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

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., Bass, J., Lewis, J., Williams, J., Smith, K., Idris, I., & 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: 0021-972X
• Publisher: Oxford University Press
• 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