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

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Abstract:

Abstract Aim: 

Addition of dehydroepiandrosterone (DHEA) to a cultured skeletal muscle locally synthesizes 5α-dihydrotestosterone (DHT). It induced activation of glucose metabolism-related signalling pathway via protein kinase B (Akt) and protein kinase C zeta/lambda (PKC ζ/λ)-glucose transporter-4 (GLUT4) proteins. However, such an effect of DHEA in vivo remains unclear. Methods: 

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). Results: 

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 ζ/λ, and phosphofructokinase and hexokinase enzyme activities increased significantly by DHEA injection. However, DHEA-induced improvements in Akt and PKC ζ/λ-GLUT4 pathways were blocked by a DHT inhibitor. Conclusion: 

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 ζ/λ-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.

Keywords: dehydroepiandrosterone; glucose transporter-4; protein kinase B; protein kinase C ζ/λ

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1748-1716.2009.02011.x

Affiliations: 1:  Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan 2:  Department of Physical Education, International Pacific University, Okayama City, Okayama, Japan 3:  Center for Disease Biology and Integrative Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

Publication date: November 1, 2009

bsc/aps/2009/00000197/00000003/art00005
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