incisão longitudinal de pele na linha média ventral. As ratas do sub-grupo A ou grupo-controle, receberam 2 ml de uma solução de cloreto de sódio a 0,9% (NaCl 0,9%) distribuída diretamente na cavidade peritoneal. Usou-se, para isso, seringas descartáveis de 3 ml e posteriormente, seguiu-se de uma síntese em massa da parede abdominal anterior com fio de mononylon 3-0 e excluiu-se o peritônio parietal. Para as ratas dos grupos B e C, (grupo-glicose 10% e grupo-glicose 25%) respectivamente, realizou-se a introdução de 2 ml de soluções de glicose a 10% e 25% na cavidade peritoneal com síntese em massa das paredes abdominais, semelhantes a do grupo A. Resultados: Esses animais foram reoperados nas 6h, 24h e 48h e definiu-se a avaliação macroscópica. Na cavidade peritoneal, observou-se a presença de líquido com uniformidade da serosa e com coloração rósea em toda extensão da área e local estudado. Evidenciou-se presença de congestão vascular. Completou-se a retirada de 90 fragmentos de mesentério e 90 fragmentos de peritônio parietal bilateralmente, totalizando 180 fragmentos. Nenhum animal apresentou necrose e na microscopia do mesentério, as alterações histológicas foram assim distribuídas: 16 casos (17,8%) com inflamação crônica inespecífica; 30 casos (33,4%) com linfonodos hiperplásicos; 10 casos (11,1%) com intensa congestão vascular; 6 casos (6,6%) com fibrose reacional e 28 casos (31,1%) sem alteração, além de ausência de células gigantes, comprovouse uma reação inflamatória de leve intensidade. Nas alterações microscópicas do peritônio parietal, apenas 6 casos apresentaram fibrose reacional (3,3%). Os demais, sem alteração histológica (96,7%). Na análise estatística, não há existência de diferença significativa entre os grupos analisados e as alterações observadas (p>0,05). Conclusões: Concluiu-se, portanto, com base na presente pesquisa, que o uso das soluções de glicose hipertônica e de cloreto de sódio a 0,9% no mesentério e no peritônio parietal não causa necrose tecidual e que o processo inflamatório é de igual intensidade. / Purpose: The objective is to detect the macroscopic and microscopic alterations of the mesenterium and parietal peritoneum when hypertonic glucose aqueous solution 10%- 25% is administrated into the peritoneal cavity of the rat. Methods: Were used 90 Wistar females young rats with weight between 180-250 g, enumerated of 1 to 90, establishing unique group and divided in three groups (A, B, C) of 30 animals chosen aleatory manner. Was used 0,9% saline solution called control group, or group A, 10% glucose solution named group B, and in the others 30 was used 25% glucose solution named group C, differing as soon as in the observation period, (06h, 24h and 48h), but with the same procedure. Was realized a midline abdominal laparotomy wall and in the animals of the control group was injected 2 ml of a 0,9% saline solution into the peritoneal cavity. After, we made a suture in mass without to include the peritonium for the others groups (B, C) the rats received 10% glucose solution and 25% glucose solution injected into the peritoneal cavity respectively. Results: A new surgery was realized in 6h, 24h and 48h, and we observed in macroscopic avaluation presence of fluid and serous uniforme and rosy in all over the cavity. The vascular congestion was present. We made dry out of 90 fragments of mesenterium and 90 fragments of parietal peritonium bilateral. In the microscopic study necrosis doesn´t was present. For the mesenterium histological study we observed 16 cases (17,8%) unspecific chronic inflammation, 30 cases (33,4%) hiperplasic linfonod, 10 cases (11,1%) high vascular congestion, 6 cases (6,6%) reaction fibrosis and 28 cases (31,1%) no alteration. For the parietal peritonium histological study we observed 6 cases (3,3%) reaction fibrosis and 174 cases (96,7%) no alteration. Giant cell was not present. In the analisys statistic there is no significance between the groups (p>0,05). Conclusions: So, we concluded, according to the present research, that hypertonic glucose solution and NaCl 0,9% on the mesenterium and parietal peritonium don´t produce tissue necrosis in a rat`s model and the inflammation process has the same intensity / BV UNIFESP: Teses e dissertações

