There are many tools available for the study of post-translational modifications. The majority of these tools is specific towards the individual modification and involves separation of modified proteins from non-modified ones. The drawback of using a modification specific method is that there is a lack of flexibility in its usage for other modifications. The goal of these studies was to investigate the possibility of obtaining a similar separation effect by fractionating post-translationally modified proteins based on the physical properties of proteins. The post-translational modification chosen to be the basis of this study was the O-GlcNAc modification. Using the C2C12 mouse myoblast cell line, it was determined that the optimal conditions for producing lysates containing increased yields of O-GlcNAc modified proteins was to treat differentiated C2C12 cells with 10nM insulin, 12g/L glucose and 2mM of the O-GlcNAcase inhibitor Streptozotocin for 24 hours. Using the optimized lysis buffer, it was shown that protein separation by surface charge using standard anion exchange separation did not provide enough resolution or material to obtain any identifications of modified proteins. However, when a chromatofocusing method which separates proteins on the basis of their isoelectric points was used, a separation scheme with larger capacity and higher resolution was possible. Using this separation method followed by gel electrophoresis of individual fractions, proteins which are potentially O-GlcNAc modified were identified by mass spectrometry. It was evident from the number of protein bands observed per fraction on the Coomassie stained gels and the number of proteins identified per protein band by mass spectrometry that further reduction in sample complexity was required to assist in the positive identification of O-GlcNAc modified proteins. Among the identified proteins, 32 percent were metabolic proteins, 21 percent were protein processing proteins, 16 percent were structural proteins and the remainder a mix of other proteins. Unfortunately, it was not possible to validate the presence or absence of the O-GlcNAc modification on these proteins using available methodologies such as immunoprecipitation. As such, further work is required to optimize the separation strategy and to verify the usefulness of this separation strategy in identifying O-GlcNAc/post-translationally modified proteins. / Medicine, Faculty of / Medicine, Department of / Experimental Medicine, Division of / Graduate

Alloxan (ALX) ist ein klassisches Diabetogen, welches in Nagetieren spezifisch pankreatische ß-Zellen zerstört und Symptome induziert, die dem humanen Typ-1-Diabetes vergleichbar sind. Durch eine einmalige, intravenöse (iv) Injektion einer subtoxischen Dosis von 50 mg ALX/kg Körpergewicht (KG) werden Schäden an der ß-Zelle hervorgerufen, die innerhalb von 48-72 Stunden in 50% der Mäuse einen Diabetes auslösen (Schwellenwert Euglykämie zu Hyperglykämie ist 11,1 mmol/l). Das toxische Potential von ALX besteht in der Generierung von reaktiven Sauerstoffspezies (ROS), vorwiegend Superoxidanion-, Wasserstoffperoxid- und Hydroxylradikalen. Ziel der vorliegenden Arbeit war zu untersuchen, ob durch ALX präferentiell Strukturen der ß-Zelle zerstört werden, die essentiell für die ß-Zellfunktion – die Insulinproduktion – sind. Diese sind u.a. der Glucosetransporter 2 (GLUT2), die Glucokinase und das Proinsulin. Daran anschliessend stellte sich die Frage, ob ALX-Toxizität durch Vorbehandlung mit D-Glucose (D-G), 5-Thio-D-Glucose (5-T-G) oder mit Zink-angereichertem Trinkwasser – zur Anreicherung des Antioxidants Metallothionein - verhindert werden kann. Hierzu wurden männliche C57BL/6- und 129S3-Mäuse entweder einmalig iv mit D-G oder 5-T-G vorbehandelt oder die Mäuse erhielten eine Woche vor der ALX-Injektion und über die gesamte Versuchsdauer hinweg Zink-angereichertes Trinkwasser. Anschliessend wurde der Einfluss auf den ALX-induzierten Diabetes, die orale Glucosetoleranz und die mRNA-Expression der oben genannten Gene mittels RT-PCR untersucht. Der Gesamtinsulingehalt der ALX-behandelten Pancreata wurde über die Bestimmung des immunreaktiven Insulins ermittelt. In der vorliegenden Arbeit wird gezeigt, dass 1.) die Vorbehandlung mit D-G den ALX-induzierten