Effect of immobilisation on human forearm fuel metabolism

Burns, Aisling (2019) Effect of immobilisation on human forearm fuel metabolism. PhD thesis, University of Nottingham.

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Worldwide it has been estimated that physical inactivity causes between 6-10% of global deaths, with low physical activity levels directly linked to 25-27% of the incidence of type 2 diabetes, 21-25% of breast and colon cancers, and approximately 30% of ischaemic heart disease. Thus, elucidating the underlying mechanisms between physical inactivity and the associated negative implications for health is imperative to establish and implement effective countermeasures. Currently bed rest and limb immobilisation represent the most popular experimental models used to investigate the functional and metabolic perturbations associated with physical inactivity. Forearm immobilisation was employed in each of the studies presented in this thesis, a model which allows the contralateral, non-immobilised arm to act as a within volunteer control. Furthermore, upper limb immobilisation facilitates the exploration of the reduced muscle use without the confounding effects of decreasing overall levels of physical activity and has a decreased risk of deep vein thrombosis compared to lower limb immobilisation.

The studies included in this thesis aimed to investigate the time course of metabolic and physiological changes in response to forearm immobilisation. Initial pilot work was conducted to determine which post-sampling processing methods are most appropriate to produce accurate and stable measures of whole blood glucose concentration in conjunction with the arterialised venous-venous substrate difference technique. Previous studies have shown intermittent bouts of resistance exercise during forearm immobilisation are not sufficient to protect against the decline in insulin stimulated muscle glucose uptake, a marker of insulin sensitivity, measured 36-48 hrs after the last bout of exercise. Thus, the first study in this thesis aimed to elucidate the time course of changes in insulin sensitivity over 3 days of immobilisation in 10 healthy, male volunteers and the findings revealed a marked decline (38%) in insulin sensitivity within 24 hrs of immobilisation. This reduction was sustained throughout the immobilisation period, and was not accompanied by parallel decrements in brachial artery blood flow and insulin concentration. The second study included 9 healthy, young males and aimed to investigate the impact of 2 days of immobilisation on forearm lipid clearance, for which no effect was observed. This study also aimed to identify any additional impact of increasing dietary lipid supply on decrements in insulin sensitivity and demonstrated increased dietary lipid supply does not affect the magnitude of decline in insulin sensitivity during forearm immobilisation. Overall, findings from the first two studies indicate impairments driving the rapid decline in insulin sensitivity associated with forearm immobilisation reside within the muscle. To further investigate the role of reduced muscle contraction on muscle glucose uptake during forearm immobilisation, a pilot study was carried out to determine whether regular low-grade electrically-evoked muscle contraction could blunt the immobilisation induced changes in muscle glucose uptake in response to an oral glucose challenge. The findings from this pilot study suggest that frequent muscle contraction, elicited via PES, throughout the immobilisation period is unable to prevent this decline in forearm glucose uptake.

A growing body of work links the accumulation of intramyocellular lipid during muscle disuse with reduced insulin sensitivity, thus the third study aimed to investigate any relationship between decreased insulin sensitivity with increased lipid content of forearm muscle, assessed via proton magnetic resonance spectroscopy (1H-MRS), during16 days of limb immobilisation in 5 healthy male volunteers. Additionally, changes in forearm muscle cross section area and handgrip strength were also assessed. The major findings from this study support those of the earlier studies demonstrating rapid and marked decrements in muscle insulin sensitivity, which are sustained over 8 days of immobilisation. Forearm muscle cross sectional area and handgrip strength also significantly declined, however, decrements in strength were of a much greater magnitude than muscle cross sectional area. Despite extensive method development, the scanning protocol established was unable to obtain sufficient quality data to evaluate changes in forearm lipid content associated with immobilisation. Thus, due to the small volume and structure of forearm muscles, the lower limb remains the optimal model for obtaining quality spectra using 1H-MRS.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Greenhaff, P.L.
Keywords: Physical inactivity; Immobilisation; Insulin sensitivity;
Subjects: Q Science > QP Physiology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 55977
Depositing User: Burns, Aisling
Date Deposited: 08 May 2019 12:23
Last Modified: 15 Mar 2021 04:30
URI: https://eprints.nottingham.ac.uk/id/eprint/55977

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