Made available in DSpace on 2017-07-10T14:17:14Z (GMT). No. of bitstreams: 1 Dissertacao_ final - ENTREGA.pdf: 2247856 bytes, checksum: 146d4be3628d74a867ddf4826f6f6e8a (MD5) Previous issue date: 2015-07-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Purpose: Herein we evaluated the expression of genes and protein involved with hepatic lipids pathway and investigate whether the improvement on glucose homeostasis is associated with modifications in the islets morphology in HyO rats submitted to duodenal-jejunal bypass (DJB). Methods: During the first 5 days of life, male newborn Wistar rats received a subcutaneous injection of monosodium glutamate [4 g/kg body weight (BW), hypothalamic obesity (HyO) group], or saline (CTL group). At 90 days of age, HyO rats were submitted to DJB or sham operations forming HyO DJB and HyO Sham group, respectively. Two months after DJB, serum parameters, expression of genes and protein in the liver and islets morphology were verified. Results: Although DJB operation normalized serum triglycerides (TG) and non-esterified fatty acids (NEFA) concentration compared to HyO Sham rats, HyO DJB rats did not alter TG liver content as well as, the expression of hepatic genes and protein involved with lipids metabolism. DJB operation normalized insulinemia and insulin resistance and restored β-cell secretion in the presence of 8.3 mM glucose independently of weight loss. In addition, HyO DJB rats presented a reduction in total islets and β-cell area (pancreas area percentage) and in islets cells proliferation (verified by the number of nucleus stained by Ki67 protein - a cellular marker for proliferation). Conclusions: Although DJB not affect liver lipids metabolism in HyO rats two months after surgery, the improvement on glucose homeostasis could be associated with modifications in islets morphology and proliferation. / Objetivo: Avaliar a expressão de genes e proteínas envolvidos com a via lipídica hepática e investigar se a melhoria na homeostase glicêmica está associada a alterações na morfologia das ilhotas em ratos MSG submetidos à derivação duodeno-jejunal (DDJ). Métodos: Durante os primeiros 5 dias de vida, ratos Wistar recém-nascidos receberam injeções subcutâneas de glutamato monossódico [4 g / kg de peso corporal (BW), grupo MSG], ou solução salina (grupo CTL). Aos 90 dias de idade, os animais MSG foram submetidos à DDJ ou a falsa operação, formando os grupos MSG-DDJ e MSG-FO, respectivamente. Dois após a cirurgia, foram avaliados os parâmetros séricos, a expressão de genes e proteínas do fígado e morfologia das ilhotas pancreáticas. Resultados: A cirurgia de DDJ normalizou as concentrações de triglicerídeos séricos (TG) e dos ácidos graxos não-esterificados em comparação aos animais MSG-FO, porém não alterou o conteúdo de TG no fígado, bem como, a expressão de genes e proteínas hepáticas envolvidas com o metabolismo lipídico. Além disso, a DDJ normalizou a insulinemia e a resistência à insulina, e restaurou a secreção de insulina pelas células-β na presença de 8,3 mM de glicose, independentemente da perda de peso. Ainda, ratos MSG-DDJ apresentaram redução nas áreas totais da ilhota e de células β (% área pâncreas) e na proliferação de células da ilhota (verificado pelo número de núcleos corados por Ki67). Conclusões: A cirurgia de DDJ não alterou o metabolismo lipídico no fígado, dois meses após a realização da cirurgia, sendo assim, a melhora na homeostase glicêmica nos animais pode estar associada a alterações na morfologia e proliferação das ilhotas pancreáticas

