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1 Department of Internal Medicine, Veterans Affairs Medical Center, Iowa City, Iowa, USA
* To whom correspondence should be addressed. E-mail: mark-yorek{at}uiowa.edu.
We have examined the progression of vascular and neural deficits in Zucker rats, ZDF diabetic rats and age-matched lean ZDF rats from 8-40 weeks of age. Both the ZDF diabetic and Zucker rats were glucose intolerant at 8 weeks of age. The Zucker rats did not become hyperglycemic but were hyperinsulinemic through 32 weeks of age. All ZDF diabetic rats became hyperglycemic by 8 weeks of age. Through their life span serum free fatty acids and triglycerides levels were significantly higher in Zucker and ZDF diabetic rats compared to age-matched lean ZDF rats. After 24 to 28 weeks of age endoneurial blood flow was significantly decreased in ZDF diabetic and Zucker rats. Motor nerve conduction velocity was significantly decreased after 12-14 weeks of age in ZDF diabetic rats and at 32 weeks of age in Zucker rats. Acetylcholine-mediated vascular relaxation of epineurial arterioles of the sciatic nerve was impaired after 8-10 weeks of age in ZDF diabetic rats and after about 16 weeks of age in Zucker rats. In contrast, vascular relaxation mediated by calcitonin gene-related peptide was impaired significantly after 28 weeks of age in ZDF diabetic rats but not impaired in Zucker rats up to 40 weeks 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 due to hyperglycemia.
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