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Effects of GLP-1 Infusion Upon Whole-body Glucose Uptake and Skeletal Muscle Perfusion During Fed-state in Older Men

Abdulla, Haitham; Phillips, Bethan; Wilkinson, Daniel; Gates, Amanda; Limb, Marie; Jandova, Tereza; Bass, Joseph; Lewis, Johnathan; Williams, John; Smith, Kenneth; Idris, Iskandar; Atherton, Philip

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Haitham Abdulla

Professor of Translational Physiology

Amanda Gates

Marie Limb

Tereza Jandova

Assistant Professor (Physiology and Endocrinology)

Johnathan Lewis

Clinical Associate Professor

Professor of Metabolic Mass Spectrometry

Professor of Diabetes and Metabolic Medicine

Professor of Clinical, metabolic & Molecular Physiology


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.

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.

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).

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.


Abdulla, H., Phillips, B., Wilkinson, D., Gates, A., Limb, M., Jandova, T., …Atherton, P. (2023). Effects of GLP-1 Infusion Upon Whole-body Glucose Uptake and Skeletal Muscle Perfusion During Fed-state in Older Men. Journal of Clinical Endocrinology and Metabolism, 108(4), 971-978.

Journal Article Type Article
Acceptance Date Oct 17, 2022
Online Publication Date Nov 24, 2022
Publication Date Apr 1, 2023
Deposit Date Oct 21, 2022
Publicly Available Date Nov 24, 2022
Journal The Journal of Clinical Endocrinology & Metabolism
Electronic ISSN 1945-7197
Publisher The Endocrine Society
Peer Reviewed Peer Reviewed
Volume 108
Issue 4
Pages 971-978
Keywords Glucagon like peptide 1, extrapancreatic effects, muscle glucose uptake, muscle glucose metabolism, microvascular blood flow, microvascular recruitment, microcirculation
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