Made available in DSpace on 2017-07-10T14:17:16Z (GMT). No. of bitstreams: 1 GABRIELA_ MOREIRA SOARES.pdf: 1940590 bytes, checksum: 743251bbcf008feeceea6700678f7e3f (MD5) Previous issue date: 2016-01-30 / Fundação Araucária / Hypothalamic obesity (HyO) is a severe condition without any effective therapy. Bariatric operations appear as an alternative treatment, but the effects of this procedure are controversial. Here, we investigated the effects of duodenal-jejunal bypass (DJB) upon lipid profile and expression of main genes, protein and transcription factors involved in hepatic lipid metabolism pathways in HyO rats. During the first 5 days of life, male newborn Wistar rats received a subcutaneous injection of monosodium glutamate (MSG) [4 g/kg body weight (BW), HyO group]. Control (CTL) group received saline [1.25 g/kg BW]. At 90 days of age, HyO rats were randomly submitted to DJB or sham operations forming HyO DJB and HyO Sham group, respectively. Six months after DJB, obesity parameters, lipids levels, and expression of genes and protein in the liver were verified. HyO Sham rats displayed obesity, hyperinsulinemia, insulin resistance, hypertryglyceridemic and presented higher free fatty acids (FFA) levels and hepatic triglyceride (TG) content. Also, HyO Sham animals enhanced acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN) and stearoyl-CoA desaturase-1 (SCD-1) mRNA levels and ACC and FASN protein in the liver. Carnitine palmitoyltransferase-1a (CPT-1a) and microsomal TG transfer protein (MTTP) were down-regulated in HyO Sham rats. DJB operation normalized serum insulin, TG and FFA levels and hepatic TG content, without changing obesity in these animals. In addition, DJB reduced mRNA levels of liver pyruvate kinase (LPK), ACC, SCD-1, acyl-CoA oxidase (ACO) and carbohydrate response elemento-binding protein (ChREBP). ACC and FASN protein expression were normalized in HyO DJB animals. DJB reduces de-novo lipogenesis and improves hepatic TG content in HyO DJB rats, indicating that this surgery is efficient in the resolution of nonalcoholic fatty liver disease (NAFLD) in HyO. / A obesidade hipotalâmica (OH) é uma condição severa que não apresenta nenhuma terapia eficaz. Cirurgias bariátricas têm surgido como uma alternativa de tratamento, porém, os efeitos deste procedimento são controversos. No presente trabalho, investigamos os efeitos da derivação duodeno-jejunal (DDJ) sobre o perfil lipídico e sobre a expressão gênica de proteínas e fatores de transcrição envolvidos em vias do metabolismo lipídico hepático em ratos com OH. Durante os cinco primeiros dias de vida, ratos Wistar neonatos receberam uma injeção subcutânea de glutamato monossódico (MSG) [4 g/kg de peso corporal, grupo OH]. O grupo controle (CTL) recebeu solução salina [1,25 g/kg de peso corporal]. Aos 90 dias de idade, os ratos OH foram aleatoriamente submetidos à pseudo-cirurgia (PC) ou à DDJ, formando os grupos OH PC e OH DDJ, respectivamente. Seis meses após a DDJ, foram verificados, os parâmetros de obesidade, concentração de lipídios e expressão gênica e proteica no fígado. Ratos OH PC apresentaram obesidade, hiperinsulinemia, resistência à insulina, hipertrigliceridemia, concentrações elevadas de ácidos graxos livres (AGL) e do conteúdo de triglicerídeo (TG) hepático. Também, os animais OH PC tiveram aumento na quantidade de mRNA da acetil-CoA carboxilase (ACC), ácido graxo sintetase (FASN) e estearoil-CoA desaturase-1 (SCD-1) e da expressão proteica da ACC e FASN no fígado. A expressão gênica da carnitina palmitoil-transferase-1a (CPT-1a) e da proteína de transferência de triglicerídeos microssomal (MTTP) foram menores no fígado do grupo OH PC. A cirurgia de DDJ normalizou a concentração de insulina, AGL e TG séricos e o conteúdo de TG hepático, sem alterar a obesidade nesses animais. Além disso, a DDJ reduziu a expressão do mRNA da piruvato quinase hepática (LPK), ACC, SCD-1, acil-CoA oxidase (ACO) e da proteína de ligação do elemento responsivo à carboidratos (ChREBP). A expressão proteica de ACC e FASN foi normalizada em animais OH DDJ. A DDJ reduz a lipogênese de novo e melhora o conteúdo de TG hepático em ratos OH DDJ, indicando que esta cirurgia é eficiente na resolução da doença hepática gordurosa não alcoólica (DHGNA) na OH.

