Razi Journal of Medical Sciences

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Background: Alzheimer's disease (AD) is the most common form of dementia and amyloid peptides playing a central role in its pathogenesis. Recently, regular exercise has been considered as one of the most important non-pharmacological mechanisms to contrast with AD. Therefore, the aim of the present study was to investigate the effect of 4 weeks of exercise preconditioning on the level of soluble amyloid and memory impairment in rats with AD induced by Aβ1-42 injection.
Methods: Eighty four male rats with mean±SD weight of 195±20 g were randomly divided into two groups of aerobic training or resting for 4 weeks. Then, each group was subdivided into 3 subgroups of AD, sham and non-injected. Forty eight hours after the last training session, injection of Aβ1-42 or DMSO into the hippocampus was performed. Seven days after surgery, rats of each groups were either sacrificed (7 rats) or subjected to behavioral testing (7 rats), randomly. Following the collection of blood samples in the victim's rats, the hippocampal tissue was extracted and the levels of Aβ1-42 in plasma and hippocampus, as well as the plasma level of the soluble Low-Density Lipoprotein Receptor-Related Protein-1 (sLRP-1) evaluated.
Results: The results showed that in the exercise + AD group, hippocampal level of Aβ1-42 were lower, and plasma level of Aβ1-42 were higher than the AD group (p<0.001). Plasma sLRP-1 level in the exercise + AD group was also greater than the AD group (p<0.001). Moreover, spatial learning and memory were significantly better in the exercise + AD than AD group (p<0.01).
Conclusion: It seems that 4 weeks of exercise preconditioning could reduce the loss of spatial learning and memory through increasing soluble amyloid beta clearance from the brain.
 

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Background & Aims: Type 2 diabetes is the most common endocrine disorder of the consequences of obesity. Adiponectin, due to its anti-diabetic properties and anti-atherogenic effect, plays an important role in the treatment goals of type 2 diabetic patients and metabolic syndrome. Adiponectin, also called Acrp30, AdipoQ, GBP-28 and APM1, is a 244 amino acid protein that is mainly secreted by adipose tissue. This anti-inflammatory cytokine was simultaneously detected by 4 different groups in different ways. Decreased plasma or serum levels due to some genetic or environmental factors play a significant role in the prevalence of diabetes or insulin resistance syndrome. Unlike other adipokines, such as TNF-α and resistin, which cause insulin resistance in obese or type 2 diabetics, adiponectin expression is reduced in obese and insulin-resistant animal models. A decrease in plasma adiponectin pushes the onset of diabetes in these animal models along with a decrease in insulin sensitivity. Moderate to severe exercise improves serum adiponectin concentrations. After 8 weeks of swimming training by diabetic rats, a significant increase in serum adiponectin levels and its mRNA expression in visceral adipose tissue was observed. Insulin resistance improves adiponectin-independent exercise through exercise. 8 weeks of aerobic training led to increased expression of adiponectin gene and protein in visceral adipose tissue, decreased insulin resistance and blood glucose in obese rats. In another study, 12 weeks of aerobic training increased the expression of adiponectin type 1 and 2 receptors (AdipoR1, AdipoR 2) in blood mononuclear cells along with increased insulin sensitivity and decreased abdominal circumference in young men. This anti-inflammatory cytokine is highly expressed in subcutaneous adipose tissue and affects insulin signaling pathways. Therefore, the present study aimed to determine the effect of 8 weeks of intermittent exercise on adiponectin expression in subcutaneous adipose tissue, insulin resistance, and blood glucose and serum insulin levels.
Methods: The statistical population of the present experimental study consists of all male Wistar rats of Pasteur Institute of Iran, among which 16 10-week-old male rats weighing 210 to 250 g were purchased. The induction of type 2 diabetes was followed by 8 weeks of high-fat diet and intraperitoneal injection of STZ. The rats were divided into interval and control groups. The rats of this group participate in training program from the twentieth week. The control group did not participate in the training program during this period. 48 hours after the last training session, all rats in the periodic and control groups are described after a 10-hour night fast (fasting). 48 hours after the last training session (10 to 12 hours fasting), rats in both groups by intraperitoneal injection of a mixture of ketamine 10% at a dose of 50 mg / kg and xylosine 2% at a dose of 10 mg / kg were anesthetized. The animal's chest was then dissected and a blood sample was taken directly from the animal's heart to ensure minimal animal harm. Subcutaneous adipose tissue was sampled and after washing in physiological serum, it was immersed in 1.8 microtubes containing RNAlaterTM fluid with a ratio of 20% for molecular experiments. Comparison of variables between the two groups was performed using independent t-test. All statistical analyzes were performed using SPSS / Win software version 22.
