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 affect glucose metabolism during fed-state clamps in older people. METHODS: Eight men (71 ± 1 years) were studied in a randomized crossover trial. Basal blood samples were taken before postprandial (fed-state) insulin and glucose clamps, accompanied by amino acid infusions, for 3 hours. Reflecting this, following insertions of peripheral and femoral vessels cannulae and baseline measurements, peripheral IV infusions of octreotide, insulin (Actrapid), 20% glucose, and mixed amino acids; Vamin 14-EF with or without a femoral arterial GLP-1 infusion were started. GLP-1, insulin, and C-peptide were measured by ELISA. Muscle microvascular blood flow was assessed via contrast enhanced ultrasound. Whole-body glucose handling was assayed by assessing glucose infusion rate 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 (area under the curve 16.9 ± 1.7 vs 11.4 ± 1.8 mg/kg-1/180 minutes-1, P = 0.02 ± GLP, respectively). CONCLUSIONS: The beneficial effects of GLP-1 on whole-body glycemic 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 affects other glucose-regulatory organs, reflected by greater whole-body glucose uptake.

Department of Anaesthesia University Hospitals Derby and Burton NHS Foundation Trust Derby DE22 3NE UK

Department of Endocrinology and Diabetes University Hospitals Derby and Burton NHS Foundation Trust Derby DE22 3NE UK

Department of Physiology and Biochemistry Faculty of Physical Education and Sport Charles University Prague 6 Czech Republic

Diabetes and Endocrinology Centre University Hospitals Birmingham NHS Foundation Trust Heartlands Hospitals Birmingham B9 5SS UK

MRC Versus Arthritis Centre for Musculoskeletal Ageing Research Centre of Metabolism Ageing and Physiology School of Medicine University of Nottingham Royal Derby Hospital Derby DE22 3DT UK

NIHR Nottingham BRC University of Nottingham Nottingham NG7 2UH UK

Citace poskytuje Crossref.org