Made available in DSpace on 2016-08-17T18:39:50Z (GMT). No. of bitstreams: 1 5711.pdf: 887082 bytes, checksum: 2f6dabfb50d2965eaa1d19f975e6a2e7 (MD5) Previous issue date: 2012-11-21 / Financiadora de Estudos e Projetos / Sorghum is increasingly being used for animal feed replacing corn, due to their similar nutritional characteristics, but with a lower cost. However one factor that negatively influences the nutritional value of sorghum is the presence of tannin that is an anti-nutritional factor that affects the nutrients absorption by the animal. We evaluated the effect of the sorghum with high and low tannins concentrations and / or the addition of tannic acid in diets based on corn and soybean on the single jejunal (duodenum, jejunum and ileum) histomorphometric parameters in broilers. There were used 150 male chicks with 1 day old of Cobb lineage, they were created up to 42 days in cages, in a controlled environment and receiving isoproteic and isoenergetic diets. After the period, were collected fragments of the 3 single jejunal segments, where they were measured and analyzed through a microscope with a coupled camera, according with the established parameters (villus height, crypt depth, thickness of muscle layer and relationship between villus numbers and villus bifurcations numbers). The addition of tannin in diets caused histomorphometric modifications in all parameters, but they did not cause significant changes for affecting their productive performance, such as weight and carcass yield. / O sorgo vem sendo cada vez mais utilizado para alimentação animal em substituição ao milho, devido suas características nutricionais semelhantes, porém com um custo muito menor. No entanto um fator que influencia negativamente o valor nutricional do sorgo é a presença de tanino, um fator antinutricional que compromete a absorção de nutrientes pelo animal. Avaliou-se o efeito do sorgo com alto e baixo teor em taninos e/ou a adição do ácido tânico em dietas à base de milho e soja, sobre os parâmetros histomorfométricos do intestino delgado (duodeno, jejuno e íleo) em frangos de corte. Foram utilizados 150 pintos machos de 1 dia de idade da linhagem Cobb, criados até aos 42 dias de idade em gaiolas, em ambiente controlado e recebendo rações isoprotéicas e isoenergéticas. Após o período foram coletados fragmentos dos 3 segmentos do intestino delgado, onde foram analisados e mensurados através de um microscópio com câmera acoplada, de acordo com os parâmetros estabelecidos (altura de vilosidade, profundidade de cripta, espessura de camada muscular e relação entre números de vilosidades e números de bifurcações) . A adição de tanino nas dietas causou modificações histomorfométricas em todos os parâmetros avaliados, porém essas modificações não ocasionaram alterações significativas para que comprometessem o desempenho produtivo das aves, como peso e rendimento de carcaça.

Made available in DSpace on 2017-07-10T14:17:07Z (GMT). No. of bitstreams: 1 Claudia Ebertz.pdf: 1969807 bytes, checksum: 61f18bbc24e26e53d1b8941d93aadc58 (MD5) Previous issue date: 2013-12-17 / Purpose: Bariatric surgeries reduce non-alcoholic fatty liver disease (NAFLD), which is associated with metabolic syndrome co-morbidities; however, the effects of duodenal-jejunal bypass (DJB) have not been investigated. This study aimed to evaluate the effects of DJB on serum and hepatic profiles of obese rats fed on a western diet (WD). Methods: Male Wistar rats were fed a standard rodent chow diet (CTL group) or WD ad libitum. After 10 weeks, WD rats were submitted to sham (WD SHAM) or duodenal-jejunal bypass (WD DJB). Body weight, fat pad depots, glycemia, insulinemia, HOMA-IR, TyG, lipids profile and hepatic analyses were evaluated two months after surgery. Results: The WD SHAM group presented greater obesity, hyperglycemia, hyperinsulinemia, insulin resistance, hypertriglyceridemia and hepatic steatosis than the CTL group. WD DJB rats presented decreased serum glucose and insulin resistance, when compared to WD SHAM animals, without changes in insulinemia. In addition, DJB surgery normalized serum TG and attenuated TG accumulation and steatosis in the liver of the WD DJB group. Hepatic ACC and FAS protein expressions were similar in all groups. Conclusions: DJB attenuates hepatic parameters of NAFLD in obese rats fed on a WD diet / Introdução: Cirurgias bariátricas reducem a doença hepática gordurosa não alcoólica (DHGNA), a qual está associada a comorbidades da síndrome metabólica, entretanto, os efeitos da derivação duodeno-jejunal (DDJ) não foram investigados. Este estudo tem por objetivo avaliar os efeitos da DDJ no perfil sérico e