Ricardo José Gomes

Spatial memory in sedentary and trained diabetic rats: Molecular mechanisms

Diabetes mellitus is a chronic disease that has been associated with memory loss, neurological disorders, and Alzheimers disease. Some studies show the importance of physical exercise to prevent and minimize various neurological disorders. It is believed that the positive effects of exercise on brain functions are mediated by brain insulin and insulin‐like growth factor‐1 (IGF‐1) signaling. In this study, we investigate the role of swimming exercise training on hippocampus proteins related to insulin/IGF‐1 signaling pathway in Type 1 diabetic rats and its effects on spatial memory. Wistar rats were divided into four groups namely sedentary control, trained control, sedentary diabetic (SD), and trained diabetic (TD). Diabetes was induced by Alloxan (ALX) (32 mg/kg b.w.). The training program consisted in swimming 5 days/week, 1 h/day, per 6 weeks, supporting an overload corresponding to 90% of the anaerobic threshold. We employed ALX‐induced diabetic rats to explore learning and memory abilities using Morris water maze test. At the end of the training period, the rats were sacrificed 48 h after their last exercise bout when blood samples were collected for serum glucose, insulin, and IGF‐1 determinations. Hippocampus was extracted to determinate protein expression (IR, IGF‐1R, and APP) and phosphorylation (AKT‐1, AKT‐2, Tau, and β‐amyloide proteins) by Western Blot analysis. All dependent variables were analyzed by two‐way analysis of variance with significance level of 5%. Diabetes resulted in hyperglycemia and hypoinsulinemia in both SD and TD groups (P < 0.05); however, in the training‐induced group, there was a reduction in blood glucose in TD. The average frequency in finding the platform decreased in SD rats; however, exercise training improved this parameter in TD rats. Aerobic exercise decreased Tau phosphorylation and APP expression, and increased some proteins related to insulin/IGF‐1 pathway in hippocampus of diabetic rats. Thus, these molecular adaptations from exercise training might contribute to improved spatial learning and memory in diabetic organisms.

Morphology and protein content of hepatocytes in type I diabetic rats submitted to physical exercises

The importance of physical exercise practice in the treatment of diabetes has been reported in many studies recently, but only limited data can be found regarding its benefits on liver morphology and protein content of hepatocytes. In order to assess the changes arising from the development of type I diabetes and the benefits of a training protocol, Wistar rats were divided into four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). The training protocol consisted of swimming for 60 min a day, 5 days/week, during 8 weeks. Liver samples were collected, processed and analyzed by histochemical and ultrastructural techniques. Biochemical tests were also conducted to examine the protein content and quantity of DNA in the liver. In morphological assessment, the presence of areas of cytoplasmic basophilia observed in control subjects was not visualized in sedentary diabetics. It was related to differences in the amount of mitochondria in the cytosol. The mitochondrial structure has not undergone relevant changes, and the number of rough endoplasmic reticulum cisterns was clearly inferior in sedentary diabetics, suggesting lower protein production. However, the biochemical analysis of protein content indicated no statistical differences between groups. The exercise, in turn, was not responsible for major changes in these characteristics. On the whole, the morphological damages arising from type I diabetes were noteworthy. Nevertheless, regular physical training was not responsible for significant improvements in some respects, making evident the need for combined application of a distinct form of treatment.

Regulation of hepatic TRB3/Akt interaction induced by physical exercise and its effect on the hepatic glucose production in an insulin resistance state.

To maintain euglycemia in healthy organisms, hepatic glucose production is increased during fasting and decreased during the postprandial period. This whole process is supported by insulin levels. These responses are associated with the insulin signaling pathway and the reduction in the activity of key gluconeogenic enzymes, resulting in a decrease of hepatic glucose production. On the other hand, defects in the liver insulin signaling pathway might promote inadequate suppression of gluconeogenesis, leading to hyperglycemia during fasting and after meals. The hepatocyte nuclear factor 4, the transcription cofactor PGC1-α, and the transcription factor Foxo1 have fundamental roles in regulating gluconeogenesis. The loss of insulin action is associated with the production of pro-inflammatory biomolecules in obesity conditions. Among the molecular mechanisms involved, we emphasize in this review the participation of TRB3 protein (a mammalian homolog of Drosophila tribbles), which is able to inhibit Akt activity and, thereby, maintain Foxo1 activity in the nucleus of hepatocytes, inducing hyperglycemia. In contrast, physical exercise has been shown as an important tool to reduce insulin resistance in the liver by reducing the inflammatory process, including the inhibition of TRB3 and, therefore, suppressing gluconeogenesis. The understanding of these new mechanisms by which physical exercise regulates glucose homeostasis has critical importance for the understanding and prevention of diabetes.