Diabetes signifikant (p0,001) verhinderte; 2.) trotz Euglykämie in mit D-G- und ALX-behandelten Mäusen eine pathologische orale Glucosetoleranz über Wochen als ALX-Folgeschaden persistierte; 3.) die Vorbehandlung mit 5-T-G, dem chemisch der D-G ähnlichsten Analog, jedoch den ALX-induzierten Diabetes signifikant (p0,001) potenzierte; 4.) Zink-angereichertes Trinkwasser die ALX-induzierte Hyperglykämie signifikant (p0,001) reduzierte; 5.) ALX zunächst die mRNA-Expression des GLUT2 signifikant (p0,001) reduzierte und nachfolgend auch signifikant (p0,05) die mRNA-Expression der Glucokinase, wenn auch weniger ausgeprägt als für die GLUT2-Expression; 6.) ALX keine Veränderung der mRNA-Expression von Proinsulin auslöste; 7.) die Vorbehandlung mit D-G signifikant (p0,05) die ALX-induzierte Reduktion der mRNA-Expression von GLUT2 und der Glucokinase verhinderte und 8.) der Insulingehalt im gesamten Pankreas 24 h nach ALX-Injektion signifikant (p0,05) reduziert wurde. Es wird geschlussfolgert, dass der GLUT2 und die Glucokinase primäre Zielstrukturen der ALX-Toxizität unter den verwendeten Versuchsbedingungen sind. Diese Läsionen sind die Ursache für den Diabetes. Durch Vorbehandlung mit D-G können der GLUT2 und die Glucokinase vor ALX-Toxizität geschützt werden, obwohl trotz Euglykämie unter physiologischen Bedingungen eine pathologische orale Glucosetoleranz als ALX-Folgeschaden in den Mäusen persistierte. Es muß noch geklärt werden, worin die Gründe für den protektiven Effekt der D-G und den potenzierenden Effekt der 5-T-G liegen und inwieweit ALX-induzierte Radikale selektiv wirksam sind, oder ob diese Selektivität auf anderen Mechanismen, wie z.B. Transkriptionsfaktoren, beruht. Letztendlich zeigen diese Befunde, dass sich der pathogenetische Mechanismus von ALX von anderen Diabetogenen unterscheidet, wie z.B. Streptozotozin, welches selektiv den GLUT2 schädigt, der durch Vorbehandlung mit 5-T-G vor der Streptozotocin-Toxizität geschützt werden kann. Daraus ist abzuleiten, dass es in der Präventivmedizin unterschiedlicher Vorsorgemassnahmen bedarf, um Risiko-patienten vor der Manifestation eines Diabetes mellitus zu schützen. / Type 1 diabetes results from irreversible damage of insulin-producing ß-cells. In laboratory animals, diabetes can be induced with alloxan (ALX). ALX is a potent generator of reactive oxygen species (ROS), which can mediate ß-cell toxicity. However, the initial lesions on essential ß-cell structures are not known. In this study, we analyzed the effect of ALX on the glucose transporter 2 (GLUT2), glucokinase and proinsulin. For this purpose, we investigated the effect of pretreatment with the glucose analogues D-glucose (D-G) and 5-thio-D-glucose (5-T-G), as well as with zinc-enriched drinking water to induce the antioxidant metallothionein, on ALX-induced diabetes, on oral glucose tolerance (OGT) and on the mRNA-expression of the above mentioned genes with semiquantitative RT-PCR in male C57BL/6 and 129S3 mice. The total insulin content of ALX-treated pancreata was determined as immune reactive insulin. One single intravenous (iv) injection of 50 mg ALX/kg body weight (bwt) induced diabetes in 50% of mice of both strains (blood glucose level 11.1 mmol/l). One single iv preinjection of D-G prevented significantly (p0,001) diabetes in both strains, yet, in these euglycemic mice, an impaired oral glucose tolerance persisted. In contrast, the pretreatment with a single injection of 5-T-G potentiated significantly (p0,001) the toxicity of ALX. Administration of zinc-enriched drinking water, however, reduced ALX-induced hyperglycemia (p0,001). The mRNA-expression of GLUT2 and glucokinase was time-dependently reduced and the effect was more pronounced for GLUT2 (p0,001) than for glucokinase (p0,05). The pretreatment with D-G protected against the mRNA-reduction of both GLUT2 and glucokinase (p0,05). Interestingly, the mRNA-expression of proinsulin remained unaffected as well as the pancreatic total insulin content. A significant (p0,05) reduction of pancreatic insulin content was found after 24 h. In conclusion, ALX exerts differential toxicity on essential ß-cell structures. This toxic effect was more pronounced for GLUT2 than for glucokinase mRNA. Pretreatment with D-G prevented ALX-toxicity, whereas