hepático de ratos obesos submetidos à dieta de cafeteria. Métodos: Ratos Wistar foram alimentados com ração padrão para roedores (grupo CTL) ou dieta de cafeteria (grupo CAF) ad libitum. Após 10 semanas de dieta, os animais do grupo CAF foram submetidos à falsa cirurgia (CAF FO) ou à derivação duodeno-jejunal (CAF DDJ). O peso corporal, peso dos depósitos de gorduras, glicemia, insulinemia, HOMA-IR, índice TyG, perfil lipídico e análises hepáticas foram avaliados dois meses após a cirurgia. Resultados: O grupo CAF FC apresentou obesidade, hiperglicemia, hiperinsulinemia, resistência à insulina, hipertrigliceridemia e esteatose hepática em relação ao grupo CTL. Os animais CAF DDJ apresentaram diminuição da glicose sérica e resistência à insulina, sem alterações na insulinemia, quando comparados aos animais CAF FC. Além disso, a DDJ normalizou a concentração sérica de triglicérides e atenuou o acúmulo hepático de triglicérides, bem como a esteatose hepática no grupo CAF DDJ. A expressão proteica de ACC e FAS hepáticas foram similares nos três grupos. Conclusões: A DDJ atenuou os parâmetros hepáticos da DHGNA em ratos obesos por dieta de cafeteria

Chez les rongeurs rendus obèses par un régime hyper-lipidique, un changement du microbiote est associé à une altération de la perméabilité intestinale, augmentant le passage d’antigènes alimentaires ou bactériens et contribuant à une inflammation chronique de bas grade et une insulinorésistance. Cependant chez l’homme, les modifications de perméabilité intestinale, son impact sur les altérations métaboliques, inflammatoires systémiques et tissulaires sont peu documentées. L’objectif de ce travail est de caractériser la perméabilité intestinale (i.e. jéjunum) et les mécanismes impliqués dans sa régulation dans l’obésité humaine sévère en conditions de jeûne (basal) et après un apport aigu de lipides selon des approches complémentaires in vivo (biomarqueurs), ex vivo (chambre de Ussing, étude des protéines de jonctions serrées en immunofluorescence) et in vitro (lignée cellulaire Caco-2/TC7). A l’état basal nous avons observé une diminution de la localisation de l’occludine et de la tricelluline dans les jonctions serrées au niveau du jéjunum et des taux circulants en zonuline et LPS binding protéine plus élevés chez les obèses. La perméabilité Jéjunale basale mesurée ex vivo en chambre de Ussing était comparable entre obèses et non obèses avec cependant des liens entre ces mesures et les paramètres de l’inflammation systémique chez les patients obèses (CRP et Haptoglobine). Une charge unique en lipides alimentaires, entrainait une augmentation rapide et significative de la perméabilité aux macromolécules (FITC-Dextran 4 kDa) in vitro et ex vivo, démontrant ainsi l’effet direct des lipides postprandiaux sur la barrière épithéliale. La perméabilité aux macromolécules après exposition aux lipides était plus élevée chez les patients obèses à fortiori diabétiques de type 2 et était associée à l’inflammation systémique (CRP) et intestinale (calprotectine fécale). Ainsi, nos résultats mettent en évidence un défaut de la barrière intestinale dans l'obésité caractérisée par une hyperperméabilité jéjunale démasquée par les lipides alimentaires et associée à l’inflammation et aux troubles métaboliques. / Intestinal barrier damage is associated with low-grade inflammation and metabolic impairment in rodent models of obesity. Whether intestinal permeability is altered in human metabolic disorders remains poorly investigated. Using a large cohort of well-characterized obese subjects and a human enterocyte model, we examined intestinal permeability in the basal state and after a challenge by a lipid load. We showed a reduction of occludin and tricellulin at jejunal tight junctions and increased serum levels of zonulin and LPS-Binding Protein in obese subjects. Jejunal permeability, directly measured in Ussing chambers in the fasting condition, was not significantly increased compared to non-obese subjects. Nevertheless, within the obese cohort, high permeability was associated with systemic inflammation (CRP and haptoglobin). A single lipid load increased permeability both in Caco-2/TC7 cells and ex vivo in human jejunum, demonstrating dietary lipids’ direct effects on the epithelial barrier. Permeability after the lipid load was significantly higher in the jejunum of obese subjects and associated with systemic and intestinal inflammation (CRP and fecal calprotectin) and type 2 diabetes. Thus, our results highlight an intestinal barrier defect in obesity, with a jejunal permeability increased by a lipid challenge and linked to inflammatory and metabolic impairments.

