Diabetes induces stromal remodelling and increase in chondroitin sulphate proteoglycans of the rat ventral prostate

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Caracterização de um modelo experimental de neuropatia em ratos diabéticos induzidos pela aloxana

Cem ratos norvégicus, machos, com aproximadamente 3 meses de idade foram distribuídos por sorteio em 2 grupos experimentais: Grupo Controle (GC): com 50 ratos sadios, não diabéticos e Grupo Diabético (GD): com 50 ratos diabéticos, induzidos pela aloxana, sem qualquer tratamento. Cada grupo foi dividido em 5 subgrupos com 10 ratos cada e sacrificados com 1, 3, 6, 9 e 12 meses de seguimento, respectivamente. Parâmetros clínicos (peso, ingestão hídrica e alimentar, e diurese) e laboratoriais (glicemia, glicose urinária e insulina) foram documentados em todos os momentos de avaliação. Um segmento do nervo ciático foi obtido de cada animal, em ambos os grupos, para estudo à MO. e ME. Alterações clínicas e laboratoriais significativas (P<0,01), compatíveis com diabetes grave, foram observadas em todos os animais do GD a partir do 4o dia após a indução. Ratos de ambos os grupos apresentaram alterações no número de fibras mielínicas e nos depósitos intraaxonais de glicogênio que não diferiram, estatisticamente, aos 1, 3 e 6 meses de seguimento. Entretanto, aos 9 e 12 meses, ratos do GD apresentaram diminuição significativa no número de fibras mielínicas, com aumento do número de fibras mielínicas de menor calibre, quando comparados com ratos do GC (P<0,05). Grânulos de glicogênio intraaxonais também foram mais acentuados em ratos do GD no 9o e 12o mês de seguimento. Não foram observadas diferenças na densidade de fibras amielínicas ou alterações ultraestruturais significativas entre os dois grupos, em relação aos espaços intraaxonais e endoneurais, bainhas de mielina e células de Schwann durante todo o estudo.

Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression

We have described previously the prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA-HSP65) in experimental murine tuberculosis. However, the high homology of this protein to the corresponding mammalian 60 kDa heat shock protein (Hsp60), together with the CpG motifs in the plasmid vector, could trigger or exacerbate the development of autoimmune diseases. The non-obese diabetic (NOD) mouse develops insulin-dependent diabetes mellitus (IDDM) spontaneously as a consequence of an autoimmune process that leads to destruction of the insulin-producing beta cells of the pancreas. IDDM is characterized by increased T helper 1 (Th1) cell responses toward several autoantigens, including Hsp60, glutamic acid decarboxylase and insulin. In the present study, we evaluated the potential of DNA-HSP65 injection to modulate diabetes in NOD mice. Our results show that DNA-HSP65 or DNA empty vector had no diabetogenic effect and actually protected NOD mice against the development of severe diabetes. However, this effect was more pronounced in DNA-HSP65-injected mice. The protective effect of DNA-HSP65 injection was associated with a clear shift in the cellular infiltration pattern in the pancreas. This change included reduction of CD4(+) and CD8(+) T cells infiltration, appearance of CD25(+) cells influx and an increased staining for interleukin (IL)-10 in the islets. These results show that DNA-HSP65 can protect NOD mice against diabetes and can therefore be considered in the development of new immunotherapeutic strategies.

Effect of maternal obesity on diabetes development in adult rat offspring

This study aimed to evaluate whether maternal obesity leads to the onset of diabetes in adult Wistar rats offspring. MSG solution neonatally administration induced obesity in rats (F(1)MSG group, n = 30); and saline solution was also administrated to control rats (F1CON group, n = 13). In 3rd month of age, both control and MS G groups were mated for offspring (generation FA named as F2CON, n = 28 and F(2)MSG groups, n = 15; and so both generations were studied until 7th month of life. Lee Index was measured for experimental obesity validation from 5th to 7th month. Glycemia was weekly determined during pregnancy and monthly from 3rd to 7th month. In the end of experimental period all rats were submitted to oral glucose tolerance test (OGTT), with estimation of total area under the curve (AUC); and insulin tolerance test (ITT). Rats were then anesthetized and killed. Data were statistically analyzed with significance level of p < 0.05. Lee Index has confirmed obesity in all MSG rats. Glycemic levels comparisons between generations showed significant maternal interference in control and MSG groups. OGTT analysis showed higher glycemia in obese rats (F(1)MSG) and their offspring (F(2)MSG) as compared to their respective controls; and MSG groups increased AUC from OGTT. As regards ITT, F(2)MSG showed higher glycemia at 30 and 120 min, suggesting a delay of insulin action decreasing. Although glucose intolerance and insulin resistance clinical conditions represent as a factors for type 2 Diabetes mellitus development, this experimental model proposal was not efficient to induce type 2 Diabetes mellitus, but for obesity developing, glucose intolerance and insulin resistance in successive generations of rats. (c) 2007 Elsevier B.V. All rights reserved.