Results: Results from independent t-test also indicate a significant difference between each of the variables of fasting glucose, serum insulin and insulin resistance between the two groups. In other words, intermittent exercise led to a significant decrease in fasting glucose (P <0.001) and insulin resistance (P = 0.002) and also a significant increase in serum insulin (P <0.001) compared to the control group. However, no significant difference was observed in the expression of adiponectin in subcutaneous adipose tissue. In other words, 8 weeks of intermittent exercise did not affect adiponectin expression in subcutaneous adipose tissue in obese type 2 diabetic rats (P = 0.949).
Conclusion: In the present study, despite no change in adiponectin expression in response to intermittent exercise, glucose levels and insulin resistance decreased significantly. In other words, 8 weeks of intermittent exercise resulted in a significant reduction in glucose and insulin resistance in obese type 2 diabetic rats compared to the control group who did not participate in the exercise program. However, adiponectin expression in subcutaneous adipose tissue was not affected by intermittent exercise. Other studies have attributed lower blood glucose directly to increased insulin function or improved insulin resistance in response to exercise in diabetic rats. Despite the evidence for the effectiveness of exercise on insulin function and glycemic profile in diabetic rats, improvement in insulin resistance was observed in the study of improved insulin function in the absence of adiponectin expression change in subcutaneous adipose tissue. Previous studies, however, have strongly emphasized the potential effect of adiponectin on protein levels or gene expression on insulin signaling pathways in adipose and muscle tissue. In the present study, although the lack of significant change in adiponectin expression in subcutaneous adipose tissue may be attributed to the small number of samples studied or the length of the training period, it is also possible that the effect of periodic exercise on serum adiponectin levels in rats Studies have shown that adiponectin expression in adipose tissue and failure to measure serum adiponectin levels is one of the limitations of the present study. This is because the effects of exercise may affect protein levels or the expression of adiponectin in other tissues of the body, such as muscle or liver tissue. Also, the improvement in insulin resistance in response to intermittent exercise may be attributed to a decrease in inflammatory cytokines. Because increased expression or levels of these proteins in target tissues such as adipose tissue leads to increased insulin resistance. Decreased blood glucose levels may also be rooted in increased serum insulin in response to intermittent exercise. Because independent of changes in insulin at target tissue levels such as adipose and muscle tissue, increasing serum insulin levels in response to exercise leads to lower blood glucose and improved glycemic profile. Since in the present study, the induction of type 2 diabetes in obese rats was due to partial destruction of the pancreas by intraperitoneal injection of low-dose STZ, insulin synthesis and release from pancreatic beta cells was certainly reduced. Therefore, research studies have revealed that continuous exercise through both hyperplasia and hypertrophy of beta cells leads to the repair of these cells, which results in increased synthesis and secretion of insulin from the pancreas and ultimately improve glucose membrane transfer in the target tissue. In this regard, Eizadi et al. (2017) attributed the decrease in blood glucose in response to long-term intermittent exercise in type 2 diabetic rats to increased serum beta and insulin function. It should be noted that in the present study, intermittent exercise was associated with an increase in serum insulin compared to the control group. Interval training is associated with improved fasting glucose in type 2 obese diabetic rats. Despite no change in adiponectin expression in subcutaneous adipose tissue, this improvement may be attributed to increased insulin function or decreased insulin resistance in response to the exercise process. No change in adiponectin expression is reported while dependence of insulin signaling pathways in adipose tissue has been reported in laboratory studies. The lack of significant change in adiponectin expression may be attributed to the small number of samples studied, but further studies in this area are suggested.