GLP-1 increases microvascular recruitment but not glucose uptake in human and rat skeletal muscle

Abstract

The insulinotropic gut hormone glucagon-like peptide-1 (GLP-1) has been proposed to have effects on vascular function and glucose disposal. However, whether GLP-1 is able to increase microvascular recruitment (MVR) in humans has not been investigated. GLP-1 was infused in the femoral artery in overnight-fasted, healthy young men. Microvascular recruitment was measured with real-time contrast-enhanced ultrasound and leg glucose uptake by the leg balance technique with and without inhibition of the insulinotropic response of GLP-1 by coinfusion of octreotide. As a positive control, MVR and leg glucose uptake were measured during a hyperinsulinemic-euglycemic clamp. Infusion of GLP-1 caused a rapid increase (P < 0.05) of 20 ± 12% (mean ± SE) in MVR in the vastus lateralis muscle of the infused leg after 5 min, and MVR further increased to 60 ± 8% above preinfusion levels by 60 min infusion. The effect was slightly slower but similar in magnitude in the noninfused contralateral leg, in which GLP-1 concentration was within the physiological range. Octreotide infusion did not prevent the GLP-1-induced increase in MVR. GLP-1 infusion did not increase leg glucose uptake with or without octreotide coinfusion. GLP-1 infusion in rats increased MVR by 28% (P < 0.05) but did not increase muscle glucose uptake. During the hyperinsulinemic clamp, MVR increased ∼40%, and leg glucose uptake increased 35-fold. It is concluded that GLP-1 in physiological concentrations causes a rapid insulin-independent increase in muscle MVR but does not affect muscle glucose uptake.

Keywords: capillary recruitment; incretin hormones; insulin; microcirculation.

Figures

Fig. 1.

Schematic outline of the experiments. denotes sampling of arterialized and femoral venous blood. A: timeline for the GLP-1 and saline (negative control) experiments. B, top: timeline for the GLP-1 infusion with a pre-/coinfusion of octreotide. B, bottom: timeline for the insulin (positive control) experiments. MVR, microvascular recruitment.

Fig. 2.

MVR presented as the mean plateau value of the acoustic intensity (AI) in vastus lateralis muscle at basal and after 5-, 10-, and 60-min infusion (A) of GLP-1 in the locally infused leg, (B) infusion of GLP-1 with coinfusion of octreotide in the locally infused leg and the contralateral leg, respectively, (C) infusion of saline in the locally infused leg, and (D) before and after 60-min infusion of insulin in the antecubital vein. Different from basal: *P < 0.05; †P < 0.01; ‡P < 0.001. Bar graph values are means of n = 8 (A), n = 5 (B), n = 3 (C), and n = 6 (D) experiments; error bars are SE. All stimulated values are normalized to the individual basal.

Fig. 3.

A: MVR presented as the mean plateau value of the AI in rat hindlimb muscles at basal and after 75-min infusion of saline or saline + GLP-1. B: 2-deoxyglucose uptake in mixed gastrocnemius-soleus muscle after saline or saline + GLP-1 infusion. Different from basal, †P < 0.01. Bar graph values are means of n = 5 per experiment; error bars are SE. All stimulated AI values are normalized to the individual basal (A).