Effects of GLP-1 on forearm vasodilator function and glucose disposal during hyperinsulinemia in the metabolic syndrome

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.

Trial registration: ClinicalTrials.gov NCT00856700.

Figures

Figure 1

Plots showing FBF responses to intra-arterial infusion of escalating doses of ACh (left) and SNP (right), during the concomitant infusion of insulin alone (○) or insulin and GLP-1 (●) in the MetS patients (top) and metabolically healthy obese control subjects (bottom). The P values refer to the comparisons of vascular responses under different conditions by two-way ANOVA for repeated measures. All values are means ± SEM.

Figure 2

Plots showing FBF responses to intra-arterial infusion of escalating doses of ACh (left) and SNP (right) during the concomitant infusion of saline (○) or GLP-1 (●) in the MetS patients. The P values refer to the comparisons of vascular responses under different conditions by two-way ANOVA for repeated measures. All values are means ± SEM.

Figure 3

Plots showing FBF responses to intra-arterial infusion of escalating doses of ACh (left) and SNP (right) during the concomitant infusion of insulin and vitamin C (○) or insulin and vitamin C and GLP-1 (●) in the MetS patients. The P values refer to the comparisons of vascular responses to ACh and SNP under different conditions by two-way ANOVA for repeated measures. All values are means ± SEM.

Figure 4

Plots showing FBF responses to intra-arterial infusion of escalating doses of ACh (left) and SNP (right) during the concomitant infusion of insulin alone (○) or insulin and GLP-1(9-36) (●) in the MetS patients. The P values refer to the comparisons of vascular responses under different conditions by two-way ANOVA for repeated measures. All values are means ± SEM.