Effects of GLP-1 infusion upon whole-body glucose uptake and skeletal muscle perfusion during fed-state in older men.

Abstract

INTRODUCTION: Ageing skeletal muscles become both insulin resistant and atrophic. The hormone glucagon-like peptide 1 (GLP-1) facilitates postprandial glucose uptake as well as augmenting muscle perfusion - independent of insulin action. We thus hypothesized exogenous GLP-1 infusions would enhance muscle perfusion and positively impact glucose metabolism during fed-state clamps in older people. METHODS: Eight men (71 ± 1y) were studied in a randomized cross-over trial. Basal blood samples were taken prior to postprandial (fed-state) insulin and glucose clamps, accompanied by amino acid infusions, for 3 h. Reflecting this, following insertions of peripheral and femoral vessels cannulae and baseline measurements, peripheral I.V infusions of octreotide, insulin (Actrapid), 20% glucose, and mixed amino acids (AA); Vamin 14-EF) ± a femoral arterial GLP-1 infusion were started. GLP-1, insulin and C-peptide were measured by ELISA. Muscle microvascular blood flow (MBF) was assessed via contrast enhanced ultrasound (CEUS). Whole-body glucose handling was assayed by assessing glucose infusion rate (GIR) parameters. RESULTS: Skeletal muscle microvascular blood flow significantly increased in response to GLP-1 vs. feeding alone (5.0 ± 2.1 vs. 1.9 ± 0.7 fold-change from basal respectively, p = 0.008), while also increasing whole-body glucose uptake (AUC 16.9 ± 1.7 vs. 11.4 ± 1.8 mg.kg-1.180 min-1, p = 0.02 ± GLP, respectively). CONCLUSIONS: The beneficial effects of GLP-1 upon whole-body glycaemic control are evident with insulin clamped at fed-state levels. GLP-1 further enhances the effects of insulin on whole-body glucose uptake in older men, underlining its role as a therapeutic target. The effects of GLP-1 in enhancing microvascular flow likely also impacts other glucose-regulatory organs, reflected by greater whole-body glucose uptake.