Experimental model of nephropathy associated with diabetes mellitus in mice

Purpose: Nontransmissible chronic diseases, such as diabetes mellitus (DM) and nephropathy, affect a significant portion of the population, often treated due to injuries that require healing and regeneration. To create an experimental model of associated comorbidities, for healing and regeneration studies, protocols for induction of nephropathy by ischemia and reperfusion (I/R) and induction of DM by injection of streptozotocin (STZ) were associated. Methods: Sixty-four mice (Mus musculus), female, adult, Swiss strain, weighing approximately 20 g, were divided into four groups: G1: control (n = 24), G2: nephropathy group (N) (n = 7), G3, DM (n = 9), and G4: N+DM (n = 24). Arteriovenous stenosis (I/R) of the left kidney was performed as the first protocol. The animals received a hyperlipidemic diet for 7 days after the injection of STZ (150 mg/kg, via i.p.) and an aqueous glucose solution (10%) for 24 h. The animals in the G3 and G4 groups were observed for 14 days before receiving the diet and STZ. The evolution of nephropathy was observed using a urine test strip and the DM, through the analysis of blood glucose with a reagent strip on a digital monitor. Results: The ischemic induction protocols of nephropathy and DM with STZ, associated, were sustainable, low-cost, and without deaths. There were alterations compatible with initial renal alterations, in the first 14 days, such as increased urinary density, pH alteration, presence of glucose, proteins and leukocytes, when compared to the control group. DM was confirmed by the presence of hyperglycemia 7 days after induction and its evolution after 14 days. The animals in the G4 group showed constant weight loss when compared to the other groups. It was possible to observe morphological alterations in the kidneys submitted to I/R, regarding coloration, during surgery and after the end of the observation period, in the volume and size of the left kidney, when compared to the contralateral kidney. Conclusion: It was possible to induce nephropathy and DM associated in the same animal, in a simple way, confirmed with rapid tests, without losses, providing a basis for future studies.

Analysis of high-intensity interval training on bone mineral density in an experimental model of type 2 diabetes

Purpose: To analyze the effect of high-intensity interval training (HIIT) on bone mineral density (BMD) in a model of type 2 diabetes mellitus. Methods: Thirty-two male, adult, 12-week-old rats (Rattus norvegicus), of the Wistar lineage, were used. The animals induced to the experimental model received a high fat diet for 10 days and, after that period, intraperitoneal injection of streptozotocin (40 mg·kg­1), dissolved in 20 mmol·L­1 sodium citrate solution (pH = 4.5). The experimental group of diabetes was formed by the animals that, 48 h after the injection of streptozotocin, had fasting blood glucose > 250 mg·dL­1). The animals were randomly divided into four groups with eight animals each: HIIT experimental diabetes; HIIT control; sedentary experimental diabetes and sedentary control. The animals in the HIIT group performed an aerobic exercise protocol on a treadmill inclined at an angle of 15° to the horizontal, with interspersed intensity. Five weekly sessions, lasting 49 min each, were held for 6 weeks. The analysis of cortical bone density (CBD) and BMD were performed by X-ray images using the In-Vivo Xtreme II/Bruker system. Results: For CBD and BMD, when comparing diabetes and control groups, a significant difference was seen between groups in relation to HIIT (p = 0.007). Animals submitted and not submitted to HIIT in the same group showed a significant difference between groups in relation to diabetes (p < 0.001). Conclusions: The HIIT experimental diabetes group had increased CBD and BMD in comparison with the sedentary experimental diabetes group.

A non-inferiority study to compare daily fast-acting insulin versus twice a week slow-acting insulin moderate diabetes mode

Purpose Given the high prevalence of diabetes (D), several animal models have been analyzed. In the literature, most of the animal models have studied severe D. However, in clinical practice, most patients have moderate disease. Therefore, the present study aimed to describe a moderate D condition. Methods We analyzed 20 Wistar rats, age eight-weeks, weight between 200g-250g. All animals received an intravenous injection of Streptozotocin (55mg/kg weight). On the 15th day after D induction, the animals were divided into two groups: Group I animals receiving a single daily dose of fast-acting insulin (FAIG) NPH (1UI,SC) for partial glycemic control, and Group II - animals receiving slow-acting insulin (SAIG) twice a week. We measured glycemia, weight, and adverse events every week during two months. Results Of the total of animals analyzed in the study, three animals died in the FAIG and two animals died in the SAIG. Regarding the glycemic level, results were 339.5 ± 125.4mg/dL (95CI 302.3402 to 376.6842) in the FAIG, and 367.8 ± 66.1mg/dL (95IC 333.7607 to 401.8978) in the SAIG. There was no difference between groups as to weight during the study. Conclusion The use of slow-acting-insulin is not inferior to the use of fast-acting-insulin in the management of partially insulin-controlled moderate diabetes in rats.(AU)

Ginsenoside Rb1 attenuates diabetic retinopathy in streptozotocin-induced diabetic rats

Purpose:To investigated the effects of ginsenoside Rb1 on diabetic retinopathy in streptozotocin-induced diabetic rats.Methods:Diabetes was induced by a single intraperitoneal injection of streptozotocin (80 mg/kg) in male Wistar rats. Ginsenoside Rb1 (20, 40 mg/kg) was injected (i.p.) once a day for 4 weeks. Then, using fundus photography, the diameter and vascular permeability of retinal vessels were investigated. Retinal histopathology was undertaken. Contents of malondialdehyde (MDA) and glutathione (GSH) in retinas were assayed. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione cysteine ligase catalytic subunit (GCLC), and glutathione cysteine ligase modulatory subunit (GCLM) were measured.Results:Treatment with ginsenoside Rb1 attenuated the diabetes-induced increase in the diameter of retinal blood vessels. Ginsenoside Rb1 reduced extravasation of Evans Blue dye from retinal blood vessels. Ginsenoside Rb1 partially inhibited the increase in MDA content and decrease in GSH level in rat retinas. Nrf2 levels in the nuclei of retinal cells and expression of GCLC and GCLM were increased significantly in rats treated with ginsenoside Rb1.Conclusion:These findings suggest that ginsenoside Rb1 can attenuate diabetic retinopathy by regulating the antioxidative function in rat retinas.(AU)