in euglycemic mice an impaired oral glucose tolerance persisted. It has to be elucidated, whether ALX-induced ROS select essential ß-cell structures or whether, as one possibility, transcription factors in the ß-cell are specifically directing ROS to GLUT2 and glucokinase mRNA. Finally, these results differ from those obtained with other diabetogens, e.g., streptozotocin, which exerts selective toxicity on the GLUT2 and which is prevented by 5-T-G. However, diabetogens damage ß-cell function through different pathogenic pathways and, therefore, different interventional regimen may be required to prevent type 1 diabetes in individuals at risk.

Blood sugar levels were determined in toadfish and catfish by the Folin reducing procedure and a specific enzymatic glucose procedure. The difference between the two values was considered to be the rest reduction (RR). After alloxan injection, the RR level increased greatly reaching a peak at one hour and then decreasing. The glucose level rose more slowly. An attempt was made to study these changes in blood by paper chromatography using silver nitrate to detect reducing compounds. In normal blood, glucose, an unidentified compound, and several other reducing compounds present in small amounts were separated. The large amount or RR present after alloxan could not be detected by silver nitrate. The significance of the results was discussed and future investigations were suggested. / Thesis / Master of Science (MSc)

O diabetes mellitus (DM) é uma doença com prevalência e morbidade elevadas em todo o mundo, sendo que o DM1 é responsável por 5-10% dos casos. A vitamina D, hormônio de ação pleiotrópica, pode melhorar o curso do DM1, embora os mecanismos não estejam completamente elucidados. Dessa forma, ampliar o conhecimento sobre a ação desse hormônio pode auxiliar no prognóstico, bem como na compreensão dos possíveis mecanismos envolvidos na prevenção do DM. Neste trabalho, foram avaliados os efeitos fisiológicos da suplementação de vitamina D (800 UI/dia/sete dias; via oral) em camundongos machos (n=31; linhagem C57BL/6) distribuídos em quatro grupos: Controle + Água (CA; n=9); Controle + Vitamina D (CV; n=9); Diabético + Água (DA; n=6) e Diabético + Vitamina D (DV; n=7). Os camundongos tornados diabéticos (aloxana, 60 mg/Kg, intravenosa), quando comparados aos controles, exibiram redução do peso corporal e concentrações plasmáticas de glicose mais elevadas durante o período experimental de 10 dias (características do estado insulinopênico). Entretanto, a suplementação com vitamina D não alterou essa condição. Camundongos tornados diabéticos, em relação aos controles, exibiram redução do peso corporal (p<0,05) e concentrações plasmáticas de glicose (p<0,001) mais elevadas durante o período experimental. Animais suplementados com vitamina D apresentaram, em relação aos controles, níveis de 25(OH)D mais elevados (CA vs CV, p<0,001; DA vs DV, p<0,001). Níveis séricos maiores de ureia (CA vs DA, p<0,05; CA vs DV, p<0,01; CV vs DA, p<0,05; CV vs DV, p<0,01) e creatinina (CA vs DA, p<0,001; CA vs DV, p<0,001; CV vs DA, p<0,001; CV vs DV, p<0,001), espessamento da cápsula de Bowman, hipertrofia glomerular e destruição de hepatócitos foram observados em camundongos diabéticos em relação aos controles. Entretanto, a suplementação com vitamina D não alterou estas condições. O grupo DA apresentou menor nível sérico de albumina em relação aos grupos CA (p<0,05) e CV (p<0,05); níveis inferiores de hemoglobina (p<0,05) e hematócrito (p<0,05) em relação ao grupo DV; e menor leucometria (p<0,05) e mononucleares sanguíneos (p<0,05) em relação ao grupo CA. Os resultados sugerem que a vitamina D possa influenciar a resposta imunológica em animais diabéticos, modulando hematócrito, hemoglobina, bem como os níveis séricos de albumina / Diabetes mellitus (DM) is a disease with high prevalence and morbidity worldwide, and the DM1 is responsible for 5-10% of cases. The vitamin D hormone pleiotropic action, can improve the course of T1DM, although the mechanisms are not fully elucidated. Thus, better understanding the action of this hormone can aid in prognosis as well as in understanding the possible mechanisms involved in the prevention of diabetes. We evaluated the physiological effects of vitamin