Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats

Abstract

We investigated the effects of treadmill exercise performed regularly for 6 weeks on the levels of nerve growth factor (NGF), tyrosine kinase A and p75 receptors, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) 1,2, cyclic AMP response element-binding protein (CREB), and caspase-3 in the soleus of rats with streptozotocin (STZ)-induced diabetes. Thirty-two male Sprague-Dawley rats were divided into the following four groups: (1) normal control group (NCG; n = 8), (2) normal exercise group (NEG; n = 8), (3) diabetes control group (DCG; n = 8), and (4) diabetes exercise group (DEG; n = 8). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg dissolved in 0.05 M citrate buffer, pH 4.5). Rats were subjected to treadmill exercise 5 days a week for 6 weeks. The protein level of NGF significantly increased in the NEG and DEG (p < 0.001), whereas the levels of tyrosine kinase A and p75 receptors significantly increased in the NEG (p < 0.001). The levels of t-PI3-K, p-PI3-K, and p-CREB, and the p-CREB/t-CREB ratio significantly increased in the NEG (p < 0.001, respectively). The p-PI3-K/t-PI3-K ratio significantly increased in the DEG (p < 0.001). The p-Erk1/t-Erk1 ratio significantly increased in the NEG (p < 0.001), whereas the p-Erk2/t-Erk2 ratio significantly decreased in the DCG and DEG (p < 0.001). The caspase-3 level significantly increased in the DCG compared with that in the DEG (p < 0.001). These results suggest that treadmill exercise increases NGF levels and accelerates p-PI3-K activation in order to suppress apoptotic cell death in the soleus muscle of diabetic rats.

Reducing Effects of Aerobic Exercise Training Combined with Berberine Chloride Supplementation on the Apoptotic Markers of Kidney in Streptozotocin-Induced Diabetic Male Rats

“…Rats were acclimatized to the treadmill running at 4 -5 m/minute for 5 -10 minutes over five days. The aerobic exercise training protocol involved in treadmill running for six weeks (3 d/wk, 50% -55% of VO 2 max in diabetic rats) (Table 1) (16,17). The ET program was performed based on loading principle and exercise intensity was 50% -55% of VO 2 max in the last two weeks.…”

Exercise alleviates hypoalgesia and increases the level of calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats

“…These neurotrophic factors promote neuronal survival and differentiation by activating phosphatidylinositol 3-kinase signaling (PI3-K). Moreover, there are various studies demonstrating that treadmill training increases the level of NGF in the sensory neurons (30) and in the hippocampus (31,32) of NT-3 in the spinal cord (33) and of NGF and NT-3 in the soleus muscle (34,35). …”

Molecular Mechanisms of Treadmill Therapy on Neuromuscular Atrophy Induced via Botulinum Toxin A

“…These training effects were more evident in the animals with longer training [50]. In diabetic rats, treadmill running has been shown to increase the level of nerve growth factor in the soleus muscle, and apoptotic cell death was suppressed via accelerating p-PI3-K activation [51]. In summary, the adaptation mechanisms induced via treadmill exercise are multifactorial with cellular changes inside the muscle fibers as well as changes in peripheral and central nervous systems.…”