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This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/E1209    most recent 00237.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Nyström, T. Articles by Sjöholm, A. Search for Related Content PubMed PubMed Citation Articles by Nyström, T. Articles by Sjöholm, A.

TRANSLATIONAL PHYSIOLOGY

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

Thomas Nyström,¹ Mark K. Gutniak,^1, Qimin Zhang,¹ Fan Zhang,¹ Jens Juul Holst,² Bo Ahrén,³ and Åke Sjöholm¹

¹Department of Internal Medicine, Stockholm South Hospital, Karolinska Institutet, Stockholm SE-118 83, Sweden; ²Department of Medical Physiology, Panum Institute, University of Copenhagen, DK-1171 Copenhagen, Denmark; and ³Department 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

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