The effects of hyperglycaemia and exercise on glucose control and metabolism: insights from in vivo and in vitro experimental models

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Carter, Steven ORCID: https://orcid.org/0000-0001-9810-0138 (2020). The effects of hyperglycaemia and exercise on glucose control and metabolism: insights from in vivo and in vitro experimental models. University of Birmingham. Ph.D.

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Abstract

Hyperglycaemia and exercise oppositely regulate human glucose metabolism, but whether these two opposite regulatory stimuli directly interact to influence resultant glucose metabolism is poorly understood. Therefore, the overarching aim of this thesis was to examine how hyperglycaemia and exercise/muscle contraction interact to regulate glucose metabolism to better understand how this interaction could be manipulated to improve human metabolic health. Chapter 4 demonstrates that prior in vitro skeletal muscle contraction blunts hyperglycaemia-induced insulin resistance in skeletal muscle cells. Chapter 5 reveals that this contraction-mediated protection coincides with increased expression of miR-194-1 and miR-1a-1 in skeletal muscle cells. Chapter 6 shows that prior hyperglycaemia blunts exercise-induced improvements in glycaemic control in healthy humans in vivo. Collectively, these results demonstrate that the timing of exercise/muscle contraction in relation to exposure to hyperglycaemia alters the resultant changes in glucose metabolism, with the first stimuli blunting the impact of the second in both cases. Overall, this thesis provides novel data that demonstrates that timing exercise to precede exposure to hyperglycaemia and/or targeting skeletal muscle miR-194-1 and miR-1a-1 expression may be effective approaches to modify the hyperglycaemia – exercise interaction and optimise human glycaemic control.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):