title: Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease.
abstract: 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.
authors.affiliation: Dept. of Internal Medicine, Stockholm South Hospital, Karolinska Institute, Stockholm SE-118 83, Sweden. thomas.nystrom@sos.sll.se
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyström
authors.forename: Mark K
authors.initials: MK
authors.lastname: Gutniak
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.forename: Ake
authors.initials: A
authors.lastname: Sjöholm
mesh_terms: D000328:Adult; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D003326:Coronary Circulation; D003327:Coronary Disease / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005934:Glucagon / Q000009:adverse effects / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D011498:Protein Precursors / Q000009:adverse effects / Q000627:therapeutic use*; D018027:Receptors, Glucagon / Q000378:metabolism; D012039:Regional Blood Flow; D014664:Vasodilation
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005996:Nitroglycerin