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Articles

Endothelial Dysfunction: Cause of the Insulin Resistance Syndrome

  1. Jonathan H Pinkney,
  2. Coen DA Stehouwer,
  3. Simon W Coppack and
  4. John S Yudkin
  1. University College London School of Medicine Centre for Diabetes and Cardiovascular Risk, Whittington Hospital London
  2. Department of Medicine, University of Bristol Bristol, U.K.
  3. Department of Medicine, Academisch Ziekenhuis and Institute for Cardiovascular Research, Vrije Universiteit Amsterdam, The Netherlands
  1. Address correspondence and reprint requests to Dr. Jonathan H. Pinkney, University of Bristol Medical School, Department of Medicine, Southmead Hospital, Bristol BS10 5NB, U.K
Diabetes 1997 Sep; 46(Supplement 2): S9-S13. https://doi.org/10.2337/diab.46.2.S9
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Abstract

Insulin resistance has been proposed as the metabolic basis of atherogenesis. This hypothesis is based on the concept of the “insulin resistance syndrome,” according to which insulin resistance is viewed as the primary abnormality that gives rise to dyslipidemia, essential hypertension, impaired glucose tolerance, and NIDDM. However, this hypothesis takes no account of the wellestablished and central role of vascular endothelium in the atherogenic process. Although endothelial injury is an early and prominent feature of atherogenesis, relatively little attention has been given to its metabolic consequences. In subjects with NIDDM, we have shown that endothelial dysfunction is associated with insulin resistance, raising the question of whether this relationship could be causal. In this article, we review the factors that are considered to be responsible for the development of endothelial dysfunction during atherogenesis, together with the metabolic consequences of endothelial dysfunction. While dysfunction of the endothelium in large and medium-sized arteries plays a central role in atherogenesis, we argue that dysfunction of peripheral vascular endothelium, at arteriolar and capillary level, plays the primary role in the pathogenesis of both insulin resistance and the associated features of the insulin resistance syndrome. We propose that the insulin resistance syndrome, together with many aspects of atherogenesis, can be viewed as the diverse consequences of endothelial dysfunction in different vascular beds. This new and testable hypothesis accounts for both the endothelial and metabolic abnormalities associated with atherogenesis.

  • Accepted December 19, 1996.
  • Copyright © 1997 by the American Diabetes Association

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Endothelial Dysfunction: Cause of the Insulin Resistance Syndrome
Jonathan H Pinkney, Coen DA Stehouwer, Simon W Coppack, John S Yudkin
Diabetes Sep 1997, 46 (Supplement 2) S9-S13; DOI: 10.2337/diab.46.2.S9

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Endothelial Dysfunction: Cause of the Insulin Resistance Syndrome
Jonathan H Pinkney, Coen DA Stehouwer, Simon W Coppack, John S Yudkin
Diabetes Sep 1997, 46 (Supplement 2) S9-S13; DOI: 10.2337/diab.46.2.S9
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