title: The possible protective role of glucagon-like peptide 1 on endothelium during the meal and evidence for an "endothelial resistance" to glucagon-like peptide 1 in diabetes.
abstract: OBJECTIVE
  Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion. However, GLP-1 also improves endothelial function in diabetes.
  
  
  METHODS
  Sixteen type 2 diabetic patients and 12 control subjects received a meal, an oral glucose tolerance test (OGTT), and two hyperglycemic clamps, with or without GLP-1. The clamps were repeated in diabetic patients after 2 months of strict glycemic control.
  
  
  RESULTS
  During the meal, glycemia, nitrotyrosine, and plasma 8-iso prostaglandin F2α (8-iso-PGF2a) remained unchanged in the control subjects, whereas they increased in diabetic patients. Flow-mediated vasodilation (FMD) decreased in diabetes, whereas GLP-1 increased in both groups. During the OGTT, an increase in glycemia, nitrotyrosine, and 8-iso-PGF2a and a decrease in FMD were observed at 1 h in the control subjects and at 1 and 2 h in the diabetic patients. In the same way, GLP-1 increased in both groups at the same levels of the meal. During the clamps, in both the control subjects and the diabetic patients, a significant increase in nitrotyrosine and 8-iso-PGF2a and a decrease in FMD were observed, effects that were significantly reduced by GLP-1. After improved glycemic control, hyperglycemia during the clamps was less effective in producing oxidative stress and endothelial dysfunction and the GLP-1 administration was most effective in reducing these effects.
  
  
  CONCLUSIONS
  Our data suggest that during the meal GLP-1 can simultaneously exert an incretin effect on insulin secretion and a protective effect on endothelial function, reasonably controlling oxidative stress generation. The ability of GLP-1 in protecting endothelial function seems to depend on the level of glycemia, a phenomenon already described for insulin secretion.
authors.affiliation: Insititut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. aceriell@clinic.ub.es
authors.forename: Antonio
authors.initials: A
authors.lastname: Ceriello
authors.forename: Katherine
authors.initials: K
authors.lastname: Esposito
authors.forename: Roberto
authors.initials: R
authors.lastname: Testa
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bonfigli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marra
authors.forename: Dario
authors.initials: D
authors.lastname: Giugliano
mesh_terms: D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use*; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D008875:Middle Aged; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: C002744:3-nitrotyrosine; D014443:Tyrosine; D052216:Glucagon-Like Peptide 1