Evaluation of Glycemic and Lipid Profile of Offspring of Diabetic Wistar Rats Treated with Malpighia emarginata Juice

Knowing that maternal diabetes is related to hyperglycemia and fetal hyperinsulinemia, which affect the lipid metabolism, the aim of this study was to evaluate the effects of Malpighia emarginata (acerola) juice on the glycemic and lipid profile of offspring of diabetic and nondiabetic Wistar rats. The adult offspring of non-diabetic dams and of dams with severe streptozotocin-induced diabetes were divided into groups: G1, offspring (of control dams) treated with water, G2, offspring (of diabetic dams) treated with water, G3, male offspring (of control dams) treated with acerola juice, and G4, male offspring (of diabetic dams) treated with acerola juice. The offspring of diabetic dams treated with acerola juice showed significantly decreased levels of glucose, cholesterol, triglycerides, and increased HDL-c. The use of acerola juice is a potential strategy to aid in the prevention of DM and dyslipidemia and its complications or to act as an auxiliary in the treatment of these diseases.

Influence of moderate physical training on the GH/IGF-1 axis in diabetic rats

The influence of moderate physical training on serum growth hormone (GH), insulin-like growth factor -1 (IGF-1) and binding protein ( IGFBP-3) in experimental diabetic rats was investigated. Male Wistar rats were divided into 4 groups, sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). Experimental diabetes was induced of Alloxan (35mg/b.w.) the training program consisted by swimming 5 days/week, 1 h/day, supporting a load of 2.5% b.w., during 6 weeks. Then, the rats were sacrificed and blood was collected for determinations of serum glucose, insulin, GH, IGF-1 and IGFBP-3. Samples of liver were used to evaluate glycogen, protein and DNA contents. The results were analyzed by ANOVA, and Bonferroni test and the significance level was set at 2.5%. Diabetes decreased serum GH, IGF-1, IGFBP-3 and liver glycogen stores in SD group. Physical training promoted increase in serum IGF-1 in both TC and TD groups (SC=82 +/- 15; TC= 1 03 +/- 13; SD=77 +/- 16; TD= 112 +/- 29 ng/ml) and liver glycogen store in TD group when compared to SD (SC=5.2 +/- 1.2; TC= 6.2 +/- 1; SD=2 +/- 0.5; TD=5 +/- 1.8 mg/100mg). Therefore, physical training contributes to the increase in liver glycogen content and to rise of insulin-like growth factor level in diabetic rats. It was concluded that moderate physical training promotes important adaptations related to GH-IGF-1 axis in diabetic organisms.

Oxidative stress markers and apoptosis in the prostate of diabetic rats and the influence of vitamin C treatment

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A influência do ultrassom e do treinamento físico sobre os triglicérides séricos e intramusculares em ratos diabéticos experimentais

O ultrassom terapêutico é visto hoje como um dos recursos mais utilizados na prática da medicina clínica e o exercício físico é consolidado como uma terapêutica eficaz e eficiente em diversos casos, porém ainda pouco investigados em conjunto; por isso, o presente trabalho tem como objetivo analisar a influência do ultrassom e do exercício físico sobre as concentrações de triglicérides sérico e intramusculares (IMTG) em ratos diabéticos experimentais. Foram utilizados ratos Wistar adultos divididos em oitos grupos: Diabéticos Sedentários (DS), Diabéticos Treinados (DT), Diabéticos Sedentários e Ultrassom (DSUs), Diabéticos Treinados e Ultrassom (DTUs), Controle Sedentário (CS), Controle Treinado (CT), Controle Sedentário e Ultrassom (CSUs), Controle Treinado e Ultrassom (CTUs). O protocolo de treinamento constituía de natação cinco dias por semana, 30 minutos, por dia com uma carga máxima equivalente a 8% da massa corporal, durante três semanas. A terapia ultrassônica foi realizada cinco dias por semana, durante duas semanas, com intensidade de 0,2W/cm² e frequência de 1,0MHz. Não houve diferenças significativas nos triglicerídeos séricos e nos músculo Tibial Anterior e Gastrocnêmio. Para o músculo Sóleo as concentrações dos grupos diabéticos foram menores comparados com as dos grupos controles e também entre os grupos DT e DTUs comparado com DS e DSUS, sendo que treinados apresentaram as menores concentrações. O ultrassom pulsado na intensidade proposta não influenciou as concentrações séricas de triglicerídeos nem de IMTG. Porém o exercício físico foi eficaz em reduzir IMTG no músculo Sóleo.