Impact of 1, 25(OH) 2 D 3 on TG content in liver of rats with type 2 diabetes

Purpose: To evaluate the effects of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) on the content of triglyceride (TG), as well as on the gene and protein expressions of adiponectin receptor 2 (AdipoR2), p38 mitogen-activated protein kinase (P38MAPK), and lipoprotein lipase (LPL) in the liver of rats with type 2 diabetes mellitus (T2DM) so as to provide theoretical basis for exploring the mechanism by which 1,25(OH)2D3 regulates TG. Methods: Wistar rats were divided into four groups (n=25), with different treatments and detected the gene and protein expressions of AdipoR2, p38MAPK, and LPL in the liver tissue by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Meanwhile, the content of TG in the liver tissue was detected by the Enzyme-linked immunosorbent assay. Results: The expression of AdipoR2, p38MAPK, LPL gene and protein in the liver of VitD intervention group was significantly higher than that in T2DM group (P<0.05), while the TG content was significantly lower than that in T2DM group (P<0.05). Conclusion: 1,25(OH)2D3 can decrease the content of TG in the liver, and its mechanism may be achieved by upregulating the expressions of AdipoR2, p38MAPK, and LPL in the liver.(AU)

Effect of melatonin on antioxidant capacity, inflammation and apoptotic cell death in lung tissue of diabetic rats

Purpose: To investigate the effects of melatonin on antioxidant capacity, inflammation and apoptotic cell death (through expression of cleaved-caspase 3) in lung tissue samples of diabetic rats. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group) was made up of healthy rats. Group 2 (diabetes group) received streptozotocin at a dose of 50 mg/kg/day for 5 days.Group 3 (diabetes plus melatonin group) received streptozotocin at a dose of 50 mg/kg/day for 5 days and then they received melatonin at a dose of 20 mg/kg/day between 28th and 35th days of the study. Results: Tissue MDA and MPO levels were found to be significantly higher in diabetes group compared to control group (p< 0.05) whilst administration of melatonin was found to significantly lower this increase down to normal levels (p <0.05). Bronchus associated lymphoid tissue (BALT) was more severe in diabetics whereas administration of melatonin alleviated this hyperplasia. Cleaved caspase 3 activity was severe in hyperplastic BALT in diabetic rats however in lowered down to moderate level when melatonin was administered. Conclusion: The melatonin caused an increase in antioxidant capacity and decreased the expression of cleaved-caspase 3.(AU)

Protocolos perinatais empregados para a avaliação do diabetes mellitus gestacional induzido por estreptozotocina em ratas / Perinatal protocols employed for the evaluation of diabetes mellitus gestational induced by streptozotocin in rats

Muitos protocolos experimentais pré-clinicos in vivo empregam a estreptozotocina (STZ) como ferramenta farmacológica para a compreensão das sequelas que acometem os indivíduos expostos à hiperglicemia gestacional. O objetivo deste estudo foi sintetizar os diversos protocolos experimentais utilizados para os estudos de embriões, fetos e filhotes de ratas com diabetes mellitus gestacional (DMG) induzida por estreptozotocina (DMG-STZ). Realizou-se uma revisão integrativa da literatura sobre as abordagens metodológicas aplicadas aos estudos da DMG-STZ em ratos. Três pontos foram destacados nesta revisão: a) Doses e principais vias de administração da STZ, concentração plasmática de glicose para reconhecimento do DMG-STZ; b) Protocolos empregados para a avaliação pré-natal; c) Protocolos empregados para a avaliação do desenvolvimento pós-natal. As doses encontradas nos protocolos variaram entre 30 e 135 mg/Kg para administração por via intraperitoneal; entre 15 e 65 mg/Kg para via intravenosa e na dose de 45 mg/Kg para via subcutânea. Os valores glicêmicos sanguíneos para reconhecimento do DMG ficaram entre 97 e 500 mg/dL. Os estudos pré-natais abordaram a embriopatia diabética associada ao desenvolvimento do sistema nervoso central e à função renal, além das alterações do transporte útero- -placentário-fetal; os estudos pós-natais enfatizaram a correlação entre a macrossomia neonatal e a dislipidemia pós-natal, o desenvolvimento comportamental pós-natal e as alterações cardiovasculares. Embora existam grandes diferenças metodológicas entre os protocolos empregados, podemos concluir que a DMG-STZ ainda é um bom modelo para os estudos dos efeitos da hiperglicemia sobre os conceptos.

Many in vivo preclinical experimental protocols employ streptozotocin (STZ) as a pharmacological tool for understanding sequelae affecting individuals exposed to gestational hyperglycemia. The objective of this study was to synthesize the different experimental protocols that have been used to examine the embryos, fetuses, and pups of rats with Gestational Diabetes Mellitus (GDM) induced by streptozotocin (GDM-STZ). In this work, we have developed an integrative literature review, including quantitative methodological approaches that can be applied to studies of GDM-STZ in rats. Three points were highlighted in this study: a) Doses and central routes of STZ administration, and plasma glucose concentration for recognition of GDM-STZ; B) Protocols used for prenatal evaluation; c) Protocols used for the assessment of postnatal development. The doses ranged from 30 to 135 mg/kg for intraperitoneal administration; Between 20 and 65 mg/kg for the intravenous route and 45 mg/kg for the subcutaneous route. The blood glucose values for recognition of GDM were between 97 and 500 mg/dL. Prenatal studies approached diabetic embryopathy associated with central nervous system development and renal function in addition to changes in utero-placental-fetal transport. On the other hand, postnatal studies emphasized the correlation between neonatal macrossomia and postnatal dyslipidemia, postnatal behavioral development and cardiovascular changes. Although there are large methodological differences between the protocols employed, we can conclude from this review that GDM-STZ is still a good model for the studies of the effects of hyperglycemia on the concepts.

