Effect of treatment of diabetic rats with dehydroepiandrosterone on vascular and neural function.
Nutritional supplementation with dehydroepiandrosterone (DHEA) may be a candidate for treating diabetes-induced vascular and neural dysfunction. DHEA is a naturally occurring adrenal androgen that has antioxidant properties and is reportedly reduced in diabetes. Using a prevention protocol, we found that dietary supplementation of streptozotocin-induced diabetic rats with 0.1, 0.25, or 0.5% DHEA caused a concentration-dependent prevention in the development of motor nerve conduction velocity and endoneurial blood flow impairment, which are decreased in diabetes. At 0.25%, DHEA significantly prevented the diabetes-induced increase in serum thiobarbituric acid-reactive substances and sciatic nerve conjugated diene levels. This treatment also reduced the production of superoxide by epineurial arterioles of the sciatic nerve. DHEA treatment (0.25%) significantly improved vascular relaxation mediated by acetylcholine in epineurial vessels of diabetic rats. Sciatic nerve Na+-K+-ATPase activity and myoinositol content was also improved by DHEA treatment, whereas sorbitol and fructose content remained elevated. These studies suggest that DHEA, by preventing oxidative stress and perhaps improving sciatic nerve Na+-K+-ATPase activity, may improve vascular and neural dysfunction in diabetes.
Yorek
Mark A
MA
Veterans Affairs Medical Center, Diabetes Endocrinology Research Center, and Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52246, USA. myorek@icva.gov
Coppey
Lawrence J
LJ
Gellett
Jill S
JS
Davidson
Eric P
EP
Bing
Xinyu
X
Lund
Donald D
DD
Dillon
Joseph S
JS
D000276:Adjuvants, Immunologic / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000097:blood / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004967:Estrogens / Q000097:blood; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D010525:Peripheral Nerves / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D001786:Blood Glucose; D004967:Estrogens; D013481:Superoxides; D003687:Dehydroepiandrosterone