Role of metabolic control on diabetic nephropathy

OBJETIVO: Os autores relatam a influência do controle metabólico do diabetes, experimentalmente induzido no rato, sobre a nefropatia diabética. Eles observaram o efeito da insulina, da acarbose, um inibidor da glicosidase, e de dois agentes combinados sobre o controle metabólico e o desenvolvimento da expansão mesangial de glomérulos renais, no diabetes induzido pela aloxana no rato. MÉTODOS: Usando 5 grupos de ratos Wistar assim definidos: Normal(N), diabéticos não-tratados (D), diabéticos tratados com acarbose (AD); diabéticos tratados com insulina (ID) e diabéticos tratados com insulina associada à acarbose (IAD) foram avaliados os seguintes parâmetros: peso corporal, ingestão alimentar, ingestão hídrica, diurese, níveis de glicose sanguínea e urinária e as lesões renais: alargamento mesangial e vacuolização de células tubulares, usando contagem semi-quantitativa 1, 3, 6, 9 e 12 meses após a indução do diabetes. RESULTADOS: Houve acentuado aumento da glicemia, dos níveis de glicose na urina, da diurese, da ingestão hídrica e alimentar, e progressiva perda de peso nos ratos diabéticos, enquanto que os ratos diabéticos tratados exibiram melhora significativa destes parâmetros, sendo os ratos tratados com insulina + acarbose os que apresentaram controle metabólico mais satisfatório. Houve um significativo alargamento mesangial nos ratos diabéticos quando comparado ao observado nos ratos normais, desde o 3º até o 12º mês após a indução do diabetes, sendo observada diferença significativa entre os animais tratados com acarbose + insulina e os ratos diabéticos não-tratados. Não houve diferença significativa entre os animais tratados somente com acarbose ou com insulina quando comparados com ratos diabéticos não-tratados. CONCLUSÃO: Os autores discutem os resultados abordando o papel do controle metabólico do diabetes na prevenção da nefropatia diabética.

EFFECTS OF CYCLOSPORINE-A IMMUNOSUPPRESSION ON PANCREATICODUODENAL TRANSPLANTATION IN ALLOXAN-DIABETIC RATS

1. Forty-five outbred Wistar rats were randomly assigned to three experimental groups: GI, 10 non-diabetic control rats; GII, 10 alloxan-diabetic control rats; GIII, 25 alloxan-diabetic tats which received pancreaticoduodenal transplantation (PDT) from normal Wistar donor rats and were immunosuppressed with cyclosporin A (Cy-A), 10 mg kg body weight-1 day-1, administered intraperitoneally for 30 days.2. In parallel, 15 alloxan-diabetic inbred Wistar rats received isogeneic PDT from normal Wistar donor rats.3. Cy-A prevented graft rejection in the 15 surviving animals in group III. These observations were confirmed by clinical and biochemical parameters (body weight, urine output, water and food intake, blood and urinary glucose and plasma insulin) and by histology and immunohistochemistry of the pancreas.4. However, Cy-A was associated with 60% of the infectious complications in transplanted rats leading to 40% mortality. Pulmonary infections were the main cause of death. There were no side effects of immunosuppression on the pancreas. Infections were not significant in inbred rats submitted to PDT.

Effect of long-term treatment with insulin and/or acarbose on glomerular basement membrane thickening in alloxan-diabetic rats

Acarbose is a competitive inhibitor of the intestinal alpha-glycosidases, that can delay absorption of intestinal carbohydrates causing their malabsorption. In the present paper we studied the effects of insulin, acarbose and their association on glomerular basement membrane thickening in alloxan-diabetic rats. Twenty-five male and female Wistar rats, approximately 3 months old at the beginning of the experiment, were assigned randomly to each of five experimental groups: normal control rats, alloxan-diabetic control rats, alloxan-diabetic rats treated with acarbose, alloxan-diabetic rats treated with insulin, and alloxan-diabetic rats treated with insulin plus acarbose. Alloxan was administered in a single iv dose of 42 mg/kg body weight. Insulin was given subcutaneously at doses of 18 to 30 IU/kg corrected daily on the basis of glycosuria and ketonuria. Acarbose was given mixed with rat chow in a dose of 50 mg/100 g chow. Body weight, water and food intake and diuresis, as well as blood and urine glucose were determined after 1, 3, 6, 9, and 12 months of treatment. Glomerular basement membrane (GBM) thickening was determined by electron microscopy at the same times. Clear clinical and laboratory signs of severe diabetes, with blood glucose levels above 200 mg/dl and urine glucose above 3000 mg/dl, were observed in all alloxan-diabetic control rats, in all periods of follow-up, whereas administration of insulin or acarbose reduced the blood glucose levels of treated groups. The most satisfactory control of blood and urine glucose was observed in animals treated with both insulin and acarbose. However, diarrhea was observed in diabetic rats treated with acarbose associated or not with insulin. GBM thickening was correlated with age in all groups. Beginning at six months after diabetes induction, the GBM of untreated diabetic rats was significantly thicker (mean +/- SEM, 4.446 +/- 0.45 mm) than that of normal rats (2.977 +/- 0.63 mm). Both insulin and acarbose prevented GBM thickening and their combination induced thickening similar to the age-dependent thickening observed for normal rats of the same age. We conclude that acarbose when combined with insulin may be a good option in the control of diabetes and its renal complications.