Protocolos perinatais empregados para a avaliação do diabetes mellitus gestacional induzido por estreptozotocina em ratas / Perinatal protocols employed for the evaluation of diabetes mellitus gestational induced by streptozotocin in rats

Muitos protocolos experimentais pré-clinicos in vivo empregam a estreptozotocina (STZ) como ferramenta farmacológica para a compreensão das sequelas que acometem os indivíduos expostos à hiperglicemia gestacional. O objetivo deste estudo foi sintetizar os diversos protocolos experimentais utilizados para os estudos de embriões, fetos e filhotes de ratas com diabetes mellitus gestacional (DMG) induzida por estreptozotocina (DMG-STZ). Realizou-se uma revisão integrativa da literatura sobre as abordagens metodológicas aplicadas aos estudos da DMG-STZ em ratos. Três pontos foram destacados nesta revisão: a) Doses e principais vias de administração da STZ, concentração plasmática de glicose para reconhecimento do DMG-STZ; b) Protocolos empregados para a avaliação pré-natal; c) Protocolos empregados para a avaliação do desenvolvimento pós-natal. As doses encontradas nos protocolos variaram entre 30 e 135 mg/Kg para administração por via intraperitoneal; entre 15 e 65 mg/Kg para via intravenosa e na dose de 45 mg/Kg para via subcutânea. Os valores glicêmicos sanguíneos para reconhecimento do DMG ficaram entre 97 e 500 mg/dL. Os estudos pré-natais abordaram a embriopatia diabética associada ao desenvolvimento do sistema nervoso central e à função renal, além das alterações do transporte útero- -placentário-fetal; os estudos pós-natais enfatizaram a correlação entre a macrossomia neonatal e a dislipidemia pós-natal, o desenvolvimento comportamental pós-natal e as alterações cardiovasculares. Embora existam grandes diferenças metodológicas entre os protocolos empregados, podemos concluir que a DMG-STZ ainda é um bom modelo para os estudos dos efeitos da hiperglicemia sobre os conceptos.(AU)

Many in vivo preclinical experimental protocols employ streptozotocin (STZ) as a pharmacological tool for understanding sequelae affecting individuals exposed to gestational hyperglycemia. The objective of this study was to synthesize the different experimental protocols that have been used to examine the embryos, fetuses, and pups of rats with Gestational Diabetes Mellitus (GDM) induced by streptozotocin (GDM-STZ). In this work, we have developed an integrative literature review, including quantitative methodological approaches that can be applied to studies of GDM-STZ in rats. Three points were highlighted in this study: a) Doses and central routes of STZ administration, and plasma glucose concentration for recognition of GDM-STZ; B) Protocols used for prenatal evaluation; c) Protocols used for the assessment of postnatal development. The doses ranged from 30 to 135 mg/kg for intraperitoneal administration; Between 20 and 65 mg/kg for the intravenous route and 45 mg/kg for the subcutaneous route. The blood glucose values for recognition of GDM were between 97 and 500 mg/dL. Prenatal studies approached diabetic embryopathy associated with central nervous system development and renal function in addition to changes in utero-placental-fetal transport. On the other hand, postnatal studies emphasized the correlation between neonatal macrossomia and postnatal dyslipidemia, postnatal behavioral development and cardiovascular changes. Although there are large methodological differences between the protocols employed, we can conclude from this review that GDM-STZ is still a good model for the studies of the effects of hyperglycemia on the concepts.(AU)

Endoplasmic reticulum stress and renal lesion in mice with combination of high-fat diet and streptozotocin-induced diabetes

PURPOSE: To investigate in the kidney the pathologic changes and expression of GRP78 and CHOP in the Kunming (KM) mice with combination of high-fat diet and streptozotocin-induced diabetes.METHODS: Sixty two male KM mice were randomly divided into a normal control (NC) group (n=20) and a high-fat diet (HFD) group (n=42). After a four-week dietary manipulation, the KM mice in the HFD group were injected intraperitoneally with streptozotocin to induce diabetes. After diabetic models were successfully established, the kidneys were excised and conserved for further test.RESULTS: No significant difference in the body weight was observed after the dietary manipulation (p=0.554). After the streptozotocin was injected, fasting blood glucose levels in the diabetes group (DM) were significantly higher than that in the NC group (p＜0.0001). Glomerular atrophy observed under light microscope in the DM group was more serious compared with the NC group. The expression of GRP78 and CHOP in the kidneys of the mice in the DM group were higher compared with the NC group.CONCLUSION: Renal lesion occurs in the diabetic Kunming mice induced by combination of high-fat diet and low-dose streptozotocin, and endoplasmic reticulum stress and CHOP may contribute to the injury process.(AU)

Low intensity ultrasound therapy induces angiogenesis and persistent inflammation in the chronic phase of the healing process of third degree burn wounds experimentally induced in diabetic and non-diabetic rats

PURPOSE:To evaluate the effects of low intensity ultrasound on the healing process of third degree burn wounds in experimentally induced diabetic Wistar rats.METHODS:One hundred rats were divided into: control group; non-diabetic treated group; diabetic control group; diabetic treated group. The therapy was performed with a 3MHz ultrasound application, pulsed emission at 100Hz frequency, modulated at 20% with a dosage of 0.5W/cm2 during three minutes throughout 30 days. The surgical debridement of the wound was performed once at day 2. The wounds were morphometrically, macroscopically and microscopically evaluated at 3, 7, 14, 21 and 30 days.RESULTS:The wound contraction and collagen quantification were higher in all treated groups. Macroscopically, necrosis was higher in the diabetic control group. Granulation tissue was higher in treated groups during the proliferative and remodeling phase. Microscopically, there were greater mononuclear inflammatory infiltration, angiogenesis and fibroblast quantification in treated groups during the proliferative and remodeling phases.CONCLUSIONS:therapeutic ultrasound is beneficial in the inflammatory and proliferative phases of the healing process because it controlled the necrotic tissue, increased the granulation tissue and wound contraction. However in the remodeling phase it is not beneficial because of the continued angiogenesis and a mononuclear inflammatory infiltration.(AU)

Urethral dysfunction due to alloxan-induced diabetes. Urodynamic and morphological evaluation

PURPOSE: To evaluate the effect of short and long term alloxan-induced diabetes on bladder and urethral function of female rats, and also describing its correlated morphological alterations. METHODS: Thirty five female rats were divided into three groups: G1 (n=9), control group; G2 (n=17), six weeks alloxan-induced diabetic rats; G3 (n=9), 20 weeks alloxan-induced diabetic rats. Functional evaluation was performed by cystometry and simultaneous measurements of the urethral pressure during bladder filling and voiding. Morphological evaluation was also performed with measurement of bladder and urethral fibrosis and collagen content and thickness of lamina propria and smooth muscle layers. RESULTS: The peak bladder pressures and contraction amplitudes were decreased in 100% and 47% of the G3 and G2 groups respectively, when compared to control. Bladder overactivity was observed in 53% of the G2 group. CONCLUSION: Alloxan-induced diabetes urethropathty in female rat was associated to bladder morphological alterations as higher thicknesses of it lamina propria, detrusor and adventicea. (AU)

"Determinação da curva glicêmica e alterações histológicas de camundongos NOD produzidos no ICTB/FIOCRUZ