Serum titres of anti-glutamic acid decarboxylase-65 and anti-IA-2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of protein malnutrition on glucose tolerance in rats with alloxan-induced diabetes

Protein-calorie malnutrition produces glucose intolerance and reduced insulin release in response to glucose. Rats adapted to low- or high-protein diets show an increased resistance to the diabetogenic action of a single dose of streptozotocin or alloxan. To determine the effects of dietary protein level on pancreatic function, we measured serum glucose levels under basal conditions and during the oral glucose tolerance test (GTT) performed before and after a single dose of alloxan administered to rats fed a 25% or a 6% protein diet for a period of 8 weeks. The incidence of mild hyperglycemia (serum glucose > 250 mg/dl) was greater among the rats fed the 25% protein diet (81%) than among those fed the 6% protein diet (42%). During the GTT performed before alloxan administration the serum glucose levels of the rats fed the 6% protein diet were not found to be significantly different from those of rats fed the 25% protein diet. During the GTT performed after alloxan injection all rats showed intolerance to the substrate (serum glucose > 160 mg/dl 120 min after glucose administration) regardless of whether basal serum glucose was normal or high. In summary, alloxan was less effective in producing basal hyperglycemia in the rats fed the 6% protein diet than in those fed the 25% protein diet but caused glucose intolerance during the oral GTT in both groups. Thus, it seems that feeding a 6% protein diet to rats offers only partial protection against the toxic effects of alloxan.

Revisão de plantas Brasileiras com comprovado efeito hipoglicemiante no controle do diabetes mellitus

Plants have been used in the cure of diseases from the origins of the humanity. At present, in Brazil, the use is common because of the difficulty of access of part of the population to medical assistance. It is commonly believed that the medicinal plants of traditional use were already tested and ratified by the long-lasting use by the human species, being considered effective medicines, presenting no collateral effects, not needful, therefore, of evaluation. The miraculous self-medication with medicinal plants goes to the point of substituting therapies in serious diseases such as those of hypoglycemic or anti-diabetic effect. For the test of medicinal plants, it is necessary to consider the material quality to be tested, the plant component used, extraction method, dosage, and the experimental species used. Several plants have already had hypoglycemic effects proven experimentally. The objective of this paper was to accomplish a revision of Brazilian medicinal plants, used popularly, as hypoglycemics that had effects proven in animals and in humans.

Moderate physical training increases brain insulin concentrations in experimental diabetic rats

Insulin is an important modulator of growth and metabolic function in the central nervous system. The aim of this study was to investigate the influence of swimming physical training (at 32̈±1̈C, 1 hr/day, 5 days/week, with an overload equivalent to 5% of the body weight, for 4 weeks) on brain insulin concentrations in alloxan induced type 1 diabetic rats. Training attenuated hyperglycemia but had no effect on insulinemia in diabetic rats. Hematocrit and blood albumin values remained without changes. Brain insulin did not change in diabetic rats. However, physical training increased the concentration in both control and diabetic rats. It is concluded that in the present experimental conditions, diabetes had no influence on brain insulin, however moderate physical training increased the hormone in both control and diabetic animals.

Importância do modelo animal para testar hipóteses sobre a fisiopatologia do binômio diabetes e incontinência urinária feminina

Aims: To discuss the importance of studying animal models to test hypotheses about the mechanisms of urinary continence and pathophysiology of diabetes and urinary incontinence. Source of Data: A literature review was conducted in PubMed and SciELO. The key words used were diabetes, urinary incontinence, urethra, human and rats. Summary of Findings: There is a strong relation between the genesis of urinary incontinence and diabetes mellitus. Due to the similarity of normal distribution of skeletal muscle and urethra anatomy between humans and rats, these animal models have been used in current research about these disorders. Conclusions: The use of rats as an animal model is suitable for experimental studies that test hypotheses about the mechanisms of continence and pathophysiology of the binomial diabetes mellitus and urinary incontinence, thus enabling solutions of great value in clinical practice.

Diabetes mellitus triggers oxidative stress in the liver of alloxan-treated rats: A mechanism for diabetic chronic liver disease

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Mild diabetes models and their maternal-fetal repercussions

The presence of diabetes in pregnancy leads to hormonal and metabolic changes making inappropriate intrauterine environment, favoring the onset of maternal and fetal complications. Human studies that explore mechanisms responsible for changes caused by diabetes are limited not only for ethical reasons but also by the many uncontrollable variables. Thus, there is a need to develop appropriate experimental models. The diabetes induced in laboratory animals can be performed by different methods depending on dose, route of administration, and the strain and age of animal used. Many of these studies are carried out in neonatal period or during pregnancy, but the results presented are controversial. So this paper, addresses the review about the different models of mild diabetes induction using streptozotocin in pregnant rats and their repercussions on the maternal and fetal organisms to propose an adequate model for each approached issue. © 2013 D. C. Damasceno et al.

Bacille Calmette-Guérin/DNAhsp65 prime-boost is protective against diabetes in non-obese diabetic mice but not in the streptozotocin model of type 1 diabetes

Type I diabetes is a disease caused by autoimmune destruction of the beta cells in the pancreas that leads to a deficiency in insulin production. The aim of this study was to evaluate the prophylactic potential of a prime-boost strategy involving bacille Calmette-Guérin (BCG) and the pVAXhsp65 vaccine (BCG/DNAhsp65) in diabetes induced by streptozotocin (STZ) in C57BL/6 mice and also in spontaneous type 1 diabetes in non-obese diabetic (NOD) mice. BCG/DNAhsp65 vaccination in NOD mice determined weight gain, protection against hyperglycaemia, decreased islet inflammation, higher levels of cytokine production by the spleen and a reduced number of regulatory T cells in the spleen compared with non-immunized NOD mice. In the STZ model, however, there was no significant difference in the clinical parameters. Although this vaccination strategy did not protect mice in the STZ model, it was very effective in NOD mice. This is the first report demonstrating that a prime-boost strategy could be explored as an immunomodulatory procedure in autoimmune diseases. © 2013 British Society for Immunology.

Proposta de modelo experimental para o estudo da síndrome metabólica

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Caracterização do modelo B6D2F1 para obesidade, diabetes e síndrome metabólica e sua potencialidade para terapia celular em lesão aguda

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)