Vitamin C Further Improves the Protective Effect of Glucagon-like Peptide-1 on Acute Hypoglycemia-Induced Oxidative Stress, Inflammation, and Endothelial Dysfunction in Type 1 Diabetes

  1. Stefano Genovese, MD3
  1. 1Diabetes and Endocrinology, Insititut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
  2. 2Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Hospital Clínic Barcelona, Barcelona, Spain
  3. 3Department of Cardiovascular and Metabolic Diseases, Istituto di Ricovero e Cura a Carattere Scientifico Gruppo Multimedica, Sesto San Giovanni (MI), Italy
  1. Corresponding author: Antonio Ceriello, aceriell{at}clinic.ub.es.

Abstract

OBJECTIVE To test the hypothesis that acute hypoglycemia induces endothelial dysfunction and inflammation through the generation of an oxidative stress. Moreover, to test if the antioxidant vitamin C can further improve the protective effects of glucagon-like peptide 1 (GLP-1) on endothelial dysfunction and inflammation during hypoglycemia in type 1diabetes.

RESEARCH DESIGN AND METHODS A total of 20 type 1 diabetic patients underwent four experiments: a period of 2 h of acute hypoglycemia with or without infusion of GLP-1 or vitamin C or both. At baseline, after 1 and 2 h, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2a (PGF2a), soluble intracellular adhesion molecule-1a (sICAM-1a), interleukin-6 (IL-6), and flow-mediated vasodilation were measured. At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced.

RESULTS At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced.

CONCLUSIONS This study shows that vitamin C infusion, during induced acute hypoglycemia, reduces the generation of oxidative stress and inflammation, improving endothelial dysfunction, in type 1 diabetes. Furthermore, the data support a protective effect of GLP-1 during acute hypoglycemia, but also suggest the presence of an endothelial resistance to the action of GLP-1, reasonably mediated by oxidative stress.

  • Received March 29, 2013.
  • Accepted July 24, 2013.

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This Article

  1. Diabetes Care
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