O diabetes mellitus (DM) ou simplesmente diabetes é uma doença metabólica crônica caracterizada por níveis elevados de glicose no sangue e que leva a sérios danos em diversos órgãos do corpo. É considerada epidemia mundial, sendo atualmente estimado em 425 milhões os adultos diabéticos (1 a cada 11). Seu processo ocorre quando a produção da insulina é insuficiente ou inexistente ou ainda quando o organismo não é capaz de utilizar a insulina que é produzida nas células beta () do pâncreas. Há diversos tipos de DM, porém com maior frequência encontramos a Diabetes mellitus tipo 2 (DM2), causada principalmente pela insuficiência das células do pâncreas; encontramos ainda os tipos: Latent Autoimmune Diabetes in Adults (LADA); Diabetes Gestacional; Diabetes tipo MODY; Diabetes mellitus tipo 1 (DM1) entre outras. A DM1 é geralmente diagnosticada principalmente em crianças e jovens, tem como características a destruição das células , podendo ser considera uma das formas mais agressivas da doença. Um dos principais biomodelos para o estudo da DM1 é o camundongo mutante natural, Inbred, da linhagem Non Obese Diabetic (NOD), pois ele desenvolve o processo autoimune clinica e geneticamente similar a doença em humanos. Porém, diversos fatores podem influenciar no processo autoimune do camundongo NOD, fatores ambientais, genéticos, manejo, sanitário entre outros, informações essas que são extremamente importantes para a pesquisa com o biomodelo sendo necessária a padronização do biomodelo utilizado. Este trabalho teve como objetivo caracterizar o camundongo NOD criado no Instituto de Ciência e Tecnologia em Biomodelos (ICTB-Fiocruz) fornecendo assim informações e características específicas dos animais fornecidos para estudos dentro da Fundação Oswaldo Cruz e parceiros. No desenho experimental proposto neste trabalho buscou-se caracterizar a linhagem nas condições criadas no ICTB, a fim de proporcionar informações essenciais para que sejam desenvolvidas as pesquisas com mais precisão e melhores resultados. Os resultados demonstram que os fatores ambientais possuem grande influencia na expressam fenotípica da linhagem. Observou-se que na colônia mantida no ICTB os animais expressão alta glicêmica de forma tardia (após 20 semanas de vida) porém, conforme a literatura tendem os animais possuem resultados histopatológicos positivos para infiltrado inflamatório no pâncreas mostrando que se o trabalho for realizado com animais mais velhos (após 30 semanas) teremos um resultado tendendo a totalidade dos animais apresentando processo autoimune e diabetes.

Diabetes mellitus (DM) or simply diabetes is a chronic metabolic disorder characterized by high levels of glucose in the blood and leading to serious damage to various organs of the body. Is considered a worldwide epidemic and it is currently estimated at 425 million diabetic adults (1 in 11). Its process occurs when the production of insulin is insufficient or nonexistent or even when the body is not able to use the insulin that is produced in the beta () cells from pancreas. There are several types of DM, but more frequently we find Type 2 diabetes mellitus (DM2), caused mainly by the insufficiency of cells of the pancreas; besides, we can also find the types: LatentAutoimmune Diabetes in Adults (LADA); Gestational diabetes; Diabetes type MODY; and the most aggressive type, Diabetes mellitus type 1 (DM1). DM1 is usually diagnosed mainly in children and young people. It is characterizedby the destruction of -cells, which can be considered one of the most aggressive forms of the disease. One of the main biomodels for the study of DM1 is the natural mutant mouse, Inbred, of the Non Obese Diabetic (NOD) strain as it develops the clinical and genetically similar autoimmune disease in humans. However, several factors may influence the autoimmune process of the NOD mouse, environmental, genetic, management, and sanitary factors among others, information that is extremely important for research with the biomodel being necessary the standardization of the biomodel used. This work aimed to characterize the NOD mouse created at the Institute of Science and Technology in Biomodels (ICTB-Fiocruz) thus providing information and specific characteristics of the animals provided for studies within the Oswaldo Cruz Foundation and partners. The experimental design proposed in this work was aimed at characterizing the lineage in the conditions created in the ICTB, in order to provide essential information for the research to be developed with more precision and better results. Our results demonstrate that the environmental factors have a great influence on the phenotypic expression of the lineage. It was observed that in the colony maintained in the ICTB, the animals expressed late glycemic (after 20 weeks of life), however, according to the literature, animals had positive histopathological results for inflammatory infiltrate in pancreas, showing that if this work would be performed with animals after 30 weeks,it could be possible to have a totality of the animals presenting autoimmune process and diabetes.

COMPARAÇÃO ENTRE 2 PROTOCOLOS PARA INDUÇÃO DO DM2 E AVALIAÇÃO DO EFEITO DO EXERCÍCIO FÍSICO MODERADO SOBRE A LIPOTOXICIDADE E OS EICOSANÓIDES

Os objetivos do presente estudo foram investigar as seguintes hipóteses: 1) a dieta hiperlipídica pode induzir o Diabetes Mellitus tipo 2 (DM2) sem a administração de streptozotocina (STZ); a ingestão de dieta hiperlipídica e hipercalórica causam alterações metabólicas, comportamentais e morfológicas, similares ao DM2 e; 3) a prática de exercício físico moderado tem potencial sobre as alterações metabólicas causadas pelo DM2 e pela dieta hiperlipídica. Para testarmos essas hipóteses foram utilizados 57 ratos Wistar com 8 semanas de idade, distribuídos nos seguintes grupos experimentais: grupo D (N=25) que receberam uma única injeção intraperitoneal de estreptozotocina (STZ diluído em tampão de citrato, pH 4,5 - 25mg/kg de peso corporal do animal) e foram alimentados com dieta hiperlipídica. Para testar o efeito somente da dieta hiperlipídica, o grupo HL (N=8), recebeu uma dieta hiperlipídica, mas não recebeu a injeção de STZ. Animais com idades similares foram utilizados como controle (CO, N=24) e alimentados com dieta balanceada. No final da terceira semana, animais dos grupos CO e D e HL foram subdivididos em dois grupos: sedentário (SE) e exercitado (EF). Os grupos EF foram submetidos a um protocolo de natação durante 6 semanas. Após o protocolo experimental, os grupos D-SE, D-EF e HL-SE apresentaram alterações significativas no ganho de massa, gordura abdominal, ingestão calórica, eficiência alimentar, perfil lipídico e glicemia em jejum e capilar quando comparados aos animais controles. Não houve diferença significativa nas concentrações dos produtos do ácido araquidônico e o tecido renal não apresentou alterações morfológicas. O exercício físico aumentou as lipoproteínas de alta densidade (HDL), mas não alterou os demais parâmetros avaliados. Concluímos que o consumo da dieta hiperlipídica quando associada ao comportamento sedentário pode causar alterações metabólicas similares ao DM2 e que o exercício físico foi eficiente para melhorar o perfil lipídico.

