Amino acid modulation of gut hormone release and defining roles of GLP-1 and insulin in muscle microcirculation and metabolism in older age

Abdulla, Haitham M.A. (2018) Amino acid modulation of gut hormone release and defining roles of GLP-1 and insulin in muscle microcirculation and metabolism in older age. PhD thesis, University of Nottingham.

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Abstract

Background: Skeletal muscle’s role as an organ extends beyond its classical function of locomotion. It represents an important metabolic repository for both glucose and amino acids. Its responses to nutrition, ageing and hormonal intervention continue to be an area of renewed debate. In addition, the ageing process is known for its multisystemic impact on human physiology. Little is known though on its effect on gastrointestinal gut hormone release in response to amino acids stimuli.

Aims: To investigate whether essential amino acids are capable of eliciting an “incretin effect” and assess whether the ageing process does impact EAA stimulated gut incretin release; to define the role of glucagon like peptide -1 on skeletal muscle microcirculatory parameters and glucose uptake under different concentrations of insulin; to define role of glucagon like peptide - 1 role on skeletal muscle protein metabolism under different insulin concentrations and to assess the role of insulin in regulation of human skeletal muscle protein metabolism.

Design: 40 volunteers divided in 5 groups were recruited to take part. 8 young men (20-40 yrs) were given 15 g of oral essential amino acids beverage and were compared to two other groups of 9 young men (20-40 yrs) who had 15g infusion of EAA and 8 older men (56-75 yrs) who had the same oral beverage. Further 2 groups of 7 and 8 older men (aged 65-75) underwent hyperglycaemic postabsorptive and postprandial insulin clamps respectively with and without glucagon like peptide – 1 (GLP-1).

Results: Essential amino acid delivered an approximate 45% incretin effect on calculating insulin response in the first 60 min following feeding. Glucose-dependent insulinotropic polypeptide levels increased following oral intake (399 pmol.L-1 vs 205 pmol.L-1, p<0.05) coinciding with insulin elevations. At post-prandial insulin concentration, GLP-1 increased acute myofibrillar protein synthesis, expressed as fractional synthesis rate in the fed state (mean 0.063 ± 0.004 with GLP-1 vs 0.102 ± 0.005 %.h.-1 without GLP-1, p < 0.001). GLP-1 infusion produced a significant increase in microvascular blood flow under postabsorptive and postprandial insulin levels (p < 0.05) with an increase in microvascular blood volume only under postabsorptive insulin levels (p < 0.05). On an assessment of the role of insulin on human skeletal muscle protein turnover, insulin significantly reduced MPB (WMD −15.46 [95% CI −19.74, −11.18], p<0.001) without effect on muscle protein synthesis (WMD 3.90 [95% CI −0.74, 8.55], p=0.71).

Conclusion: Age related decline in muscle mass and strength is related to blunting of microvascular and intracellular responses to hormonal and nutritional stimuli. Essential amino acids are able to deliver an “incretin effect” that is not affected by the process of physiological ageing. Glucagon like peptide -1 could potentially improve muscle microcirculation and anabolic response to nutrition in older age but not glucose uptake. Insulin effect on human skeletal muscle metabolism is more towards inhibition of muscle protein breakdown and facilitation of muscle protein synthesis.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Idris, Iskandar
Atherton, Philip J.
Keywords: Essential amino acids, GLP-1, Gut hormones, Skeletal muscle metabolism, Microcirculation
Subjects: W Medicine and related subjects (NLM Classification) > WE Muscoskeletal system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 53201
Depositing User: Abdulla, Haitham
Date Deposited: 03 Apr 2019 13:20
Last Modified: 03 Apr 2019 13:20
URI: http://eprints.nottingham.ac.uk/id/eprint/53201

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