Drugs exhibiting decreased extent of absorption in the fed state administration when compared to the fasted state administration are termed to exhibit a negative food effect. The known causes for negative food effects are luminal degradation and complexation to metal ions/Ca 2+ . For the drugs that do not undergo GI degradation and metal ion complexation, different factors were attributed to cause negative food effects, which are inconclusive. The objectives of this investigation were; to identify the physicochemical and physiological changes between fasted and fed states and their role in causing negative food effects; to develop an empirical model that correlates the biopharmaceutical properties of molecules to negative food effects; and translate the empirical model to a mechanistic model and explain the mechanisms of negative food effects for drugs that do not have clearly defined mechanisms of negative food effects. The important physicochemical change in the upper intestine was identified to be pH. The pH of the upper intestine in the fasted state is typically 6.5, whereas, the overall post-prandial pH after a standard meal in the duodenum is 5.4 (5.0 − 5.7) and the jejunal pH is 4.7 owing to the emptying of acidic chyme. Negative food effect drugs exhibited incomplete GI absorption, low Log P values and low apical to basolateral Caco-2 permeabilities. Acidic/basic drugs exhibiting either negative food effects or no food effects with a molecular size range of 200–450 Da and no physiological effects (such as secretions and motility) were selected from the literature. Multiple linear regression analysis using five drugs exhibiting negative food effects and seven drugs exhibiting no food effects indicated that, percent food effects correlated to acidic/basic dissociation constants (Ka/Kb) and to Caco-2 permeability (R 2 = 0.9114, Power ≈ 1 and p < 0.00002). A mathematical model, adopted to understand the mechanisms of negative food effects suggested that, lowering of permeability or solubility of the model compounds at the lower pH of the postprandial upper intestinal state may contribute to their negative food effects. Finally, this model was found to be useful in predicting negative food effects using in situ rat permeability values.

No description available.

Objectives: The study aim was to analyse the kinetics of stem and transit cells in the crypts of jejunal mucosa infected with HIV and Microsporidia. Design: The size of villi, depth of crypts and proliferative activity of transit and stem cells in jejunal mucosa were measured using morphometric techniques. Methods: The surface area/volume ratio (S/V) of jejunal biopsies was estimated under light microscopy using a Weibel graticule. Crypt length was measured by counting enterocytes along the crypt side from the base to the villus junction, and the mean crypt length was calculated. The S/V and crypt lengths of the jejunal mucosa of 21 HIV and Microsporidia-infected test cases were compared with 14 control cases. The labelling index in relation to the crypt cell position of 10 of the test cases was analysed compared with 13 control cases. Results: Differences were found in the S/V and crypt length, and there was a negative correlation between S/V and crypt length in test and control cases combined. Cell labelling indices fell into low and high proliferation groups. There were significant differences in labelling indices between low proliferation test cases and controls, between high proliferation test cases and controls, and between high and low proliferation test cases. Conclusion: Villous atrophy induced by HIV and Microsporidia is attributed to crypt cell hyperplasia and the encroachment of crypt cells onto villi. These infections induce crypt hypertrophy by stimulating cell mitosis predominantly in transit cells but also in stem cells. Increased stem cell proliferation occurs only in high proliferation cases.

