Endothelial dysfunction in a model of hyperglycemia and hyperinsulinemia. Pieper, Galen M., Daniel A. Meier, and Steven R. Hager. Department of Transplant Surgery and Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Medical College of Wisconsin, Milwaukee, WI 53226
APStracts 2:0135A, 1995.
Insulinopenic diabetes is known to produce endothelial dysfunction. This dysfunction could arise from either hyperglycemia or inadequate insulin. It is not known whether endothelial dysfunction occurs when hyperglycemia is present with elevated insulin levels. In this study, we utilized an experimental model of hyperglycemia with hyperinsulinemia to investigate latent endothelial dysfunction. Rats were continuously-infused with glucose or saline for 72 hrs to achieve peak plasma glucose concentrations of approximately 25 mM. Plasma insulin rose by 12-fold in glucose-infused rats. No significant differences in serum electrolyte concentration were noted between control and glucose-infused rats after 72 hrs. Blood pressure was not altered by this intervention. Aortic rings taken from control rats relaxed to the endothelium-dependent vasodilators, acetylcholine and A23187, and the endothelium-independent vasodilator, nitroglycerin. Relaxation to acetylcholine but not to A23187 or nitroglycerin was impaired in glucose-infused rat aortic rings. Incubation in vitro with either indomethacin or superoxide dismutase did not restore the impaired relaxation to acetylcholine in rings taken from glucose-infused rats. Thus, hyperglycemia with hyperinsulinemia selectively impairs receptor-dependent, endothelium -dependent relaxation. These studies suggest that elevated glucose may be a common pathway leading to endothelial dysfunction in insulin -dependent diabetes mellitus and hyperglycemia-induced insulin resistance. 

Received 8 September 1993; accepted in final form 15 March 1995.
APS Manuscript Number A801-3.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  4 April 1995.