The present study aimed to test whether: 1) the high fat diet can induce T2D without the administration of streptozotocin (STZ); 2) the high fat caloric intake causes metabolic, behavioral and morphological changes, similar to t2D and; 3) the practice of moderate physical exercise is effective to reverse the metabolic changes caused by T2D and of the high fat diet. To test these hypotheses, we used 57 Wistar 8 week old rats. They were splited into the five experimental groups: group D (N = 25) who received a single intraperitoneal dose of streptozotocin (STZ diluted in citrate buffer, pH 4.5-25mg / kg body weight of the animal) and were fed with high fat diet. To test the effect only of the high fat diet, the HL group (N = 8) was fed with high fat diet but did not receive the STZ injection. Animals with similar ages were used as control (CO, N = 24) and fed with a balanced diet. At the end of the third week, animals of CO and D and HL groups were subdivided into two other groups: sedentary (SE) and exercised (EF). EF groups were submitted to swimming for 6 weeks. The D-SE, D-EF and HL-SE groups presented significant changes in body weight gain, abdominal fat gain, caloric intake, food efficiency, lipid profile and fasting and capillary glucose levels, when compared to control groups. There was no significant difference in the concentrations of arachidonic acid products and the renal tissue did not present morphological alterations. Physical exercise increased high density lipoproteins (HDL), but did not change others evaluated parameters. We conclude that consumption of the high fat diet when associated with sedentary behavior may cause metabolic alterations similar to T2D and that physical exercise was efficient to improve the lipid profile.

CROMO E RESTRIÇÃO ENERGÉTICA EM SUBSTITUIÇÃO A RACTOPAMINA NA DIETA DE LEITOAS DOS 100 AOS 125 KG

Este estudo foi conduzido com o objetivo de avaliar a suplementação de cromo e restrição energética em substituição a ractopamina em dieta leitoas em terminação dos 100 aos 125 kg sobre desempenho e características de carcaça. O consumo de gordura saturada em excesso está relacionado com o desenvolvimento de doenças cardiovasculares, diabetes e obesidade em humanos, logo, carcaças suínas com menores teores de gordura são desejáveis. A ractopamina é responsável por modificar o metabolismo animal, promovendo o crescimento, deposição de carne além de diminuir o teor de gordura na carcaça de suínos em terminação. A restrição energética na dieta é outra forma de reduzir a deposição de gordura na carcaça. Além disso, o cromo através da potencialização da ação da insulina, pode promover a utilização da glicose pelas células de forma mais eficiente, reduzindo o processo de lipogênese. Foram utilizadas 60 fêmeas suínas com peso inicial de 98,87±8,13 kg, distribuídas em delineamento de blocos ao acaso com cinco dietas: controle; restrição energética (redução de 150 Kcal de EM/kg de ração), ractopamina (20 ppm), cromo levedura (0,8 ppm) e picolinato de cromo (0,48ppm), com seis repetições por tratamento, com dois animais por unidade experimental. Adotou-se o peso inicial como critério para a formação de blocos. A suplementação de ractopamina, cromo e restrição energética não influenciaram o peso final, ganho de peso diário, consumos diários de ração, proteína, lisina digestível e energia metabolizável. A suplementação com 20 ppm de ractopamina melhora a conversão alimentar de fêmeas suínas em terminação. O peso de carcaça quente melhora com a inclusão de 20 ppm de ractopamina na dieta. O cromo levedura aumenta o peso de carcaça de quente em relação a dieta controle e restrição energética de leitoas em terminação. Dietas contendo ractopamina, cromo levedura ou picolinato de cromo expressam aumento da quantidade de carne magra e índice de bonificação das carcaças em comparação às dietas controle ou com restrição energética de 150 Kcal/kg de energia metabolizável. A restrição energética da dieta em 150 Kcal de EM não prejudica o desempenho e as características de carcaça das leitoas.

This study was conducted with the objective of evaluating chromium supplementation and energetic restriction in replacement of ractopamine in finishing pigs diets from 100 to 125 kg on performance and carcass characteristics. Excess consumption of saturated fat is related to the development of cardiovascular diseases, diabetes and obesity, the fat present in the carcasses is undesirable. The ractopamine is responsible for modifying the animal metabolism, promoting growth, meat deposition, and decreasing the fat content in the finishing pig carcass. Dietary energy restriction may be another way of reducing fat deposition in the carcass. Chromium potentiates the action of insulin, promoting the use of glucose by cells more efficiently, reducing the process of lipogenesis. Sixty females were used, distributed in a randomized complete block design with five diets: control; energy restriction (reduction of 150 Kcal ME / kg of feed), ractopamine (20 ppm), chromium yeast (0.8 ppm) and of chromium picolinate (0.48 ppm) with six replicates per treatment with two animals per experimental unit. The initial weight was adopted as a criterion for the formation of blocks. The supplementation of ractopamine, chromium and energy restriction did not influence the final weight, the daily weight gain, the daily intake of feed, protein, digestible lysine and metabolizable energy. Supplementation with 20 ppm of ractopamine improves the feed conversion of the finishing pigs. The hot carcass weight improves with the inclusion of 20 ppm ractopamine in the diet. The chromium yeast increases the weight of the hot carcass in relation to the control diet and energy restriction of finishing pigs. Diets containing ractopamine, chromium yeast or chromium picolinate increases lean meat content and carcass bonus index in comparison with diets control or with energy restriction of 150 Kcal kg of metabolizable energy. The energy restriction of the diet in 150 Kcal of ME does not affect the performance and the carcass characteristics of the finishing pigs.