D (800 IU/day/seven days, v.o.) in male mice (n=31, C57BL/6 strain) divided into four groups: Control + Water (CW, n=9); Control Vitamin D + (CV n=9); Diabetic + Water (DW, n=6) Diabetic + Vitamin D (VD, n=7). The mice induced-diabetes by alloxan (60 mg/kg, i.v.), when compared to controls, exhibited reduced body weight and plasma glucose concentrations were higher during the experimental period of 10 days (features insulinopenic state). However, vitamin D supplementation did not alter this condition. Diabetic mice, compared to controls, exhibited reduced body weight (p<0,05) and plasma glucose concentrations (p <0.001) higher during the trial period. Animals supplemented with vitamin D showed higher levels of 25 (OH) D than controls (CW vs CV, p <0,001; DW vs DV, p<0,001). Higher serum urea (CW vs. DW, p <0,05; CW vs DV, p <0,01; CV vs DA, p <0,05; CV vs DV, p <0,01) and creatinine (CW vs. DW, p <0,001; CW vs DV, p <0,001; CV vs DW, p <0,001; CV vs DW, p <0,001), thickening of Bowman\'s capsule, glomerular hypertrophy and destruction of hepatocytes were observed in diabetic mice compared to controls. However, vitamin D supplementation did not alter these conditions. The DW group showed lower serum albumin compared to CW (p<0,05) and CV (p<0,05) groups; lower hemoglobin (p<0,05) and hematocrit (p <0,05) compared to the DV group; and lower leukocyte counts compared to CW (p <0,05) and mononuclear blood (p <0,05) compared to the CW group. The results suggest that Vitamin D may influence the immune response in diabetic animals, modulating hematocrit, hemoglobin and serum albumin

Diabetes mellitus is associated with several clinically significant abnormalities in the oral cavity and salivary glands, the most common being periodontitis, salivary gland enlargement and a sensation of dry mouth. The pre­valence of dental caries in diabetics is mostly reported to be decreased or unaffected. Since there is a shortage of information concerning the influence of metabolic control and duration of diabetes on these abnormalities, the present studies were performed. Three-month-old rats were made alloxan-diabetic and investigated after one and twelve months’ duration of dia­betes for oral lesions and feeding behavior. They had free access to a standard pellet diet and tap water. Strepto­coccus mutans and lactobacilli were naturally occurring. In diabetic rats the proportion of the oral flora which was lactobacilli was positively correlated to the blood glucose level. Untreated long-term alloxan-diabetic rats de­veloped advanced periodontal disease and root surface caries in the molars at sites of interdental impaction of foreign material. The degree of alveolar bone loss was positively correlated to the blood glucose level. Diabetic rats were hyperphagic and had a longer total eating time, including day-time eating, mainly by having longer meals but no significant increase of meal frequency, as compared with non-diabetic animals. The untreated al­loxan-diabetic rats developed reduced salivary gland weight which was of the same degree in short- and long­term diabetic animals. Short- and long-term untreated alloxan-diabetic rats showed a similar degree of morpho- metrically estimated lipid accumulation in the acinar cells of the submandibular glands, and the degree was posi­tively correlated to the blood glucose level. However, lipid inclusion occurred only in rats with a morning non­fasting blood glucose level exceeding 15 mmol/L. The capillaries in the submandibular glands of the untreated long-term alloxan-diabetic rats had a significantly increased thickness of the basement membranes as compared with the observations in short-term diabetic and non-diabetic rats. Untreated alloxan-diabetic rats were also shown to have a decreased salivary flow rate compared with non-diabetic rats, and the decreased flow was negatively correlated to the blood glucose concentration. Salivary flow rate increased with the duration of the disease. The diabetic rats had increased salivary glucose levels, which were positively correlated to blood glucose values when the latter were above 15 mmol/L, suggesting a threshold mechanism for salivary glucose excretion. Insulin therapy reversed salivary flow rate and salivary glucose concentrations toward normal. Salivary investigations were performed in eleven diabetic patients on two occasions with different metabolic con­trol. Salivary flow rate showed marked interindividual differences but was not significantly changed by improv­ed metabolic control although several of the patients initially had severely deranged glucose metabolism. A posi­tive correlation between the glucose concentration in blood and saliva was seen in the parotid saliva during secre­tory stimulation. No significant change in electrolytes, amylase or antimicrobial factors was found. / <p>S. 1-48: sammanfattning, s. 49-90: 5 uppsatser</p> / digitalisering@umu

