Glucagon-like peptide 1 infusions overcome anabolic resistance to feeding in older human muscle

Abdulla, Haitham; Phillips, Bethan E.; Wilkinson, Daniel J.; Limb, Marie; Jandova, Tereza; Bass, Joseph J.; Rankin, Debbie; Cegielski, Jessica; Sayda, Mariwan; Crossland, Hannah; Williams, John P.; Smith, Kenneth; Idris, Iskandar; Atherton, Philip J.

Abstract

© 2020 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd Background: Despite its known insulin-independent effects, glucagon-like peptide-1 (GLP-1) role in muscle protein turnover has not been explored under fed-state conditions or in the context of older age, when declines in insulin sensitivity and protein anabolism, as well as losses of muscle mass and function, occur. Methods: Eight older-aged men (71±1year, mean±SEM) were studied in a crossover trial. Baseline measures were taken over 3hr, prior to a 3hr postprandial insulin (~30mIUml−1) and glucose (7–7.5mM) clamp, alongside I.V. infusions of octreotide and Vamin 14 (±infusions of GLP-1). Four muscle biopsies were taken, and muscle protein turnover was quantified via incorporation of 13C6 phenylalanine and arteriovenous balance kinetics, using mass spectrometry. Leg macro- and microvascular flow was assessed via ultrasound and anabolic signalling by immunoblotting. GLP-1 and insulin were measured by ELISA. Results: GLP-1 augmented muscle protein synthesis (MPS; fasted: 0.058±0.004%hr−1 vs. postprandial: 0.102±0.005%hr−1, p

Citation

Abdulla, H., Phillips, B. E., Wilkinson, D. J., Limb, M., Jandova, T., Bass, J. J., …Atherton, P. J. (2020). Glucagon-like peptide 1 infusions overcome anabolic resistance to feeding in older human muscle. Aging Cell, 19(9), Article e13202. https://doi.org/10.1111/acel.13202

• Journal Article Type: Article
• Acceptance Date: Jul 3, 2020
• Online Publication Date: Aug 3, 2020
• Publication Date: Aug 3, 2020
• Deposit Date: Aug 14, 2020
• Publicly Available Date: Aug 14, 2020
• Journal: Aging Cell
• Print ISSN: 1474-9718
• Electronic ISSN: 1474-9726
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 9
• Article Number: e13202
• DOI: https://doi.org/10.1111/acel.13202
• Keywords: Glucagon‐like peptide 1
• Public URL: https://nottingham-repository.worktribe.com/output/4830706
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13202