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., Rankin, D., Cegielski, J., Sayda, M., Crossland, H., Williams, J. P., Smith, K., Idris, I., & 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