Made available in DSpace on 2017-07-10T14:17:15Z (GMT). No. of bitstreams: 1 Disse Bruna_Hart Ulsenheimer - 2015.pdf: 2178215 bytes, checksum: 09b8e8a87e9abce53b52ac7a53bd9afb (MD5) Previous issue date: 2014-04-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Concerning obesity, the diaphragm dynamics can be impaired due to the excess of fat deposited in thorax and abdomen, leading to changes in respiratory function. A technique of bariatric surgery known as duodenal-jejunal bypasses (DJB) has been investigated as a treatment strategy in obesity and its comorbidities. However, the effects of this procedure on skeletal muscles have not yet been observed. The present study aimed at investigating the DJB effects on the neuromuscular junctions (NMJs) and muscle fibers of diaphragm of obese rats induced by cafeteria diet. Male Wistar rats were divided into two groups: a control group (CTL) that received a standard diet and water, and Western Diet group (WD) that received a cafeteria diet and soft drink for 10 weeks. After this period, WD group was distributed into two groups: WD sham-operated rats (WD SHAM); and WD DJB-operated rats (WD DJB). Following surgery, both the WD groups continued to receive the cafeteria diet. After eight weeks, the animals were euthanized and samples of diaphragm muscle were collected to analyze its fibers, quantify its collagen and evaluate NMJs morphometric. WD SHAM rats displayed an increase in body weight, the Lee index and retroperitoneal and peri-epididymal fat pads compared to the CTL group and DJB surgery did not alter these parameters. The muscle fiber structure and NMJs were similar in the WD SHAM and CTL groups. However, the WD SHAM group showed alterations in the fiber ultrastructure, such as loosely arranged myofibrils and Z line disorganization in the diaphragm. In addition, WD SHAM animals presented a considerable amount of lipid droplets and a reduction in the percentage of collagen in diaphragm muscle compared to the CTL group. DJB did not affect the structure or ultrastructure of the muscle fibers or the NMJs in the diaphragm of the WD DJB animals. Two months after the procedure, DJB did not improve the alterations observed in the diaphragm of WD obese-rats. / Na obesidade, a dinâmica do músculo diafragma pode ser prejudicada pelo excesso de tecido adiposo depositado no tórax e abdome, levando a alterações na mecânica respiratória. Uma técnica de cirurgia bariátrica conhecida como a derivação duodenojejunal (DDJ) tem sido investigada como estratégia de tratamento na obesidade e em suas comorbidades. Todavia, os efeitos desse procedimento sobre a musculatura esquelética ainda não foram observados. Assim, o presente estudo teve como objetivo investigar os efeitos da DDJ sobre as junções neuromusculares (JNMs) e nas fibras musculares do músculo diafragma de ratos obesos induzidos por dieta de cafeteria. Ratos Wistar machos foram separados em dois grupos: grupo controle (CTL) que recebeu dieta padrão e água, e grupo cafeteria (CAF) que recebeu dieta de cafeteria e refrigerante durante 10 semanas. Após este período, o grupo CAF foi distribuído em dois grupos: Grupo cafeteria submetido à falsa operação (CAF SHAM) e Grupo cafeteria submetido à DDJ (CAF DDJ). Após a cirurgia, ambos os grupos CAF continuaram a receber a dieta de cafeteria. Passadas oito semanas, os animais foram eutanasiados e amostras do músculo diafragma foram coletadas para análise das fibras musculares, quantificação de colágeno e avaliação morfométrica das JNMs. Os animais do grupo CAF SHAM apresentaram aumento do peso corporal, no índice de Lee e nas gorduras retroperitoneal e periepididial quando comparado ao grupo CTL e a cirurgia de DDJ não reverteu este parâmetro. A estrutura das fibras musculares e das JNMs foram semelhante entre os grupos CAF SHAM e CTL. No entanto, o grupo CAF SHAM apresentou alterações na ultraestrutura das fibras como miofibrilas frouxamente arranjadas e desorganização de linha Z no músculo diafragma. Além disso, o grupo CAF SHAM apresentou uma quantidade considerável de gotículas de lipídios e redução na porcentagem de colágeno quando comparado ao grupo CTL. A DDJ não afetou a estrutura e a ultraestrutura das fibras musculares ou das JNMs do músculo diafragma dos animais do grupo CAF DDJ. Dois meses após o procedimento, a DDJ não melhorou as alterações observadas no músculo diafragma de ratos obesos induzidos por dieta de cafeteria.

