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

Am J Physiol Endocrinol Metab. 2014 Feb 15;306(4):E355-62. doi: 10.1152/ajpendo.00283.2013. Epub 2013 Dec 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Capillaries / diagnostic imaging
  • Capillaries / drug effects*
  • Capillaries / metabolism
  • Femoral Artery / diagnostic imaging
  • Femoral Artery / drug effects
  • Femoral Artery / metabolism
  • Gastrointestinal Agents / pharmacology
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glucose / metabolism*
  • Glucose Clamp Technique
  • Humans
  • Leg / blood supply
  • Leg / diagnostic imaging
  • Male
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Octreotide / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Ultrasonography

Substances

  • Gastrointestinal Agents
  • Glucagon-Like Peptide 1
  • Glucose
  • Octreotide