Effects of GLP-1 on Forearm Vasodilator Function and Glucose Disposal During Hyperinsulinemia in the Metabolic Syndrome

  1. Carmine Cardillo, MD2
  1. 1Department of Internal Medicine, University of Tor Vergata, Rome, Italy
  2. 2Department of Internal Medicine, Catholic University Medical School, Rome, Italy
  3. 3Department of Pharmacology, Catholic University Medical School, Rome, Italy
  4. 4Department of Biochemistry, Catholic University Medical School, Rome, Italy
  5. 5Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  1. Corresponding author: Carmine Cardillo, carmine.cardillo{at}rm.unicatt.it.

Abstract

OBJECTIVE Patients with the metabolic syndrome (MetS) have impaired insulin-induced enhancement of vasodilator responses. The incretin hormone glucagon-like peptide 1 (GLP-1), beyond its effects on blood glucose, has beneficial actions on vascular function. This study, therefore, aimed to assess whether GLP-1 affects insulin-stimulated vasodilator reactivity in patients with the MetS.

RESEARCH DESIGN AND METHODS Forearm blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in MetS patients before and after the addition of GLP-1 to an intra-arterial infusion of saline (n = 5) or insulin (n = 5). The possible involvement of oxidative stress in the vascular effects of GLP-1 in this setting was investigated by infusion of vitamin C (n = 5). The receptor specificity of GLP-1 effect during hyperinsulinemia was assessed by infusing its metabolite GLP-1(9-36) (n = 5). The metabolic actions of GLP-1 were also tested by analyzing forearm glucose disposal during hyperinsulinemia (n = 5).

RESULTS In MetS patients, GLP-1 enhanced endothelium-dependent and -independent responses to ACh and SNP, respectively, during hyperinsulinemia (P < 0.001 for both), but not during saline (P > 0.05 for both). No changes in vasodilator reactivity to ACh and SNP were seen after GLP-1 was added to insulin and vitamin C (P > 0.05 for both) and after GLP-1(9-36) was given during hyperinsulinemia (P > 0.05 for both). Also, GLP-1 did not affect forearm glucose extraction and uptake during hyperinsulinemia (P > 0.05 for both).

CONCLUSIONS In patients with the MetS, GLP-1 improves insulin-mediated enhancement of endothelium-dependent and -independent vascular reactivity. This effect may be influenced by vascular oxidative stress and is possibly exerted through a receptor-mediated mechanism.

Footnotes

  • Received April 22, 2012.
  • Accepted August 17, 2012.

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  1. Diabetes Care vol. 36 no. 3 683-689
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