The hyperglycemia and oxidative stress are factors strongly involved on development of many disorders that characterize the Diabetes Mellitus. It is known that some organic and inorganic selenium compounds are potent antioxidant agents and present similar activity to the insulin in the control of hyperglycemia. Base on these data, the present study evaluated the effect of the organoselenium compound, diphenyl diselenide, on the δ-ALA-D activity and biochemical parameters of diabetic type 1 rats, induced by alloxan. The animals were treated with 6 consecutives doses of diphenyl diselenide (10 mg/kg, s.c) administrated before (pretreatment) or after (post-treatment) diabetes induction. Diphenyl diselenide presented inhibitory effect per se on hepatic and renal δ-ALA-D activity. However, this effect was not verified on other tissues. Regarding aminotransaminases, there was no difference on aminotransaminases for both diphenyl diselenide pre and post treated rats at the first week of the induction. Besides, the results suggest that diphenyl diselenide seem to possess ability to regulate the levels of plasma glucose and serum fructosamine altered in diabetic animals. Thus, diphenyl diselenide was not effective in protecting δ-ALA-D inhibition verified in this dose and protocol. However, this compound seems to possess hepatic protector effect and property of reducing the hyperglycemia. Considering that diphenyl diselenide has a simple chemistry structure and it is easily prepared, new studies could be carried out to investigate other pharmacological properties as well the mechanisms involved in diphenyl diselenide effects. / A hiperglicemia e o estresse oxidativo são fatores fortemente envolvidos no desenvolvimento de muitos distúrbios que caracterizam o Diabetes Mellitus. Sabe-se que alguns compostos orgânicos e inorgânicos de selênio são potentes agentes antioxidantes e que determinados compostos inorgânicos de selênio apresentam atividade similar à insulina no controle da hiperglicemia. Baseando-se nesses dados, o presente estudo avaliou o efeito do composto orgânico de selênio, disseleneto de difenila, na atividade da enzima δ-ALA-D e em parâmetros bioquímicos de ratos diabéticos tipo 1, induzidos com aloxano. Os animais foram tratados com 6 doses consecutivas de disseleneto de difenila (10 mg/kg, s.c) administrado antes (pré-tratamento) ou após (pós-tratamento) à indução de Diabetes. O composto em questão apresentou atividade inibitória per se sobre a atividade da enzima δ-ALA-D hepática e renal dos animais pré e pós-tratados e sacrificados 14 dias após a indução. Em contrapartida não foi verificado efeito sobre os demais tecidos. Sobre a atividade hepática, o disseleneto de difenila manteve os níveis de aminotransferases comparáveis aos níveis do controle apenas na primeira semana da indução, tanto no pré quanto no pós-tratamento. Além disso, os resultados encontrados sugerem que o disseleneto de difenila parece possuir a habilidade de regular os níveis de glicose sanguínea e frutosamina sérica que estavam alteradas nos animais diabéticos. Desta maneira, o disseleneto de difenila não foi eficaz em proteger a inibição da atividade da enzima δ-ALA-D verificada nesta dose e protocolo testados, entretanto ele parece possuir atividade hepatoprotetora e propriedade redutora do estado de hiperglicemia. Assim novos estudos poderiam ser realizados para investigar outras propriedades do disseleneto de difenila e os mecanismos envolvidos nestes efeitos farmacológicos, levando também em consideração que o mesmo possui uma estrutura química relativamente simples, que de fato representaria uma vantagem econômica.