Resistance Training Promotes Reduction in Blood Pressure and IncreasePlasma Adiponectin of Hypertensive Elderly Patients

Introduction: Hypertension is the most common disease in industrialized countries, and it is responsible for the major risk factor for developing cardiovascular diseases. Aging increases the prevalence of hypertension and the loss of muscle mass. The aim of the present study was to evaluate the effect of resistance training on blood pressure and inflammatory markers in hypertensive elderly. Methods: One hundred thirty-five hypertensive elderly were distributed into two groups: training (TG, n=86), and control (CG, n=49). TG underwent 16 weeks of resistance training with three sets of 12 repetitions in eight exercises (50% of one maximal repetition) and the CG remained sedentary. Twenty-four-hour ambulatory blood pressure was recorded. Results: Resistance training increased muscle strength (21.10 ± 0.71 vs. 25.76 ± 0.80 kg [p<0.01] chest press; 9.93 ± 0.29 vs. 14.41 ± 0.45 kg [p<0.01] knee extension), as well as reduced systolic blood pressure (126.79 ± 1.29 vs. 124.32 ± 1.37 mmHg [p<0.05] daytime; 125.11 ± 1.28 vs. 122.50 ± 1.38 mmHg [p<0.05] 24-h period) in TG. In addition, resistance training increased the circulating levels of adiponectin (4.61 ± 0.24 vs. 5.32 ± 0.25 pg/mL [p<0.01]) and reduced the circulating levels of ICAM-1 (334.38 ± 10.89 vs. 293.05 ± 9.78 pg/mL [p<0.01]). Conclusion: Our results suggest that resistance training is an important tool to reduce blood pressure and improve muscle strength in hypertensive elderly. Besides that, resistance training increase circulating levels of adiponectin, and reduce the levels of plasma ICAM-1 in hypertensive elderly.

Histochemical and ultrastructural analysis of hepatic glycogen and collagen fibers in alloxan-induced diabetic rats submitted to long-term physical training

Alterations in liver functions are common among diabetic patients, and many symptoms in the liver have been reported, including changes in glycogen stores and in the amount of collagen fibers. The practice of physical training and its morphological effects in this organ, however, are scarcely studied. In order to observe the morphological effects of alloxan-induced diabetes and the alterations arising from the practice of long-term chronic physical training in the liver, samples were collected and processed, and then analyzed by means of the histochemical techniques Periodic Acid-Schiff and Picrosirius-Hematoxylin, and ultrastructural cytochemical test of Afzelius. Through evaluation of the tissue, it was observed a drastic reduction in hepatic glycogen stores of sedentary diabetics, recovered in trained diabetic rats. Furthermore, it was detected a decrease in the content of perisinusoidal collagen fibers in the diabetic liver, also recovered due to the development of a training protocol. On ultrastructural level, cytochemical analysis confirmed the loss of glycogen and the recovery obtained by training. In conclusion, the practice of a long-term chronic physical training protocol may be considered an important assistant in the treatment of diabetes, mitigating the occurrence of possible damages to liver tissue.

Comparative Effects of Physical Training and Metformin in Diabetic Rats

Diabetes mellitus is a metabolic disease associated with multiple organ damage, dysfunction and failure. Met- formin is widely used to treat diabetes, but regular exercise also improves metabolic control in diabetic individuals and has an important role in the management of this disease. In this work, we compared the effects of metformin and physical training in diabetic male Wistar rats. Four groups of rats were used: (n=6 per group): sedentary control (SC), sedentary diabetic (SD), trained diabetic (DT) and metformin diabetic (MD). Diabetes was induced with alloxan (30 mg/kg, b.w.). The physical training protocol consisted of a 1 h swimming session/day, five days/week for eight weeks with a load corre- sponding to 5% of the body weight. Metformin treatment consisted in 1.4 mg/ml per day, administered in the drinking wa- ter. At the end of the experimental period, the rats were sacrificed and blood was collected to measure serum glucose, in- sulin and albumin. Glycogen was quantified in gastrocnemius muscle, liver and heart, the protein/DNA ratio was men- sured in liver and heart triglycerides was also measured in the heart. Diabetes reduced the serum insulin and liver glyco- gen levels and the protein/DNA ratio, but increased the serum glucose and heart glycogen levels; there were no significant variations in serum albumin levels. Physical training increased the muscle glycogen level. Physical training and met- formin were equally effective in reducing the serum glucose concentration and in restoring the hepatic and cardiac glyco- gen stores and the hepatic protein/DNA ratio in diabetic rats. These results show that chronic exercise was as effective as metformin in improving the metabolic profile of diabetic rats and in preventing diabetes-induced alterations.