Collagen and reticular fibers in left ventricular muscle in diabetic rats: Physical exercise prevents its changes?

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cold-acclimation improves cold-tolerance of diabetic rats

1. 1. The aim of these experiments was to study the extent to which previous cold-acclimation improves the cold-tolerance of diabetic rats. 2. 2. Alloxan diabetic rats (fasting blood glucose higher than 200mg/dl) were used in the experiments. 3. 3. In Expt. 1, non-cold-acclimated control and diabetic rats were exposed to cold environment (7-9°C), and the percentage of survival calculated during a 12-day experimental period. In Expt. 2, the rats were previously cold-acelimated before alloxan or saline injection (diabetic and control cold-acclimated rats) and the survival rate was also assessed during a 12-day period in the cold. 4. 4. The percentage of survival of the non-cold-acclimated diabetic rats (Expt.l) was 19% compared with 79% of the diabetic cold-acclimated animals (Expt. 2). There were no deaths in the control groups. 5. 5. Cold-acclimated diabetic rats maintained a near-normal thermogenic response after noradrenaline injection. This response was impaired in non-cold-acclimated diabetic rats. 6. 6. The results of these experiments suggest that the enhanced cold-tolerance of diabetic cold-acclimated rats could be related to the increased sympathetic activity and enhanced insulin sensitivity in thermogenic tissues, such as brown fat. © 1987.

Müller cells and diabetic retinopathy.

Müller cells provide nutrition for neural cells. We studied the structure and ultrastructure of Müller cells in the retina of thirty 3-month old Wistar rats, divided equally into 3 groups: normal rats, alloxan diabetic rats and treated alloxan diabetic rats, 1 and 12 months after induction of diabetes. We observed that the Müller cell nuclei under light microscope examination had hexagonal shape and higher density than the other nuclei. Differences between groups could be observed only by electron microscopy. In the diabetic rats, Müller cells presented dispersion of nuclear chromatin and electrondense nuclear granulations, with the presence of increased glycogen, dense bodies and lysosomes in the cytoplasm. The alterations were more frequent in the perivascular region and at 12 months. The treated diabetic rats exhibited some alterations we observed in diabetic rats, but these alterations were less intense. We conclude that, despite the treatment, the diabetic retinopathy continues to evolve.

Transplante pancreato-duodenal em ratos com microcirurgia. A téchnica e os resultados após 12 anos de experimentação

In this study we present the technical details, adaptations and modifications of the original procedure of pancreaticoduodenal transplantation in rats described by Lee et al. in 1972. We also present the results and technical failures observed in a follow-up of 12 years. From March, 1982 to December, 1994, we performed in the Laboratory of Surgical Technique and Experimental Surgery of Faculty of Medicine, Botucatu - UNESP, Brazil, 665 duodenopancreatectomies in donor rats and 592 surgeries for revascularization of the pancreatic graft in recipient animals. The observed percentage of technical failures in donor rats was 11% due to bleeding and/or vascular complications, irregular flushing of the graft with saline and respiratory insufficiency. In recipients of grafts, we observed a percentage of technical failures of 22,5% due to porto-caval thrombosis, vascular bleeding, pancreatitis and graft ischemia. In both surgeries, the successful results are directly related to the technical performance of the surgeon and the cares in the postoperative period.

Efeitos do tratamento oral com sulfato de vanadila em ratos diabeticos jovens

This work intends to evaluate the effects of oral vanadyl treatment (VOSO 4, 1 mg/mL) in young streptozotocin-diabetic rats during 19 and 29 days. In several times of treatment the rats were monitored to determine body weight, food and water intakes, glycemia, and the urinary excretion of glucose and urea. The animals were killed in the 19(th) and 29(th) days, and the glycemia level was determined again, as well as the weight of pancreas, muscles (Soleus and Extensor digitorum longus - EDL) and adipose tissues (epididymal and retroperitoneal). The results showed that the treatment of young diabetic rats with VOSO 4 promotes the reduction of hyperglycemia (p < 0.01), food (p < 0.01) and water intakes (p < 0.05) and body weight (p < 0.05). Neither the tissues and pancreas weights nor the urinary urea level of the treatment group varied in comparison to the control group. In conclusion, the vanadyl treatment in the studied period is able to reduce the main metabolic alterations often found in diabetes. These data are very useful and important for the future experiments to verify the effects of vanadyl sulfate on muscle protein metabolism in diabetic rats.