O diabetes mellitus (DM) é uma doença com prevalência e morbidade elevadas em todo o mundo, sendo que o DM1 é responsável por 5-10% dos casos. A vitamina D, hormônio de ação pleiotrópica, pode melhorar o curso do DM1, embora os mecanismos não estejam completamente elucidados. Dessa forma, ampliar o conhecimento sobre a ação desse hormônio pode auxiliar no prognóstico, bem como na compreensão dos possíveis mecanismos envolvidos na prevenção do DM. Neste trabalho, foram avaliados os efeitos fisiológicos da suplementação de vitamina D (800 UI/dia/sete dias; via oral) em camundongos machos (n=31; linhagem C57BL/6) distribuídos em quatro grupos: Controle + Água (CA; n=9); Controle + Vitamina D (CV; n=9); Diabético + Água (DA; n=6) e Diabético + Vitamina D (DV; n=7). Os camundongos tornados diabéticos (aloxana, 60 mg/Kg, intravenosa), quando comparados aos controles, exibiram redução do peso corporal e concentrações plasmáticas de glicose mais elevadas durante o período experimental de 10 dias (características do estado insulinopênico). Entretanto, a suplementação com vitamina D não alterou essa condição. Camundongos tornados diabéticos, em relação aos controles, exibiram redução do peso corporal (p<0,05) e concentrações plasmáticas de glicose (p<0,001) mais elevadas durante o período experimental. Animais suplementados com vitamina D apresentaram, em relação aos controles, níveis de 25(OH)D mais elevados (CA vs CV, p<0,001; DA vs DV, p<0,001). Níveis séricos maiores de ureia (CA vs DA, p<0,05; CA vs DV, p<0,01; CV vs DA, p<0,05; CV vs DV, p<0,01) e creatinina (CA vs DA, p<0,001; CA vs DV, p<0,001; CV vs DA, p<0,001; CV vs DV, p<0,001), espessamento da cápsula de Bowman, hipertrofia glomerular e destruição de hepatócitos foram observados em camundongos diabéticos em relação aos controles. Entretanto, a suplementação com vitamina D não alterou estas condições. O grupo DA apresentou menor nível sérico de albumina em relação aos grupos CA (p<0,05) e CV (p<0,05); níveis inferiores de hemoglobina (p<0,05) e hematócrito (p<0,05) em relação ao grupo DV; e menor leucometria (p<0,05) e mononucleares sanguíneos (p<0,05) em relação ao grupo CA. Os resultados sugerem que a vitamina D possa influenciar a resposta imunológica em animais diabéticos, modulando hematócrito, hemoglobina, bem como os níveis séricos de albumina / Diabetes mellitus (DM) is a disease with high prevalence and morbidity worldwide, and the DM1 is responsible for 5-10% of cases. The vitamin D hormone pleiotropic action, can improve the course of T1DM, although the mechanisms are not fully elucidated. Thus, better understanding the action of this hormone can aid in prognosis as well as in understanding the possible mechanisms involved in the prevention of diabetes. We evaluated the physiological effects of vitamin D (800 IU/day/seven days, v.o.) in male mice (n=31, C57BL/6 strain) divided into four groups: Control + Water (CW, n=9); Control Vitamin D + (CV n=9); Diabetic + Water (DW, n=6) Diabetic + Vitamin D (VD, n=7). The mice induced-diabetes by alloxan (60 mg/kg, i.v.), when compared to controls, exhibited reduced body weight and plasma glucose concentrations were higher during the experimental period of 10 days (features insulinopenic state). However, vitamin