Cerebellar Insulin/IGF-1 signaling in diabetic rats: Effects of exercise training

Abstract

The Diabetes Mellitus (DM) is a chronic disease associated with loss of brain regions such as the cerebellum, increasing the risk of developing neurodegenerative diseases such as Parkinson's disease (PD). In the brain of diabetic and PD organisms the insulin/IGF-1 signaling is altered. Exercise training is an effective intervention for the prevention of neurodegerative diseases since it release neurotrophic factors and regulating insulin/IGF-1 signaling in the brain. This study aimed to evaluate the proteins involved in the insulin/IGF-1 pathway in the cerebellum of diabetic rats subjected to exercise training protocol. Wistar rats were distributed in four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). Diabetes was induced by Alloxan (ALX) (32mg/kgb.w.). The training program consisted in swimming 5days/week, 1h/day, during 6 weeks, supporting an overload corresponding to 90% of the anaerobic threshold. At the end, cerebellum was extracted to determinate the protein expression of GSK-3β, IRβ and IGF-1R and the phosphorylation of β-amyloid, Tau, ERK1+ERK2 by Western Blot analysis. All dependent variables were analyzed by one-way analysis of variance with significance level of 5%. Diabetes causes hyperglycemia in both diabetic groups; however, in TD, there was a reduction in hyperglycemia compared to SD. Diabetes increased Tau and β-amyloid phosphorylation in both SD and TD groups. Furthermore, aerobic exercise increased ERK1+ERK2 expression in TC. The data showed that in cerebellum of diabetic rats induced by alloxan there are some proteins expression like Parkinson cerebellum increased, and the exercise training was not able to modulate the expression of these proteins.

The Effect of Endurance Training on Apoptotic Inducing Factor (AIF) in Cerebellum of Type 1 Diabetic Rats

“…Although the training protocol improved the blood glucose in diabetic animals, it did not able to return blood glucose to normal level. These results reflect the chronic adaptations induced by exercise training in diabetic patients that has been reported in previous study (18). Apoptosis confirmed by detection of increased AIF proteins in cerebellum of diabetic rats.…”

“…Although endurance training had beneficial effects against diabetes induced apoptosis in cerebellum, it could not return the levels of studied factors to normal values, confirming that exercise can only use as a complementary approach to attenuate the adverse effects of hyperglycemia in cerebellum. Based on our knowledge data on cerebellar changes at molecular levels in diabetic condition are more limited and less studied (18,20). Previous works have confirmed the presence of mitochondrial dysfunction and oxidative stress in different regions of brain in diabetic animal model that can trigger the apoptosis and cell death.…”

“…In addition, in diabetic conditions, hyperglycemic stress causes oxidative damage to mitochondria, which may lead to apoptosis and cell death (16,17). However, few studies have explained the alteration of cerebellar cellular mechanisms following aerobic exercise (18,19). So far, little is known about the protective effect of endurance exercise on the apoptosis process in the cerebellum of diabetic rats.…”

Cerebellar Synaptopathy in Streptozotocin-Induced Diabetic Rats

“…The generation of excessive free radicals contributed to increased neuronal death by the oxidisation of proteins, damaging of DNA, and activation of the cellular membrane lipid peroxidation (Matough et al, 2012). Since insulin and insulin growth factors transmitted signal downstream to regulate neuronal survival (Duarte et al), a reduction in these growth factors and their receptors was reported in the cerebellum of diabetic animals (Borges et al, 2017) and may be another possible mechanism of diabetes-induced neuronal cell death. These mechanisms are the cause of the Purkinje cell death and the decrease in numbers in the cerebellum of diabetic rat, as shown in the present study.…”

Effect of Endurance Training on Cerebellar Gene Expression of the ADP-Ribosylation Factor 6 in Rats with Diabetic Peripheral Neuropathy

“…Two days after the last exercise session in the 6th week of training, rats (N = 6 in each group) were anesthetized by inhalation of 2% halothane in a mixture of 20% O 2 , 80% CO 2 (10), and their cerebellar tissue was removed under sterile conditions and immediately perfused in 4% paraformaldehyde (11).…”