Effect of voluntary exercise on intracellular signalling pathways of angiogenesis in the sciatic nerve of type 1 diabetic castrated male rats

Abstract

Objectives Impaired angiogenesis in sciatic nerve is a major complication of diabetic neuropathy. Protein kinase B (AKT) and extracellular signal regulated kinase (ERK) signaling pathways play critical roles during capillary-like network formation in the angiogenesis process. Methods Twenty-four adult male Wistar rats (weight: 250–300 g) were used in the research. The rats were randomly divided into four groups (n = 6): (1) diabetic (Dia), (2) diabetic + castration (Dia-Cas), (3) diabetic + exercise (Dia-E), and (4) diabetic + castration + exercise (Dia-Cas-E). Type 1 diabetes (T1D) was induced with streptozotocin (50 mg/kg). After 6 weeks, sciatic nerve was separated and used for histological evaluation and determination of phosphorylated AKT (P-AKT) and phosphorylated ERK (P-ERK) levels by ELISA method. Results Glucose levels decreased in the Dia-E group compared to the Dia-Cas group (p < 0.01). In addition, our finding shows that exercise in the Dia-Cas group diminished blood glucose levels compared to the Dia-Cas group but this effect of exercise was not significant. Voluntary exercise in the diabetic castrated group decreased P-AKT protein and increased P-ERK 1/2 protein levels in the sciatic tissue compared to the diabetes group significantly (p < 0.05). Histopathological findings showed that Dia-Cas group with 6-week exercise training significantly raised the number of microvascular density in the sciatic tissue of diabetic rats compared to the diabetic group (p < 0.05). Conclusions Voluntary exercise in diabetic rats increases angiogenesis in the sciatic nerve. The possible mechanism is the increase of P-ERK 1/2 but not P-AKT levels in the sciatic nerve of T1D rats.