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

  1. Dario Giugliano, MD2
  1. 1Insititut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
  2. 2Division of Metabolic Diseases, Center of Excellence for Cardiovascular Diseases, Second University of Naples, Naples, Italy
  3. 3Metabolic and Nutrition Research Centre on Diabetes, INRCA, Ancona, Italy
  1. Corresponding author: Antonio Ceriello, aceriell{at}clinic.ub.es.

Abstract

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.

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This Article

  1. Diabetes Care
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