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.

RESEARCH DESIGN AND 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: Antonio Ceriello, Katherine Esposito, Roberto Testa, Anna Rita Bonfigli, Maurizio Marra, Dario Giugliano
• Journal: Diabetes care (Diabetes Care) Vol. 34 Issue 3 Pg. 697-702 (Mar 2011) ISSN: 1935-5548 [Electronic] United States
• PMID: 21273492 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• 3-nitrotyrosine
• Tyrosine
• Glucagon-Like Peptide 1

Topics

• Diabetes Mellitus (drug therapy, metabolism)
• Endothelium, Vascular (drug effects)
• Female
• Glucagon-Like Peptide 1 (therapeutic use)
• Glucose Tolerance Test
• Humans
• Male
• Middle Aged
• Tyrosine (analogs & derivatives, metabolism)
• Vasodilation (drug effects)