Browsing by Author "Pinto, R."
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- Exercise training decreases proinflammatory profile in Zucker diabetic (type 2) fatty ratsPublication . Teixeira-Lemos, Edite; Reis, F.; Baptista, S.; Pinto, R.; Sepodes, B.; Vala, Helena; Rocha-Pereira, P.; et al.Objective In the present study we evaluated the effect of exercise on the plasma levels of proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and the anti-inflammatory molecule uric acid in the Zucker diabetic fatty (ZDF) rats that are more prone to develop type 2 diabetes mellitus. Methods Sixteen obese ZDF (Gmi fa/fa) rats (8 wk old, 228.40 ± 4.05 g) were randomly assigned to one of two groups (n = 8 each): an exercise-trained group and a sedentary one. In addition, 16 lean ZDF (Gmi +/+) rats (8 wk old, 199.00 ± 3.50 g) were subjected to identical sedentary and exercise conditioning (n = 8 each). Initially, rats swam 15 min/d (5 d/wk) in a 36°C bath. The exercise protocol was gradually increased by 15 min/d until a swimming period of 1 h/d (1 wk) was attained. Thereafter, rats swam 1 h/d, 3 d/wk, for an additional period of 11 wk. Rats were sacrificed 48 h after the last training period and the blood and pancreas were collected. Circulating levels of glucose, glycosylated hemoglobin, total cholesterol, triglycerides, insulin, uric acid, IL-6, and TNF-α were assessed. The concentrations of proinflammatory cytokines in the pancreas were also evaluated. Results In the diabetic ZDF (fa/fa) rats, exercise decreased hyperuricemia (−37.3%) and IL-6 and TNF-α levels (−16.9% and −12.7% respectively) and maintained the weight of the pancreas at near normal. Immunohistochemistry revealed a marked decrease in the expression of TNF-α and IL-6 in the pancreatic islet cells of ZDF (fa/fa) rats. Conclusion These results indicate that aerobic exercise is anti-inflammatory in nature.
- Pancreatic lesions and metabolic aggravation are prevented by low doses of sitagliptin in a rat model of type 2 diabetesPublication . Mega, C.; Vala, Helena; Oliveira, J.; Fernandes, R.; Mascarenhas-Melo, F.; Parada, B.; Pinto, R.; Teixeira, F.; Teixeira de Lemos, E.; Reis, F.Introduction: The management of type 2 diabetes is designed to reduce disease-related complications and improve long-term outcomes. Inhibition of dipeptidyl peptidase-4 (DPP-4) activity by sitagliptin has been shown to improve glycaemic control in patients with type 2 diabetes Mellitus (T2DM) by prolonging the actions of incretin hormones, but the real impact of low-dose sitagliptin treatment on cardiometabolic risk factors and pancreatic lesions is almost unknown. This study aimed to evaluate the effects of low doses of sitagliptin on cardiovascular risk factors and histological pancreas parameters in Zucker Diabetic Fatty rats (ZDF (fa/fa)) an animal model of T2DM. Materials and Methods: Twenty weeks old diabetic obese (fa/fa) ZDF male rats were treated with vehicle or sitagliptin (10 mg/kg BW/day) during 6 weeks (n=8 each). The following parameters were assessed: glycaemia, HbA1c, insulin, lipidic profile; blood pressure. Specimens for pancreatic histopathology were stained with haematoxylin-eosin and periodic-acid-Shiff, examined by light microscopy. Endocrine and exocrine pancreas was evaluated semiquantitatively concerning inflammatory infiltrate, fibrosis, vacuolization and congestion, and scored from 0 (absent) to 3 (severe and extensive damage). Results: Sitagliptin in diabetic obese ZDF rats promoted a positive effect on dysglycaemia, dyslipidaemia and prevented the increase of blood pressure. Endocrine and exocrine pancreas presented a reduction/amelioration of fibrosis severity, inflammatory infiltrate, intra-islet vacuolation, and congestion vs the vehicle-treated diabetic rats. Conclusion: Simultaneous improvement of a sustainable glycaemic profile and of pancreatic histopathological lesions supports the favorable cardiovascular risk profile and may prove beneficial in decreasing long-term complications of T2DM.
- Progression of renal disease in the Zucker Diabetic Fatty rat, an experimental model of Type2 DiabetesPublication . Mega, C.; Vala, Helena; Oliveira, J.; Fernandes, R.; Mascarenhas-Melo, F.; Parada, B.; Pinto, R.; Teixeira, F.; Reis, F.; Teixeira de Lemos, E.
- Renal structure modification in an animal model of type 2 diabetes with aging: focus on hydronephrosisPublication . Mega, C.; Vala, Helena; Oliveira, J.; Fernandes, R.; Mascarenhas-Melo, F.; Parada, B.; Pinto, R.; Teixeira, F.; Teixeira de Lemos, E.; Reis, F.Background and aims: The Zucker Diabetic Fatty (ZDF-fa/fa) rat is one of the most used models for the study of type 2 diabetes (T2DM). Characterization of renal morphology in this model may provide useful insights into the mechanism of diabetic nephropathy progression. The purpose of the present study was to determine renal morphology, identify and characterize renal dysfunction complications such as hydronephrosis, in Zucker Diabetic fatty (ZDF) rat through T2DM evolution. Material and Methods: Male diabetic obese ZDF (fa/fa) rats were sacrificed at 8, 20 and 26 weeks of age and compared with their lean counterparts ZDF (+/+) with de same age. Biochemistry in serum for metabolic assessment was also performed. Kidney slices stained with hematoxylin-eosin and periodic acid-Schiff were evaluated. A semiquantitative rating was assigned for hydronephrosis and scored from 0 (normal) to 3 (severe), based on conformational aspects of the papilla and calyx and cortex compression. Results: A striking progression in the severity of hydronephrosis was observed. All end-disease state rats, 26 weeks of age, showed hydronephrosis, which was more severe in the diabetic rats (scoring: 2, 3) when compared to lean controls (scoring 1). No significant cortical atrophy was found. These abnormalities accompanied aggravation in diabetic desmetabolism. Conclusions: The present study indicates that ZDF rats present nephropathy with hydronephrosis. Lesions are age-related and aggravated by diabetic desmetabolism but don’t hinder morphological evaluation. Therefore the ZDF rat might represent a useful model for the preclinical study of therapeutic interventions in diabetic nephropathy.
- Sitagliptin delays progression of renal lesions in a rodent model of type 2 diabetesPublication . Mega, C.; Vala, Helena; Oliveira, J.; Fernandes, R.; Mascarenhas-Melo, F.; Parada, B.; Pinto, R.; Teixeira, F.; Reis, F.; Lemos, E. T.
- Sitagliptin delays progression of renal lesions in a rodent model of type 2 diabetesPublication . Cristina, M.; Vala, Helena; Oliveira, J.; Fernandes, R.; Mascarenhas-Melo, F.; Parada, B.; Pinto, R.; Teixeira, F.; Reis, F.; Teixeira de Lemos, E.
- Sitagliptin treatment delays the progression of pancreatic and renal lesions and reduces tissular oxidative stress in a type 2 diabetes animal modelPublication . Mega, C.; Vala, Helena; Oliveira, J.; Fernandes, R.; Mascarenhas-Melo, F.; Parada, B.; Pinto, R.; Teixeira, F.; Reis, F.; Lemos, E. T.