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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

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


Authors

Haitham Abdulla

BETH PHILLIPS beth.phillips@nottingham.ac.uk
Professor of Translational Physiology

Amanda Gates

Marie Limb

Tereza Jandova

JOSEPH BASS Joseph.Bass@nottingham.ac.uk
Assistant Professor (Physiology and Endocrinology)

Johnathan Lewis

JOHN WILLIAMS john.williams7@nottingham.ac.uk
Clinical Associate Professor

KENNETH SMITH KEN.SMITH@NOTTINGHAM.AC.UK
Professor of Metabolic Mass Spectrometry

ISKANDAR IDRIS Iskandar.Idris@nottingham.ac.uk
Professor of Diabetes and Metabolic Medicine

PHILIP ATHERTON philip.atherton@nottingham.ac.uk
Professor of Clinical, metabolic & Molecular Physiology



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 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.

Citation

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. https://doi.org/10.1210/clinem/dgac613

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
DOI https://doi.org/10.1210/clinem/dgac613
Keywords Glucagon like peptide 1, extrapancreatic effects, muscle glucose uptake, muscle glucose metabolism, microvascular blood flow, microvascular recruitment, microcirculation
Public URL https://nottingham-repository.worktribe.com/output/12622044
Publisher URL https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgac613/6763659

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