EFEITO DA INGESTÃO DE DIFERENTES FONTES E CONCENTRAÇÕES DE LIPÍDEOS SOBRE PARÂMETROS METABÓLICOS DE RATOS WISTAR OBESOS

A obesidade é um problema de saúde pública que atinge proporções epidêmicas. É uma doença crônica caracterizada pelo acúmulo excessivo de gordura corporal. Dentre as suas comorbidades estão as doenças cardiovasculares, o diabetes mellitus e as dislipidemias. Nesse sentido, no presente estudo avaliou-se o efeito do consumo de diferentes fontes e concentrações de lipídeos inseridos na dieta, sobre parâmetros metabólicos de ratos Wistar previamente induzidos a obesidade por dieta hiperlipídica. O delineamento experimental foi inteiramente casualizado em esquema fatorial 3x2, com seis repetições por tratamento. Um total de 36 ratos Wistar foram alimentados durante 12 semanas com dieta hiperlipídica contendo 20% de banha suína, com o intuito de torná-los metabolicamente obesos. Após esse período, os animais foram divididos em seis grupos e passaram a receber dietas nas concentrações lipídicas de 5% ou 20% de banha suína (BA), óleo de soja (OS) ou óleo de peixe (OP) por 4 semanas. Os dados obtidos foram submetidos à análise de variância (two way) seguidos de teste post hoc de Tukey (p<0,05). Os grupos que consumiram OP, independente da concentração utilizada, apresentaram menor ganho de peso, assim como menores dosagens séricas de triacilgliceróis (TAG), colesterol total e frações (HDL-c, LDL-c+VLDL-c), atividade de aspartato aminotransferase (AST), índice aterogênico, concentração de gordura na carcaça, índice de Lee e contagem global de leucócitos (p<0,05). Os mesmos parâmetros foram maiores nos grupos que consumiram BA (p<0,05). Apenas nas concentrações de 20% de OP (p<0,05) houve redução dos níveis séricos de glicose, da atividade de alanina aminotransferases (ALT) e de gama glutamiltransferase (GGT) em comparação aos demais grupos de mesmo teor lipídico (20%). Os grupos que consumiram OS apresentaram valores similares ao grupo OP no que se refere ao ganho de peso e reduzidos em relação ao grupo BA (p<0,05). No entanto, os níveis de colesterol total e frações, índice aterogênico, concentração de gordura na carcaça, índice de Lee e contagem global de leucócitos foram semelhantes aos grupos que consumiram BA (aumentados em relação ao grupo OP). Nos demais parâmetros o grupo OS apresentou resultados intermediários aos outros dois tratamentos. A partir das análises obtidas, conclui-se que a ingestão de dieta rica em óleo de peixe foi capaz de modular, positivamente, as alterações metabólicas decorrentes da dieta hiperlipídica contendo 20% de banha.

Obesity is a public health issue that has reached epidemic proportions. It is a chronic disease characterized by the excessive accumulation of body fat. Among its comorbidities are cardiovascular diseases, diabetes mellitus and dyslipidemia. In this sense, this study evaluated the effect of the consumption of different sources and inserted concentrations of lipids in the diet over metabolic parameters of Wistar rats, previously obesity-induced by high-fat diet. The experimental design was completely randomized in a 3x2 factorial arrangement with six replicates per treatment. A total of 36 Wistar rats were fed high-fat diet containing 20% of lard for 12 weeks, in order to cause metabolic obesity. After this period, the animals were divided into six groups, and fed diets with lipid concentrations of 5% or 20% of lard (BA), soybean oil (OS) or fish oil (OP), for 4 weeks. The data were submitted to analysis of variance (two way) followed by post hoc Tukey test (p<0.05). The groups that consumed OP, regardless of the concentration, showed less weight gain and lower serum levels of triacylglycerol (TAG), total cholesterol and fractions (HDL-c, LDL-c+VLDL-c), aspartate aminotransferase (AST) activity, atherogenic index, concentration of fat in the carcass, Lee index and total leukocyte (p<0.05). The same parameters presented higher values in the group that consumed BA (p<0.05). Only in the concentration of 20% OP (p<0.05) did serum glucose, alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) activities decrease when compared to the other groups with the same fat content (20%). The groups that consumed OS showed similar values to the OP group regarding weight gain, and reduced values when compared to the BA group (p<0.05). However, total levels of cholesterol and lipoproteins, atherogenic index, concentration of fat in the carcass, Lee index and total leukocyte count were similar in the groups that consumed BA (increased in relation to the OP group). For the remaining parameters, the OS group had intermediate results regarding the other two treatments. With the results obtained, we concluded that the diet intake of fish oil was able to positively modulate metabolic changes resulting from the high-fat diet containing 20%fat.

Fructose and NAFLD: metabolic implications and models of induction in rats / Frutose e NAFLD: implicações metabólicas e modelos de indução em ratos

PURPOSE: The increase in fructose consumption is paralleled by a higher incidence of obesity worldwide. This monosaccharide is linked to metabolic syndrome, being associated with hypertriglyceridemia, hypertension, insulin resistance and diabetes mellitus. It is metabolized principally in the liver, where it can be converted into fatty acids, which are stored in the form of triglycerides leading to NAFLD. Several models of NAFLD use diets high in simple carbohydrates. Thus, this study aimed to describe the major metabolic changes caused by excessive consumption of fructose in humans and animals and to present liver abnormalities resulting from high intakes of fructose in different periods of consumption and experimental designs in Wistar rats. METHODS: Two groups of rats were fasted for 48 hours and reefed for 24 or 48 hours with a diet containing 63 percent fructose. Another group of rats was fed an diet with 63 percent fructose for 90 days. RESULTS: Refeeding for 24 hours caused accumulation of large amounts of fat, compromising 100 percent of the hepatocytes. The amount of liver fat in animals refed for 48 hours decreased, remaining mostly in zone 2 (medium-zonal). In liver plates of Wistar rats fed 63 percent fructose for 45, 60 and 90 days it's possible to see that there is an increase in hepatocytes with fat accumulation according to the increased time; hepatic steatosis, however, is mild, compromising about 20 percent of the hepatocytes. CONCLUSIONS: Fructose is highly lipogenic, however the induction of chronic models in NAFLD requires long periods of treatment. The acute supply for 24 or 48 hours, fasted rats can cause big changes, liver steatosis with macrovesicular in all lobular zones.(AU)

