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Am J Physiol Endocrinol Metab 289: E113-E122, 2005. First published February 22, 2005; doi:10.1152/ajpendo.00594.2004
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Progression of vascular and neural dysfunction in sciatic nerves of Zucker diabetic fatty and Zucker rats

Christine L. Oltman, Lawrence J. Coppey, Jill S. Gellett, Eric P. Davidson, Donald D. Lund, and Mark A. Yorek

Veteran Affairs Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52246

Submitted 16 December 2004 ; accepted in final form 14 February 2005

We have examined the progression of vascular and neural deficits in Zucker rats, Zucker diabetic fatty (ZDF) diabetic rats, and age-matched lean ZDF rats from 8 to 40 wk of age. Both the ZDF diabetic and Zucker rats were glucose intolerant at 8 wk of age. The Zucker rats did not become hyperglycemic but were hyperinsulinemic through 32 wk of age. All ZDF diabetic rats became hyperglycemic by 8 wk of age. Through their life span, serum free fatty acids and triglycerides levels were significantly higher in Zucker and ZDF diabetic rats compared with age-matched lean ZDF rats. After 24 and 28 wk of age, endoneurial blood flow was significantly decreased in ZDF diabetic and Zucker rats. Motor nerve conduction velocity was significantly decreased after 12–14 wk of age in ZDF diabetic rats and at 32 wk of age in Zucker rats. ACh-mediated vascular relaxation of epineurial arterioles of the sciatic nerve was impaired after 8–10 wk of age in ZDF diabetic rats and after ~16 wk of age in Zucker rats. In contrast, vascular relaxation mediated by calcitonin gene-related peptide was impaired significantly after 28 wk of age in ZDF diabetic rats but not impaired in Zucker rats up to 40 wk of age. Markers of oxidative stress were differentially elevated in ZDF diabetic rats and Zucker rats. These data indicate that vascular and neural dysfunction develops in both Zucker and ZDF diabetic rats but at different rates, which may be the result of hyperglycemia.

diabetic neuropathy; vascular reactivity; oxidative stress; superoxide; type 2 diabetes; metabolic syndrome


Address for reprint requests and other correspondence: M. A. Yorek, 3 E 17 Veteran Affairs Medical Center, Iowa City, IA 52246 (e-mail: mark-yorek{at}uiowa.edu)




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