Hepatic Steatosis Markers in Diabetic Rats Trained at the Aerobic/ Anaerobic Transition

Aims: To analyze the effects of exercise performed at the aerobic/anaerobic transition (Lan) on Non-Alcoholic Hepatic Steatosis (NAHS) markers in type 1 diabetic rats. Methods: Adult Wistar rats were separated into four groups: Sedentary Control (SC), Trained Control (TC), Sedentary Diabetic (SD) and Trained Diabetic (TD). The trained groups swam supporting workloads equivalent to the Lan for one hour/day, five days/week, for eight weeks. Body weight, serum albumin concentrations, glucose concentrations, Free Fatty Acid (FFA) concentrations, NAHS markers (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) and total lipid concentrations in the liver were analyzed. Results: The diabetic groups showed higher serum glucose concentrations and more weight loss compared to the controls, although the TD group was less affected than the SD group. Training resulted in a decrease in serum glucose levels in the diabetic rats. The NAHS markers, total lipid concentrations in the liver and serum albumin concentrations did not differ between the groups. However, the diabetic animals had higher serum FFA levels than the controls. Conclusion: Physical training at Lan attenuates weight loss and improves serum glucose homeostasis in diabetic animals. In addition, serum ALT and AST enzymes proved to be adequate markers of lipid levels in the livers in this animal model.

Impaired insulin signaling and spatial learning in middle-aged rats: The role of PTP1B

Abstract The insulin and Brain‐Derived Neurotrophic Factor (BDNF) signaling in the hippocampus promotes synaptic plasticity and memory formation. On the other hand, aging is related to the cognitive decline and is the main risk factor for Alzheimers Disease (AD). The Protein‐Tyrosine Phosphatase 1B (PTP1B) is related to several deleterious processes in neurons and emerges as a promising target for new therapies. In this context, our study aims to investigate the age‐related changes in PTP1B content, insulin signaling, &bgr;‐amyloid content, and Tau phosphorylation in the hippocampus of middle‐aged rats. Young (3 months) and middle‐aged (17 months) Wistar rats were submitted to Morris‐water maze (MWM) test, insulin tolerance test, and molecular analysis in the hippocampus. Aging resulted in increased body weight, and insulin resistance and decreases learning process in MWM. Interestingly, the middle‐aged rats have higher levels of PTP‐1B, lower phosphorylation of IRS‐1, Akt, GSK3&bgr;, mTOR, and TrkB. Also, the aging process increased Tau phosphorylation and &bgr;‐amyloid content in the hippocampus region. In summary, this study provides new evidence that aging‐related PTP1B increasing, contributing to insulin resistance and the onset of the AD. HighlightsMiddle‐aging is associated with increased PTP1B content in the hippocampus.The PTP1B is one of the major tyrosine phosphatases of IR, IRS1, and TrkB.This process disrupts the hippocampal insulin signaling, impairing the spatial learning.

Undulatory physical resistance training program increases maximal strength in elderly type 2 diabetics

Objective To investigate the effects of a specific protocol of undulatory physical resistance training on maximal strength gains in elderly type 2 diabetics. Methods The study included 48 subjects, aged between 60 and 85 years, of both genders. They were divided into two groups: Untrained Diabetic Elderly (n=19) with those who were not subjected to physical training and Trained Diabetic Elderly (n=29), with those who were subjected to undulatory physical resistance training. The participants were evaluated with several types of resistance training’s equipment before and after training protocol, by test of one maximal repetition. The subjects were trained on undulatory resistance three times per week for a period of 16 weeks. The overload used in undulatory resistance training was equivalent to 50% of one maximal repetition and 70% of one maximal repetition, alternating weekly. Statistical analysis revealed significant differences (p<0.05) between pre-test and post-test over a period of 16 weeks. Results The average gains in strength were 43.20% (knee extension), 65.00% (knee flexion), 27.80% (supine sitting machine), 31.00% (rowing sitting), 43.90% (biceps pulley), and 21.10% (triceps pulley). Conclusion Undulatory resistance training used with weekly different overloads was effective to provide significant gains in maximum strength in elderly type 2 diabetic individuals.

Morphological analysis of colon goblet cells and submucosa in type I diabetic rats submitted to physical training

Colon layers, especially the submucosa, as well as the secretion of goblet cells are extremely important for the functioning and transit of substances in this organ. However, the damages arising from type I diabetes and the effects of physical training, which plays crucial role in the treatment of this disease, are not yet known in these regions. To analyze the changes in colon submucosa and goblet cells of diabetic rats, as well as the effects of physical training, Wistar rats were divided into four groups: sedentary control, trained control, sedentary diabetic (SD), and trained diabetic (TD). The training protocol consisted of swimming for 60 min a day, 5 days per week, during 8 weeks. Colon samples were collected, processed, and evaluated by histochemical and ultrastructural techniques. Goblet and submucosa cells did not show alterations in shape, size, protein and carbohydrate content, in all treatment groups. Decreased amount of collagen fibers, however, was observed in the submucosa and lamina propria of SD rats, but this alteration was recovered in TDs. The ultrastructural analysis, in turn, revealed greater quantity of Golgi apparatus cisterns in SDs, distinctly than TDs, which showed improvement in this diabetic condition. Thus, physical training was responsible for the recovery of some important diabetic alterations, possibly improving the motility of substances in the large intestine. Nevertheless, it cannot be considered alone in the treatment of this disease, requiring the combined practice of other methods. Microsc. Res. Tech. 75:821–828, 2012.