D supplementation did not alter this condition. Diabetic mice, compared to controls, exhibited reduced body weight (p<0,05) and plasma glucose concentrations (p <0.001) higher during the trial period. Animals supplemented with vitamin D showed higher levels of 25 (OH) D than controls (CW vs CV, p <0,001; DW vs DV, p<0,001). Higher serum urea (CW vs. DW, p <0,05; CW vs DV, p <0,01; CV vs DA, p <0,05; CV vs DV, p <0,01) and creatinine (CW vs. DW, p <0,001; CW vs DV, p <0,001; CV vs DW, p <0,001; CV vs DW, p <0,001), thickening of Bowman\'s capsule, glomerular hypertrophy and destruction of hepatocytes were observed in diabetic mice compared to controls. However, vitamin D supplementation did not alter these conditions. The DW group showed lower serum albumin compared to CW (p<0,05) and CV (p<0,05) groups; lower hemoglobin (p<0,05) and hematocrit (p <0,05) compared to the DV group; and lower leukocyte counts compared to CW (p <0,05) and mononuclear blood (p <0,05) compared to the CW group. The results suggest that Vitamin D may influence the immune response in diabetic animals, modulating hematocrit, hemoglobin and serum albumin

Made available in DSpace on 2016-01-26T18:55:31Z (GMT). No. of bitstreams: 1 Dissertao_Final[1].pdf: 848491 bytes, checksum: 6fe1a8632b97df927b7abf789ceb1fc5 (MD5) Previous issue date: 2011-06-27 / This study was to compare the effects the action diabetogenic of alloxan in different doses, through its administration intraperitoneally (ip) in Wistar rats. The animals were distributed randomly four in experimental groups: experimental control group (GC), consisting of 30 rats subjected to injection (ip) of sodium chloride solution 0.9%; Group 1 (G1), 2 (G2) and 3 (G3) consisting of 60 rats each, subject to injection (ip) alloxan 2% at doses of 120, 150 and 200 mg/kg, respectively. Were evaluated during 15 days, on the following parameters: blood glucose, weight, water intake, dietary intake, urination chemical examination of urine (glucose, ketone bodies, and other parameters). It was concluded that the dose of 120 mg/kg alloxan at 2% (ip), when compared to the doses was most efficient, compared to the objectives of this study, it induced diabetes in a larger number of animals and promoted a low percentage of deaths. / Este estudo teve por objetivo comparar os efeitos da ação diabetogênica da aloxana em diferentes doses, por meio da sua administração intraperitoneal (ip) em ratos Wistar. Os animais foram distribuídos, aleatoriamente, em quatro grupos experimentais: grupo controle (GC), constituído por 30 ratos submetidos à injeção (ip) de solução de cloreto de sódio 0,9%; grupo 1 (G1), 2 (G2) e 3 (G3) constituídos por 60 ratos cada, submetidos à injeção (ip) de aloxana 2% nas doses de 120, 150 e 200mg/kg, respectivamente. Foram avaliados durante 15 dias, quanto aos seguintes parâmetros: glicose sanguínea, peso, ingestão hídrica, ingestão alimentar, volume urinário, exame químico da urina (glicose, corpos cetônicos e outros parâmetros). Concluiu-se que, a dose de 120mg/kg de aloxana a 2% (ip), quando comparada às demais doses foi a mais eficiente, frente aos objetivos deste estudo, pois induziu o diabetes em um maior número de animais e promoveu um baixo percentual de óbitos.