OBJETIVO: O aumento do consumo de frutose é concomitante a maior incidência mundial de obesidade. Este monossacarídeo está relacionado à Síndrome Metabólica, sendo vinculado à hipertrigliceridemia, hipertensão arterial, resistência à insulina e diabetes mellitus. É metabolizada principalmente no fígado, onde pode ser convertida em ácidos graxos, os quais serão estocados na forma de trigligérides ocasionando a esteatose hepática não alcoólica (NAFLD). Vários modelos de NAFLD utilizam dietas ricas em carboidratos simples. Desta forma, este trabalho teve como objetivos descrever as principais alterações metabólicas causadas pelo consumo excessivo de frutose em humanos e em animais e apresentar as alterações hepáticas decorrentes da alta ingestão de frutose em diferentes períodos de consumo e desenhos experimentais em ratos Wistar. MÉTODOS: Dois grupos de ratos Wistar foram mantidos em jejum durante 48 horas e realimentados por 24 ou 48 horas com dieta contendo 63 por cento de frutose. Outro grupo de ratos Wistar foi alimentado com 63 por cento de frutose durante 90 dias. RESULTADOS: A realimentação por 24 horas provocou acúmulo de grande quantidade de gordura. A quantidade de gordura hepática nos animais realimentados por 48 horas diminuiu, mantendo-se principalmente nas zona 2 (medio-zonal). Em fígados de ratos Wistar alimentados com 63 por cento de frutose até 90 dias foi possível observar que há aumento de hepatócitos com acúmulo de gordura consequente ao aumento do tempo, no entanto a esteatose hepática é leve (20 por cento). CONCLUSÕES: A frutose é altamente lipogênica, no entanto a indução de NAFLD em modelos crônicos necessita de longos períodos de tratamento. A oferta aguda, por 24 ou 48 horas, a ratos mantidos em jejum é capaz de ocasionar grandes mudanças hepáticas, com presença de esteatose macrovesicular em todas as zonas lobulares.(AU)

Metformina no desempenho e composição corporal de tilápia-do-Nilo (Oreochromis niloticus) alimentada com duas concentrações de carboidratos

Apesar do carboidrato ser o macronutriente que fornece a energia mais barata na composição de uma dieta, peixes possuem capacidade limitada para utilização de um de seus importantes constituintes: a glicose. A metformina (MET) é uma droga utilizada para o tratamento de diabetes, cuja função é reduzir os níveis de glicose no sangue, melhorando, assim, sua utilização pelos mamíferos. O objetivo deste estudo foi avaliar o desempenho da tilápia-do-Nilo com e sem a suplementação de 0,2% de MET, em dietas com 24% (24C) e 48% de carboidrato (48C), representando concentrações adequada e excessiva, respectivamente, deste macronutriente. Quatro grupos de 20 juvenis de tilápia-do-Nilo (22,00 ± 1,45 g) foram alimentados com cada uma das dietas experimentais duas vezes ao dia, por 80 dias. Houve interação entre a concentração de carboidrato e a presença de MET para a matéria seca e extrato etéreo corporal, as quais, na presença da droga, aumentaram nos peixes que receberam a dieta 48C, mas diminuíram naqueles que receberam a dieta 24C. Não houve efeito da suplementação de MET no desempenho dos peixes. Entretanto, o aumento na concentração de carboidrato na dieta propiciou o acúmulo de gordura corporal, aumentando significativamente os índices hepato e viscerossomáticos, enquanto o desempenho dos peixes diminuiu

Despite the carbohydrate is the macronutrient that provides the cheapest energy in the composition of a diet, fish have limited ability to use one of its major constituents: glucose. Metformin (MET) is a drug used for the treatment of diabetes, whose function is to reduce the glucose levels in the blood, thus improving its use by mammals. The objective of this study was to evaluate the performance of Nile tilapia with or without supplementation of 0.2% MET in diets with 24% (24C) and 48% carbohydrate (48C), representing adequate and excessive concentrations of this macronutrient, respectively. Four groups of 20 juveniles of Nile tilapia (22.00 ± 1.45 g) were fed each one of the experimental diets twice daily for 80 days. There was a significant interaction between the dietary concentration of carbohydrate and the presence of MET for body dry matter and ether extract. Those body composition fractions increased in the presence of the drug in fish fed diet 48C but decreased in those fed diet 24C. There was no effect of MET supplementation on fish performance. However, the increase in dietary carbohydrate concentration led to the accumulation of body fat, significantly increasing the hepato and viscerossomatic indexes, while decreased fish performance

Association of diabetes and cigarette smoke exposure on the glycemia and liver glycogen of pregnant Wistar rats / Associação entre diabetes e exposição à fumaça de cigarro sobre a glicemia e glicogênio hepático de ratas Wistar prenhes

PURPOSE: To evaluate cigarette smoke exposure and/or diabetes association effects on the glycemia and liver glycogen levels of pregnant Wistar rats. METHODS: 60 adult rats were randomly distributed into (n=10/group): non-diabetic exposed to filtered air (G1); non-diabetic exposed to cigarette smoke only before pregnancy (G2); non-diabetic exposed to cigarette smoke before and during pregnancy (G3); diabetic exposed to filtered air (G4); diabetic exposed to cigarette smoke only before pregnancy (G5), and diabetic exposed to cigarette smoke before and during pregnancy (G6). Glycemia was determined at days 0 and 21 of pregnancy. Liver samples were collected for liver glycogen determinations. RESULTS: At day 21 of pregnancy, glycemia was higher in G5 and G6 compared to G4 group. G2 (2.43±0.43), G3 (3.20±0.49), G4 (2.62±0.34), G5 (2.65±0.27) and G6 groups (1.94±0.35) presented decreased liver glycogen concentrations compared to G1 (4.20±0.18 mg/100mg liver tissue) (p<0.05). G5 and G6 groups presented decreased maternal weight gain and litter weight. CONCLUSIONS: Severe diabetes and cigarette smoke exposure, alone or associated, caused impairment in liver glycogen storage at term pregnancy. Due to the fact that liver glycogen storages were considered determinant for glucose tolerance, it is relevant to point out a rigid clinical glycemic control and to stop smoking so earlier in pregnancy programming.(AU)

OBJETIVO: Avaliar a associação da exposição à fumaça de cigarro e/ou diabete sobre a glicemia e concentrações de glicogênio hepático em ratas Wistar prenhes. MÉTODOS: 60 ratas adultas foram distribuídas aleatoriamente em seis grupos (n=10/grupo): não-diabético exposto ao ar filtrado (G1); não-diabético exposto à fumaça de cigarro antes da prenhez (G2); não-diabético exposto à fumaça de cigarro antes e durante a prenhez (G3); diabético exposto ao ar filtrado (G4); diabético exposto à fumaça de cigarro antes da prenhez (G5); diabético exposto à fumaça de cigarro antes e durante a prenhez (G6). A glicemia foi determinada nos dias 0 e 21 de prenhez. Foram coletadas amostras de fígado para dosagens de glicogênio. RESULTADOS: No 21º dia de prenhez, a glicemia foi maior nos grupos G5 e G6 comparados ao grupo G4. Os grupos G2 (2,43±0,43), G3 (3,20±0,49), G4 (2,62±0,34), G5 (2,65±0,27) e G6 (1,94±0,35) apresentaram concentrações de glicogênio diminuídas comparados ao grupo G1 (4,20±0,18 mg/100mg) (p <0.05). Os grupos G5 e G6 apresentaram ganho de peso materno e peso da ninhada diminuídos. CONCLUSÕES: O diabete grave e a exposição à fumaça de cigarro, sozinhos ou associados, causaram prejuízo no armazenamento de glicogênio na prenhez a termo. Devido ao fato dos estoques de glicogênio serem determinantes para a tolerância à glicose, é imprescindível indicar um rígido controle glicêmico e deixar de fumar antes da gestação.(AU)

