DHEA improves impaired activation of Akt and PKC ζ/λ‐GLUT4 pathway in skeletal muscle and improves hyperglycaemia in streptozotocin‐induced diabetes rats

Abstract

Addition of dehydroepiandrosterone (DHEA) to a cultured skeletal muscle locally synthesizes 5alpha-dihydrotestosterone (DHT). It induced activation of glucose metabolism-related signalling pathway via protein kinase B (Akt) and protein kinase C zeta/lambda (PKC zeta/lambda)-glucose transporter-4 (GLUT4) proteins. However, such an effect of DHEA in vivo remains unclear. Using streptozotocin (STZ)-induced rats with type 1 diabetes mellitus, we tested the hypothesis that a single bout of DHEA injection in the rats improves hyperglycaemia and muscle GLUT4-regulated signalling pathway. After 1 week of STZ injection (55 mg kg(-1)) with male Wistar rats, fasting glucose concentrations were determined in a blood sample taken from the tail vein. Blood glucose levels were then monitored for 180 min after DHEA or sesame oil (control) was injected (n = 10 for each group). Blood glucose levels decreased significantly for 30-150 min after 2 mg DHEA injection in the STZ rats. In the skeletal muscle, expression and translocation of GLUT4 protein, phosphorylation of Akt and PKC zeta/lambda, and phosphofructokinase and hexokinase enzyme activities increased significantly by DHEA injection. However, DHEA-induced improvements in Akt and PKC zeta/lambda-GLUT4 pathways were blocked by a DHT inhibitor. These results suggest that a single bout of DHEA injection can improve hyperglycaemia and activate the glucose metabolism-related signalling pathway via Akt and PKC zeta/lambda-GLUT4 proteins of skeletal muscles in rats. Moreover, these results show that a DHEA-induced increase in muscle glucose uptake and utilization might contribute to improvement in hyperglycaemia in type 1 diabetes mellitus.