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
- Antonio Ceriello, MD1,
- Katherine Esposito, MD2,
- Roberto Testa, MD3,
- Anna Rita Bonfigli, PHD3,
- Maurizio Marra, PHD3 and
- Dario Giugliano, MD2
- 1Insititut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
- 2Division of Metabolic Diseases, Center of Excellence for Cardiovascular Diseases, Second University of Naples, Naples, Italy
- 3Metabolic and Nutrition Research Centre on Diabetes, INRCA, Ancona, Italy
- Corresponding author: Antonio Ceriello, .
OBJECTIVE Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion. However, GLP-1 also improves endothelial function in diabetes.
RESEARCH DESIGN AND METHODS Sixteen type 2 diabetic patients and 12 control patients 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 F2alpha (8-iso-PGF2a) remained unchanged in the control patients, 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 patients 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 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.
- Received October 14, 2010.
- Accepted December 21, 2010.
- © 2011 by the American Diabetes Association.
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