Glutamine or whey-protein supplementation on alloxan-induced diabetic rats. Effects on CD4+ and CD8+ lymphocytes / Efeitos da oferta de glutamina ou de proteína do soro de leite sobre os linfócitos CD4+ e CD8+ em ratos diabéticos aloxano induzidos

PURPOSE: To evaluate the effects of glutamine (L-Gln) or whey-protein supplementation on CD4+ and CD8+ lymphocytes in alloxan-induced diabetic rats. METHODS: Thirty-two healthy male Wistar rats were used in the experiment. Eight rats served as baseline controls (G-1). The remaining 24 animals received alloxan 150mg/Kg intraperitonially dissolved in buffer solution and were equally distributed in 3 subgroups, upon induction of diabetes mellitus, and treated as follows: (G2): saline, 2.0ml; (G3): glutamine solution (0.7g/kg), 2.0 ml; and (G4): whey-protein (WPS) solution (0.7g/kg), 2.0 ml. All solutions were administered by daily 7:00 AM gavages during 30 days. Next, arterial blood samples (3.0 ml) were collected from anesthetized rats for CD4+ and CD8+ lymphocyte count through flow cytometry technology. RESULTS: CD4+ and CD8+ counts decreased significantly in all groups compared with baseline values (G1). G2 rats CD4+/CD8+ ratio decreased significantly compared with G1. CD4+/CD8+ ratio increased significantly (>260 percent) in L-Gln treated group (G3) compared with saline-treated rats (G2). There were no statistical differences in lymphocyte counts (CD4+ and CD8+) between L-Gln (G3) and saline-treated (G2) groups. There was a significant reduction in CD8+ cell count compared with CD4+ cell count in L-Gln treated rats (G3). CONCLUSION: The offer of L-Gln to experimental diabetic rats enhances the immunologic response to infection.(AU)

OBJETIVO: Avaliar os efeitos da suplementação de glutamina ou proteína do soro de leite ( PSL) sobre os linfócitos CD4+ e CD8+ em ratos diabéticos aloxano induzidos. MÉTODOS: Trinta e dois ratos Wistar machos, saudáveis, foram utilizados no estudo. Oito ratos foram usados como controles basais (G1). Os 24 animais remanescentes foram equitativamente distribuídos em 3 subgrupos, após indução do diabetes mellitus por injeção intraperitonial de aloxano (150mg/Kg) e tratados como se segue: (G2): salina; (G3): 2,0 ml de solução de glutamina (0,75g/Kg);(G4): PSL, (0,7g/Kg), 2,0ml. Todas as soluções foram administradas por gavagem, diariamente, cada 7:00 h, durante 30 dias. Após esse período, foram coletadas amostradas de sangue arterial para contagem de linfócitos CD4+ e CD8+ por citometria de fluxo. RESULTADOS: A população de linfócitos CD4+ e CD8+ diminuiu significantemente em todos os grupos em comparação aos valores encontrados no grupo G1. A razão CD4+/CD8+ foi significantemente maior (>260 por cento) nos ratos tratados com L-Gln que nos ratos tratados com salina (G2). Não se observaram diferenças significantes na população de linfócitos CD4+ e CD8+ entre os grupos G3 e G2. Houve redução significante do número de células CD8+ quando comparado ao número de células CD4+ nos ratos tratados com L-Gln (G3). CONCLUSÃO: A oferta de L-Gln em ratos diabéticos aloxano-induzidos melhora a resposta imunológica à infecção.(AU)

Estudo comparativo entre cinco diferentes tratamentos sobre as alterações clínicas e laboratoriais do rato diabético induzido pela aloxana / Comparative study among five different treatments on the clinical and laboratory changes of the alloxan-induced diabetic rats

OBJETIVOS: Este estudo visa a analisar os efeitos, a longo prazo, de cinco diferentes tratamentos sobre o controle metabólico de ratos diabéticos aloxânicos. MÉTODOS: Foram analisados 7 grupos experimentais, com 50 ratos cada um, sendo: GN o grupo controle normal; GD o grupo controle diabético, sem tratamento; GI, GA e GIA os grupos tratados, respectivamente, com insulina, acarbose e associação insulina + acarbose; GTIL o grupo tratado com transplante de ilhotas de Langerhans; e o GTPD o grupo tratado com transplante pancreatoduodenal heterotópico. Parâmetros clínicos (peso, ingestão hídrica, ingestão alimentar e diurese) e laboratoriais (glicemia, glicose urinária e insulina plasmática) foram avaliados em todos os animais, no início do experimento, e após 1, 3, 6, 9 e 12 meses de seguimento. RESULTADOS: A exceção do GN, mortalidade foi observada em todos os grupos experimentais no seguimento de 12 meses (GD= 50 por cento; GI= 20 por cento; GA= 26 por cento; GIA= 18 por cento; GTIL= 4 por cento; GTPD= 20 por cento). Em GD, GI, GA e GIA os óbitos ocorreram por distúrbios metabólicos ou hidroeletrolíticos e/ou pneumonia, diarréia e caquexia; em GTIL e GTPD todos os óbitos ocorreram por falhas técnicas no pós-operatório até 72h. Animais dos grupos GI, GA e GIA tiveram melhora significativa (p < 0,05) de todos os parâmetros clínicos e laboratoriais observados em ratos diabéticos, sem diferença de efetividade entre os tratamentos. Porém, os resultados observados nestes grupos, biologicamente não foram comparáveis aos observados em GTIL e GTPD, onde observou-se correção completa, aos níveis normais, de todas as variáveis analisadas (p<0,01). CONCLUSÕES: Os tratamentos convencionais com insulina, acarbose e insulina + acarbose melhoraram o estado diabético grave dos ratos tratados, contudo, a eficácia dos tratamentos foi significativamente inferior à oferecida pelo GTIL e GTPD. (AU)