The goal of this research project is to understand how a high sugar diet may affect pancreatic beta cell function. High glucose concentrations lead to an increase in lipid droplets and TORC1 in beta cells, which promote high basal secretion of insulin (Erion K.A. et al., JBC, 2015). SREBP is a key regulator of cholesterol and lipid synthesis and depends on TORC1 activity. The active form of SREBP is located in the nucleus. Does glucose-induced lipid synthesis in beta cells increase via SREBP? To answer this question, we propose: 1) To test the effect of high glucose (11mM) on nuclear SREBP in INS-1 cells in comparison to physiological glucose (4mM). 2) To determine if nuclear SREBP is affected when PIP4Kgamma (a regulator of TORC1) is suppressed. SREBP translocation from the cytosol to the nucleus was measured by immunofluorescence. SREBP processing was measured by western blot. SREBP1 activation increased in response to prolonged exposure to excess glucose after at least 48hrs. Both translocation and processing increased in 11mM glucose compared to 4mM glucose. When PIP4Kgamma was suppressed in INS-1 cells, SREBP translocation was inhibited. Lipid droplet accumulation was measured by nile red staining and it was found that de novo lipid synthesis only contributes to a small fraction of total lipid droplets. In conclusion, SREBP is activated in beta cells when in excess glucose. This may allow for lipid accumulation and basal hypersecretion of insulin due to over nutrition.

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O metabolismo cerebral é altamente dependente da glicose, que é derivada a partir da circulação sanguínea e metabolizada pelos astrócitos e outras células neuronais, através de várias vias. A captação da glicose no cérebro não envolve transportadores de glicose insulino-dependentes; no entanto, esse hormônio afeta o fluxo de glicose do cérebro. Alterações nos níveis de S100B (uma proteína derivada de astrócitos) no líquido cefalorraquidiano têm sido associados a alterações no metabolismo da glicose; no entanto, não há evidência que a insulina modula o metabolismo da glicose e a secreção de S100B. Investigamos então o efeito da S100B no metabolismo da glicose, medindo a incorporação de 3H-glicose em dois modelos, em células de glioma C6 e fatias hipocampais agudas, investigando o efeito da insulina sobre a secreção de S100B. Os nossos resultados mostram que: (a) a S100B em níveis fisiológicos diminui a captação de glicose, através da via do receptor multiligante RAGE e através da ativação da via de sinalização da proteína-quinase / ERK, e que (b) insulina estimulada a secreção de S100B via sinalização de PI3K. Os nossos resultados indicam a existência de uma relação insulina-S100B na modulação de glicose no tecido cerebral, o que pode melhorar a nossa compreensão sobre o metabolismo da glicose em várias condições, tais como a cetose, demência induzida por estreptozotocina e exposição farmacológica aos antipsicóticos, onde as mudanças de sinalização da insulina e extracelular celular de S100 foram relatados. / Brain metabolism is highly dependent on glucose, which is derived from the blood circulation and metabolized by the astrocytes and other neural cells via several pathways. Glucose uptake in the brain does not involve insulin-dependent glucose transporters; however, this hormone does affect the brain’s glucose in flux. Changes in cerebrospinal fluid levels of S100B (an astrocyte-derived protein) have been associated with alterations in glucose metabolism; however, there is no evidence as to whether insulin modulates glucose metabolism and S100B secretion. Herein we investigated the effect of S100B on glucose metabolism, measuring 3H-glucose incorporation in two preparations, C6 glioma cells and acute hippocampal slices, and we also investigated the effect of insulin on S100B secretion. Our results showed that: (a) S100B at physiological levels decreases glucose uptake, through via the multiligand receptor RAGE and mitogen-activated protein kinase/ERK signaling, and that (b) insulin stimulated S100B secretion via PI3K signaling. Our findings indicate the existence of insulin-S100B modulated glucose utilization in the brain tissue, and may improved our understanding of glucose metabolism in several conditions such as ketosis, streptozotocin-induced dementia and pharmacological exposure to antipsychotics, where changes of insulin signaling and extracellular cellular of S100 have been reported.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by beta-amyloid (Abeta) deposition, neurofibrillary tangles and cognitive decline. Clinical data suggest that diabetes may be a risk factor for AD and several studies have linked pro-diabetic diets with an acceleration of AD pathology. Consequently, we hypothesized that the 3xTg AD-like mouse model may show impaired glucose tolerance, therefore; we examined whether glucose tolerance was altered in the 3xTg mouse model of AD early in the pathogenesis (prior to Abeta plaques, neurofibrillary tangle sand cognitive decline) and if so, did it persist throughout. Specifically, 1, 2-3, 4-6, 8-10 and 17 month old male 3xTg mice and wild-type counterparts were assessed for fasting glucose levels, glucose tolerance, plasma insulin levels, insulin sensitivity and the neural and behavioral pathological characteristics of AD. At 1 month, 3xTg mice compared to wild-type controls exhibited impaired glucose tolerance during an intraperitoneal glucose tolerance test (ipGTT), a trend for reduced fasting plasma insulin levels at time 0 and significantly reduced fasting plasma insulin levels 15 minutes post glucose bolus suggesting a possible defect in beta cell function. Interestingly, the glucose intolerance was not a consequence of altered food intake or body weight since these parameters were similar between the 3xTg mice and wild-type controls. Moreover, responsiveness to exogenous insulin during the intraperitoneal insulin tolerance test was not significantly different suggesting equivalent insulin sensitivity. During aging both 3xTg mice and controls exhibited exacerbated changes in fasting glucose levels and glucose tolerance. Interestingly, while control animals show an increase in fasting insulin levels with age, 3xTg mice do not. Immunohistochemical staining for 6E10 and Abeta 1-42 revealed only intraneuronal deposition of reaction product in 3xTg mice with no extracellular depositions noted until 14 months of age. Immunoreactivity of p-tau was observed at 1 month in the hippocampus and cortex and worsened throughout the time period examined. Behavioral deficits began to be detected in 3xTg mice relative to wild-type controls at 21 months of age. The islets in the pancreas suggest that at 2-3 months of age 3xTg mice compared to wild-type controls have a significantly lower amount of immunoreactivity for insulin within their islets although islet size did not differ between groups and this persisted throughout all the time points examined (4-6 and 8-10 months). Taken together, these data reveal that the AD-like 3xTg mouse model exhibits a pro-diabetic phenotype early in the development of AD-like pathology and that this metabolic deficit persists throughout their lifespan raising the question of whether altered glucose regulation and insulin production/secretion could contribute to AD pathogenesis.

