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Orientador: Jose Roberto Bosqueiro / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-11T17:39:01Z (GMT). No. of bitstreams: 1 Quallio_Silvana_M.pdf: 957537 bytes, checksum: 0c375a9b9290585b85244a414a6ea02d (MD5) Previous issue date: 2008 / Resumo: Introdução e objetivos: O aumento nos níveis de glicose circulante é o principal estímulo para a secreção de insulina. A insulina se liga a receptores de membrana desencadeando diversas respostas celulares. Qualquer alteração na sensibilidade à insulina pode levar a disfunções fisiológicas como a resistência à insulina observada em pacientes diabéticos tipo 2 (T2DM). Experimentalmente, essa condição patológica pode ser mimetizada pela administração de altas doses de glicocorticóides, provendo assim um bom modelo para seu estudo. O objetivo do presente trabalho foi avaliar a plasticidade das ilhotas pancreáticas submetidas à variação na necessidade secretória de insulina por indução de resistência periférica ao hormônio por tratamento com dexametasona e posterior interrupção do tratamento. Métodos: Ratos wistar com 90 dias de vida foram tratados com dexametasona (1mg/kg, ip) por 5 dias consecutivos (DEX). Em outro grupo (DEX10), os animais foram tratados da mesma maneira e avaliados 10 dias após o último dia da administração de dexametasona. Ratos controle (CTL) receberam administração de NaCl 0,9% apenas. As ilhotas foram isoladas pelo método da colagenase. A expressão de proteínas foi feita por immunoblotting. As análises morfométricas foram realizadas microscopicamente. Resultados: O grupo DEX exibiu marcante resistência periférica à insulina, que foi revertida após o período de 10 dias no grupo DEX10. As ilhotas do grupo DEX apresentaram alterações funcionais e morfológicas como aumento da secreção de insulina estimulada por secretagogos, da área, da densidade e tendência de aumento na massa de células ß ao contrário do grupo DEX10. O conteúdo de proteínas relacionadas ao ciclo celular como a CD2 e CDK4 e a fosforilação da AKT aumentou em ilhotas do grupo DEX, mas retornou aos níveis do CTL em ilhotas DEX10. Conclusão: Estes resultados mostram a plasticidade do pâncreas endócrino haja vista a habilidade de se adaptar a situações que exigem maior ou menor demanda de insulina / Abstract: Introduction and aims: Insulin binds to plasma membrane receptors leading to a variety of cellular responses. Malfunction in any of the insulin cell signalling pathways in target tissues may lead to several conditions and diseases, like hyperglycemia, insulin resistance and type 2 diabetes mellitus (T2DM). These effects may be experimentally reproduced using high doses of glucocorticoids, providing thus a good model for the study of T2DM. The aims of this study were to evaluate the plasticity of pancreatic islets subject to variation on the need for insulin secretory induction of peripheral resistance to the hormone by treatment with dexamethasone and subsequent treatment interruption. Methods: Male wistar rats (90 days old) were treated with dexamethasone (1mg/kg, ip) for 5 consecutive days (DEX). In another group (DEX10), the animals were treated in the same way and assessed 10 days after the last day of administration. Control rats (CTL) received equivalent volume of vehicle. Protein expression was assayed trough immunoblotting. Morphometric analyses were done using a optical microscope and specific digital analysis programs. Results: DEX group showed marked peripheral insulin resistance, reverted after the recovering period in the DEX10 group. DEX islets showed functional and morphological changes, like increased insulin secretion, superficial area, population density, and a tendency for increase in the total mass content of beta cell. Cell cycle proteins CD2 and CDK4 and AKT phosphorylation were increased in the DEX group when compared to CTL group. All these effects were reverted in the group DEX10. Conclusions: These results show that the endocrine pancreas possess a plasticity regarding the capacity of pancreatic islets to adapt themselves to situations where a higher or lower demand for insulin is needed. / Mestrado / Fisiologia / Mestre em Biologia Funcional e Molecular

Patients undergoing elective surgery typically fast for 8-12 hours before surgery. However, oral preoperative carbohydrate ingestion may increase postoperative insulin sensitivity and reduce complications. To determine the effects of carbohydrate supplementation prior to CABG or spinal surgery, 38 patients were randomized to receive a carbohydrate supplement or to fast for 12 hours preoperatively. Baseline and postoperative measurements of insulin sensitivity were completed using the short insulin tolerance test and homeostasis model assessment (HOMA). Patient discomfort was measured immediately before surgery. Insulin sensitivity was not significantly different between groups. However, the supplemented group experienced a significantly smaller rise in glucose levels following surgery (p=0.03) and had higher postoperative HOMA-β scores (p=0.02). Fasted patients were significantly more thirsty (p=0.01), hungry (p=0.04) and anxious (p=0.01) before surgery and experienced a significantly longer hospital stay (p=0.008). Carbohydrate supplementation improved outcomes, warranting re-evaluation of fasting practices prior to major surgery.

Patients undergoing elective surgery typically fast for 8-12 hours before surgery. However, oral preoperative carbohydrate ingestion may increase postoperative insulin sensitivity and reduce complications. To determine the effects of carbohydrate supplementation prior to CABG or spinal surgery, 38 patients were randomized to receive a carbohydrate supplement or to fast for 12 hours preoperatively. Baseline and postoperative measurements of insulin sensitivity were completed using the short insulin tolerance test and homeostasis model assessment (HOMA). Patient discomfort was measured immediately before surgery. Insulin sensitivity was not significantly different between groups. However, the supplemented group experienced a significantly smaller rise in glucose levels following surgery (p=0.03) and had higher postoperative HOMA-β scores (p=0.02). Fasted patients were significantly more thirsty (p=0.01), hungry (p=0.04) and anxious (p=0.01) before surgery and experienced a significantly longer hospital stay (p=0.008). Carbohydrate supplementation improved outcomes, warranting re-evaluation of fasting practices prior to major surgery.