The regulation of glucose uptake and mass in skeletal muscle are essential for the maintenance of functional capacity, general health, and quality of life. Skeletal muscle can be categorised into two major types, glycolytic and oxidative muscles. The regulation of muscle glucose uptake varies between the two muscle types, dependent on specific conditions, such as whether or not insulin is present, and whether the muscle is at rest or following exercise. Furthermore, muscle atrophy in response to disuse, disease or aging also occurs in a muscle type-specific manner. However, the exact mechanisms underlying these muscle type specificities still remain unclear.
Emerging evidence indicates that undercarboxylated osteocalcin (ucOC), a hormone secreted from bone, may play a role in the regulation of muscle glucose uptake and muscle mass. The signalling pathways underlying the ucOC effect on muscle are not clear, but may include G protein-coupled receptor, class C, group 6, member A (GPRC6A) as the receptor, along with the activation of protein kinase B (Akt), extracellular signal-regulated kinases (ERK), 5' adenosine monophosphate-activated protein kinase (AMPK), protein kinase C (PKC), Akt substrate of 160kD (AS160), mammalian target of rapamycin complex 1 (mTORC1), and/or the class O of forkhead box transcription factors (FOXOs). It is also not clear whether the effect of ucOC on muscle glucose uptake and the loss of ucOC signalling during muscle atrophy are muscle type-specific, contributing to the muscle type specificities in glucose uptake regulation and muscle wasting, respectively. Therefore, this PhD thesis aimed to explore the link between ucOC and muscle glucose uptake (under various conditions) and muscle mass in glycolytic and oxidative muscles, as well as investigate the underlying mechanisms.
The thesis contains four separate but related studies, all of which have been published in top journals in the area of bone and mineral research.