Made available in DSpace on 2015-12-06T23:47:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2007 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / BV UNIFESP: Teses e dissertações

The thesis is divided into two parts, which in turn are subdivided as follows: Account of the various methods for the preparation of glucosan. Proof of the constitution of glucosan, together with the general problem of its relationship to starch and cellulose. An investigation of the acid products obtained during the methylation of glucosan by means of silver oxide and methyl iodide. And: An investigation of the conditions necessary for the polymerisation of glucosan, and of the properties and constitution of the products.

After discussing the condensation portion of methylglucoside with benzaldehyde and the chemistry of the product, the structure of benzylidene methylglucoside, together with that of the dimethyl glucose, is reviewed. A few observations upon the effect of the substitutions upon the molecular rotation of methylglucoside is then inserted before an account is given of the chemical behaviour of dimethyl glucose, as contrasted with that of the unsubstituted sugar. Finally, the experiments on which the Thesis is based, prefaced by notes explaining the technique adopted, complete the work.

The condensation of simple aliphatic and aromatic aldehydes and of ketones with cyclic and acyclic glucose derivatives has been considerably investigated and, thus, isopropylidene, ethylidene, benzal and many similar and related compounds are well known: for example, benzaldehyde condenses readily with methyl glucoside and this typical reaction may be illustrated by the equation which is formulated on the following page. It is, therefore, a continuation of this work to attempt to effect similar condensations employing, as the carbonyl component, open-chain sugar derivatives which possess a free aldehydic group and to determine whether such ‘glucosydlidene' compounds are available.