Made available in DSpace on 2016-01-26T18:55:35Z (GMT). No. of bitstreams: 1 Gloriane.pdf: 339722 bytes, checksum: 49acd72d8b81935d6eac075d17d943ac (MD5) Previous issue date: 2012-09-26 / The aim of this study was to monitor the induction of experimental diabetes mellitus in female Wistar rats by intraperitoneal administration of alloxan in different doses and dose to assess which provides the highest incidence of diabetes with lower death rates. Four experimental groups of 30 animals each as follows: control group (CG) received intraperitoneal (ip) solution of sodium chloride 0.9% and group G80, G120 and G200, received via (ip) diluted in 2% alloxan solution physiological doses of 80, 120 and 200mg/kg respectively. We evaluated blood glucose, temperature, weight, water intake, food intake and percentage of deaths at different times. It is concluded that all doses of alloxan administered intraperitoneally after 24 hours of fasting were able to induce diabetes mellitus and monitoring of temperature, glucose and dehydration of the animals during the first week, was paramount to the success of induction, and 120mg/kg dose of the most effective in achieving greater number of diabetic animals and lower incidence of deaths. / O objetivo deste trabalho foi monitorar a indução experimental do diabetes mellitus em ratos Wistar fêmeas, pela administração intraperitoneal de aloxana em diferentes doses e avaliar qual dose estabelece a maior incidência de diabetes com menor índice de óbitos. Quatro grupos experimentais com 30 animais em cada um sendo: grupo controle (GC) recebeu via intraperitoneal (ip) solução de cloreto de sódio 0,9%; grupo G80, G120 e G200, receberam via (ip) aloxana 2% diluída em solução fisiológica nas doses de 80, 120 e 200mg/Kg respectivamente. Avaliou-se glicemia, temperatura, peso, ingestão hídrica, ingestão alimentar e percentual de óbitos em diferentes momentos. Conclui-se que todas as doses de aloxana administrada pela via intraperitoneal após 24 horas de jejum foram capazes de induzir o diabetes mellitus e o monitoramento da temperatura, glicemia e desidratação dos animais na primeira semana, foi de suma importância para o sucesso da indução, sendo a dose de 120mg/Kg a mais eficaz para obtenção de maior número de animais diabéticos e menor incidência de óbitos.

Made available in DSpace on 2016-07-18T17:53:08Z (GMT). No. of bitstreams: 1 Dissertao_Final[1].pdf: 848491 bytes, checksum: 6fe1a8632b97df927b7abf789ceb1fc5 (MD5) Previous issue date: 2011-06-27 / This study was to compare the effects the action diabetogenic of alloxan in different doses, through its administration intraperitoneally (ip) in Wistar rats. The animals were distributed randomly four in experimental groups: experimental control group (GC), consisting of 30 rats subjected to injection (ip) of sodium chloride solution 0.9%; Group 1 (G1), 2 (G2) and 3 (G3) consisting of 60 rats each, subject to injection (ip) alloxan 2% at doses of 120, 150 and 200 mg/kg, respectively. Were evaluated during 15 days, on the following parameters: blood glucose, weight, water intake, dietary intake, urination chemical examination of urine (glucose, ketone bodies, and other parameters). It was concluded that the dose of 120 mg/kg alloxan at 2% (ip), when compared to the doses was most efficient, compared to the objectives of this study, it induced diabetes in a larger number of animals and promoted a low percentage of deaths. / Este estudo teve por objetivo comparar os efeitos da ação diabetogênica da aloxana em diferentes doses, por meio da sua administração intraperitoneal (ip) em ratos Wistar. Os animais foram distribuídos, aleatoriamente, em quatro grupos experimentais: grupo controle (GC), constituído por 30 ratos submetidos à injeção (ip) de solução de cloreto de sódio 0,9%; grupo 1 (G1), 2 (G2) e 3 (G3) constituídos por 60 ratos cada, submetidos à injeção (ip) de aloxana 2% nas doses de 120, 150 e 200mg/kg, respectivamente. Foram avaliados durante 15 dias, quanto aos seguintes parâmetros: glicose sanguínea, peso, ingestão hídrica, ingestão alimentar, volume urinário, exame químico da urina (glicose, corpos cetônicos e outros parâmetros). Concluiu-se que, a dose de 120mg/kg de aloxana a 2% (ip), quando comparada às demais doses foi a mais eficiente, frente aos objetivos deste estudo, pois induziu o diabetes em um maior número de animais e promoveu um baixo percentual de óbitos.