Evaluation of toxicity after one-months treatment with Bauhinia forficata decoction in streptozotocin-induced diabetic rats

Background: Previous experiments have shown that a decoction of Bauhinia forficata leaves reduces the changes in carbohydrate and protein metabolism that occur in rats with streptozotocin-induced diabetes. In the present investigation, the serum activities of enzymes known to be reliable toxicity markers were monitored in normal and streptozotocin-diabetic rats to discover whether the use of B. forficata decoction has toxic effects on liver, muscle or pancreas tissue or on renal microcirculation. Methods: An experimental group of normal and streptozotocin-diabetic rats received an aqueous decoction of fresh B. forficata leaves (150 g/L) by mouth for 33 days while a control group of normal and diabetic rats received water for the same length of time. The serum activity of the toxicity markers lactate dehydrogenase, creatine kinase, amylase, angiotensin-converting enzyme and bilirubin were assayed before receiving B. forficata decoction and on day 19 and 33 of treatment. Results: The toxicity markers in normal and diabetic rats were not altered by the diabetes itself nor by treatment with decoction. Whether or not they received B. forficata decoction the normal rats showed a significant increase in serum amylase activity during the experimental period while there was a tendency for the diabetic rats, both treated and untreated with decoction, to have lower serum amylase activities than the normal rats. Conclusions: Administration of an aqueous decoction of B. forficata is a potential treatment for diabetes and does not produce toxic effects measurable with the enzyme markers used in our study. © 2004 Pepato et al; licensee BioMed Central Ltd.

Biochemical evaluation of glycemic levels of long-term tacrolimus therapy in rats

One of the more serious complications following transplantation is the development of post-transplantation diabetes mellitus (PTDM), which has a major impact on the quality of life, with effects ranging from the control of glycemia times to increased susceptibility to infections and cardiovascular complications. It has been suggested that immunosuppressive therapy, mainly tacrolimus therapy, may be an important factor in the development of PTDM. There is a lack of studies that explore the effects of long-term tacrolimus on PTDM in animal protocols. The objective of this study was therefore to evaluate the effects of long-term therapy with tacrolimus in rats. One group was treated with tacrolimus, injected subcutaneously, in a daily dose of 1 mg/kg of body weight. The chosen dose was sufficient to achieve therapeutic tacrolimus serum levels. The experimental periods were 60, 120, 180 and 240 days. One group was used as control and received daily subcutaneous injections of saline solution during all periods. A tendency towards increased glycemia levels during the initial periods (60 and 120 days) was observed. However, at 180 and 240 days, the glycemia levels were not statistically different from that of the control group of the same period. It may thus be concluded that the deleterious effects of tacrolimus therapy on glycemia may be a time-related side effect.

Microscopic, morphometric and ultrastructural analysis of anastomotic healing in the intestine of normal and diabetic rats

The purpose of this study was to investigate if experimental alloxanic diabetes could cause qualitative changes in intestinal anastomoses of the terminal ileum and distal colon in rats, as compared to controls. 192 male Wistar rats, weighing ± 300g were split into four experimental groups of 48 animals each, after 3 months of follow-up: a control group with ileum anastomoses (G1), a control group with colon anastomoses (G2), a diabetic group with ileum anastomoses (G3) and a diabetic group with colon anastomoses (G4). Animals were evaluated and sacrificed on days 4, 14, 21 and 30 after surgery, and fragments of the small and large intestine where the anastomoses were performed were removed. Samples from 6 animals from each sacrifice moment were submitted to ultrastructural analysis of the collagen fibers using a scanning electron microscope and samples from another 6 animals were submitted to histopathology and optical microscopy studies using picrosirius red-staining. Histopathological analysis of picrosirius red-stained anastomosis slides using an optical microscope at 40x magnification showed that the distribution of collagen fibers was disarranged and also revealed a delay in scar tissue retraction. The morphometric study revealed differences in the collagen filled area for the ileum anastomoses 14 days post surgery whereas, in the case of colon anastomoses, differences were observed at days 4 and 30 post surgery, with higher values in the diabetic animals. Ultrastructure analysis of the ileum and colon anastomoses using a scanning electron microscope revealed fewer wide collagen fibers, the presence of narrower fibers and a disarranged distribution of the collagen fibers. We conclude that diabetes caused qualitative changes in scar tissue as well as in the structural arrangement of collagen fibers, what could explain the reduced wound strength in the anastomosis of diabetic animals. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart.