title: 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.
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 1 diabetes.
  
  
  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.
authors.affiliation: Corresponding author: Antonio Ceriello, aceriell@clinic.ub.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ceriello
authors.forename: Anna
authors.initials: A
authors.lastname: Novials
authors.forename: Emilio
authors.initials: E
authors.lastname: Ortega
authors.forename: Silvia
authors.initials: S
authors.lastname: Canivell
authors.forename: Lucia
authors.initials: L
authors.lastname: La Sala
authors.forename: Gemma
authors.initials: G
authors.lastname: Pujadas
authors.forename: Loredana
authors.initials: L
authors.lastname: Bucciarelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rondinelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Genovese
mesh_terms: D000208:Acute Disease; D000975:Antioxidants / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000008:administration & dosage*; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D054795:Incretins / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood / Q000517:prevention & control*; D007262:Infusions, Intravenous; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D055815:Young Adult
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D001205:Ascorbic Acid