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 and Atherton, Philip J (2020) Glucagon-like peptide 1 infusions overcome anabolic resistance to feeding in older human muscle. Aging cell. e13202. ISSN 1474-9726.

[img]
Preview
Text (PDF file format)
Aging Cell.pdf - Published Version
Available under License Creative Commons Attribution 4.0.

Download (739kB) | Preview
Official URL: https://onlinelibrary.wiley.com/doi/full/10.1111/a...

Abstract

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 ± 1 year, mean ± SEM) were studied in a crossover trial. Baseline measures were taken over 3 hr, prior to a 3 hr postprandial insulin (~30 mIU ml ) and glucose (7-7.5 mM) 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 C 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 vs. postprandial: 0.102 ± 0.005% hr , p < 0.01), in comparison with non-GLP-1 trials. Muscle protein breakdown (MPB) was reduced throughout clamp period, while net protein balance across the leg became positive in both groups. Total femoral leg blood flow was unchanged by the clamp; however, muscle microvascular blood flow (MBF) was significantly elevated in both groups, and to a significantly greater extent in the GLP-1 group (MBF: 5 ± 2 vs. 1.9 ± 1 fold change +GLP-1 and -GLP-1, respectively, p < 0.01). Activation of the Akt-mTOR signalling was similar across both trials.

CONCLUSION

GLP-1 infusion markedly enhanced postprandial microvascular perfusion and further stimulated muscle protein metabolism, primarily through increased MPS, during a postprandial insulin hyperaminoacidaemic clamp.

Item Type: Article
Subjects: WE Musculoskeletal. Orthopaedics
WK Endocrine system. Endocrinology
WT Geriatrics. Elderly care
Divisions: Ambulatory Care > Endocrinology
Related URLs:
Depositing User: Mrs Yolande Brookes
Date Deposited: 28 Aug 2020 14:45
Last Modified: 28 Aug 2020 14:45
URI: http://www.repository.uhblibrary.co.uk/id/eprint/3387

Actions (login required)

View Item View Item