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Diabetes and Cholesterol Metabolism

The succinate hypothesis

  1. Norman H. Ertel, MD, FACP
  1. From the Medical Service, VA New Jersey Health Care System and the Department of Medicine, the University of Medicine and Dentistry, New Jersey Medical School, Newark, New Jersey

    In the recent article by Simonen et al. (1) demonstrating increased cholesterol synthesis in obese patients with diabetes, the authors did not consider a possible mechanism suggested by the “succinate hypothesis,” which is elegantly summarized by Fahien and MacDonald (2) in a separate article. Fahien and MacDonald showed that succinate esters are potent insulin secretagogues (almost as potent as glucose) through generation of succinyl-CoA (S-CoA). This seemed to …

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