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

• Published in: American journal of physiology: endocrinology and metabolism Vol. 287; no. 6; pp. E1209 - E1215
• Main Authors: Nystrom, Thomas, Gutniak, Mark K, Zhang, Qimin, Zhang, Fan, Holst, Jens Juul, Ahren, Bo, Sjoholm, Ake
• Format: Journal Article
• Language: English
• Published: United States 01.12.2004
• Subjects: Adult; Basic Medicine; Brachial Artery - drug effects; Brachial Artery - physiopathology; Coronary Circulation; Coronary Disease - drug therapy; Coronary Disease - etiology; Coronary Disease - physiopathology; Coronary Vessels - metabolism; Cross-Over Studies; Diabetes Mellitus, Type 2 - complications; Diabetic Angiopathies - drug therapy; Diabetic Angiopathies - etiology; Diabetic Angiopathies - physiopathology; Endothelial Cells - metabolism; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Fysiologi; Fysiologi och anatomi; Glucagon - adverse effects; Glucagon - therapeutic use; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Insulin - blood; insulin resistance; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Middle Aged; nitric oxide; Nitroglycerin - pharmacology; Peptide Fragments - adverse effects; Peptide Fragments - therapeutic use; Physiology; Physiology and Anatomy; Pilot Projects; Protein Precursors - adverse effects; Protein Precursors - therapeutic use; Receptors, Glucagon - metabolism; Regional Blood Flow; Vasodilation
• ISSN: 0193-1849; 1522-1555; 1522-1555
• DOI: 10.1152/ajpendo.00237.2004

1 Department of Internal Medicine, Stockholm South Hospital, Karolinska Institutet, Stockholm SE-118 83, Sweden; 2 Department of Medical Physiology, Panum Institute, University of Copenhagen, DK-1171 Copenhagen, Denmark; and 3 Department of Medicine, Lund University, 221 00 Lund, Sweden Submitted 3 June 2004 ; accepted in final form 11 August 2004 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 )/(µU/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. nitric oxide; insulin resistance Address for reprint requests and other correspondence: T. Nyström, Dept. of Internal Medicine, Södersjukhuset, Stockholm SE-118 83, Sweden (E-mail: thomas.nystrom{at}sos.sll.se )