Made available in DSpace on 2017-07-10T14:17:16Z (GMT). No. of bitstreams: 1 Mariana Carla Mendes.pdf: 1848607 bytes, checksum: 083213cf0c0ad5bc3014210dd258c5e6 (MD5) Previous issue date: 2015-02-02 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study was designed to evaluate whether DJB in western diet (WD)-obese rats could have effects on pancreatic &#946;-cell morphology and islet responsiveness to potentiating agents involved with the protein kinase A (PKA) and C (PKC) pathway. Male Wistar rats with 8 weeks of life were fed a standard rodent chow diet (CTL group) or WD ad libitum. After 10 weeks, WD rats were submitted to sham operation or DJB, forming WD SHAM and WD DJB group, respectively. After two months, the obesity parameters, insulin resistance (IR), pancreas morphology, insulin secretion stimulate by different secretagogues and islet protein expression were verified. WD SHAM rats displayed obesity, hyperglycemia, hyperinsulinemia, glucose intolerance and IR. In addition, they also presented an increase in islets and &#946;-cells area and mass. The glucose-induced insulin secretion stimulated by 11.1 mM glucose in the presence of carbachol (CCh), PMA, Forskolin or IBMX was higher in WD SHAM islets than CTL islets. DJB surgery did not alter body weight but normalized glucose, insulinemia, IR, and decreased islet and &#946;-cells mass. The insulin release stimulated by glucose in the presence of CCh, PMA, Forskolin or IBMX was too normalized in WD DJB group. The expression of glucokinase, PKC, PKA and sintaxin was not altered in WD SHAM rats, but the M3 receptor was down-regulated. DJB did not influence these protein expressions. DJB surgery normalized glicemia, insulinemia and IR, reduced islets and &#946;-cell mass and normalized insulin secretion by PKC and PKA pathway. / O presente estudo avaliou o efeito da derivação duodeno jejunal (DDJ) em ratos obesos pela dieta de cafeteria (CAF) sobre a morfofisiologia, com enfâse na ação de agentes potencializadores da secreção de insulina. Ratos Wistar com 8 semanas de vida receberam dieta padrão formando o crupo controle (CTL) ou CAF ad libitum. Após 10 semanas, os ratos CAF foram submetidos à falsa operação ou a DDJ, formando os grupos CAF SHAM e CAF DDJ, respectivamente. Após dois meses, foram avaliados os parâmetros de obesidade, resistência à insulina (RI), morfologia do pâncreas, secreção de insulina estimulada por glicose, carbacol (CCh), PMA, IBMX e Forscolina, e a expressão proteica de glicoquinase (GCK), receptor muscarínico M3, proteina quinase C e A (PKC e PKA) e Sintaxina-1, nas ilhotas. Os animais do grupo CAF SHAM tornaram-se obesos, hiperglicêmicos, hiperinsulinêmicos, intolerantes à glicose e resistentes à insulina. Além disso, apresentaram aumento na massa da ilhota e das células &#946;. A secreção de insulina estimulada por 11.1 mM de glicose na presença de CCh, PMA, Forskolin ou IBMX foi significativamente maior no grupo CAF SHAM em relação ao grupo CTL. A DDJ não alterou o peso corporal, mas normalizou a glicemia, insulinemia, a RI e diminuiu a massa das ilhotas e das células &#946;. A secreção de insulina estimulada pelos diferentes secretagogos também foi normalizada no grupo CAF DDJ. A expressão proteica da GCK, PKC, PKA e sintaxina não foi alterada no grupo CAF SHAM em relação ao CTL, todavia a expressão do receptor M3 foi reduzida. A DDJ não influenciou na expressão dessas proteínas. Em conclusão, a cirurgia de DDJ normalizou a glicemia, a insulinemia e a RI, reduziu a massa das ilhotas e das células &#946; bem como, normalizou a secreção de insulina via PKC e PKA.