Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease.

Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901226 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0193-1849 (Print) Linking ISSN: 01931849 NLM ISO Abbreviation: Am J Physiol Endocrinol Metab Subsets: MEDLINE

Original Publication: Bethesda, MD. : American Physiological Society

Coronary Disease/*drug therapy ; Coronary Disease/*physiopathology ; Diabetes Mellitus, Type 2/*complications ; Diabetic Angiopathies/*drug therapy ; Diabetic Angiopathies/*physiopathology ; Endothelium, Vascular/*physiopathology ; Glucagon/*therapeutic use ; Peptide Fragments/*therapeutic use ; Protein Precursors/*therapeutic use; Adult ; Brachial Artery/drug effects ; Brachial Artery/physiopathology ; Coronary Circulation ; Coronary Disease/etiology ; Coronary Vessels/metabolism ; Cross-Over Studies ; Diabetic Angiopathies/etiology ; Endothelial Cells/metabolism ; Endothelium, Vascular/drug effects ; Glucagon/adverse effects ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Humans ; Insulin/blood ; Male ; Middle Aged ; Nitroglycerin/pharmacology ; Peptide Fragments/adverse effects ; Pilot Projects ; Protein Precursors/adverse effects ; Receptors, Glucagon/metabolism ; Regional Blood Flow ; Vasodilation

GLP-1 stimulates insulin secretion, suppresses glucagon secretion, delays gastric emptying, and inhibits small bowel motility, all actions contributing to the anti-diabetogenic peptide effect. Endothelial dysfunction is strongly associated with insulin resistance and type 2 diabetes mellitus and may cause the angiopathy typifying this debilitating disease. Therefore, interventions affecting both endothelial dysfunction and insulin resistance may prove useful in improving survival in type 2 diabetes patients. We investigated GLP-1's effect on endothelial function and insulin sensitivity (S(I)) in two groups: 1) 12 type 2 diabetes patients with stable coronary artery disease and 2) 10 healthy subjects with normal endothelial function and S(I). Subjects underwent infusion of recombinant GLP-1 or saline in a random crossover study. Endothelial function was measured by postischemic FMD of brachial artery, using ultrasonography. S(I) [in (10(-4) dl.kg(-1).min(-1))/(muU/ml)] was measured by hyperinsulinemic isoglycemic clamp technique. In type 2 diabetic subjects, GLP-1 infusion significantly increased relative changes in brachial artery diameter from baseline FMD(%) (3.1 +/- 0.6 vs. 6.6 +/- 1.0%, P < 0.05), with no significant effects on S(I) (4.5 +/- 0.8 vs. 5.2 +/- 0.9, P = NS). In healthy subjects, GLP-1 infusion affected neither FMD(%) (11.9 +/- 0.9 vs. 10.3 +/- 1.0%, P = NS) nor S(I) (14.8 +/- 1.8 vs. 11.6 +/- 2.0, P = NS). We conclude that GLP-1 improves endothelial dysfunction but not insulin resistance in type 2 diabetic patients with coronary heart disease. This beneficial vascular effect of GLP-1 adds yet another salutary property of the peptide useful in diabetes treatment.

0 (GLP1R protein, human)
0 (Glucagon-Like Peptide-1 Receptor)
0 (Insulin)
0 (Peptide Fragments)
0 (Protein Precursors)
0 (Receptors, Glucagon)
89750-14-1 (Glucagon-Like Peptide 1)
9007-92-5 (Glucagon)
G59M7S0WS3 (Nitroglycerin)

Date Created: 20040909 Date Completed: 20041216 Latest Revision: 20220408

20240628

10.1152/ajpendo.00237.2004

15353407