Browsing by Author "Antomagesh, Femilarani"

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    Cortisol regulates skeletal muscle glucose uptake during stress in zebrafish
    (2021-12-20) Antomagesh, Femilarani; Vijayan, Matt (Mathilakath); Hansen, David Donald; Huang, Carol; Habibi, Hamid H; Storey, Douglas Gordan
    The circulating glucocorticoid (GC) levels elevate in response to stress, and this response is conserved in vertebrates. GCs play an important role in mobilizing glucose to meet the increased energy demand associated with stress. GCs have also been shown to restrict skeletal muscle glucose uptake during stress, but the mechanisms are far from clear. In this thesis, the overriding hypothesis tested was that the glucocorticoid receptor (GR) activation by GCs restricts insulin-stimulated skeletal muscle glucose uptake using zebrafish as a model. The chronic elevation of cortisol resulted in an impairment in plasma glucose clearance when subjected to a glucose tolerance test but did not modify whole-body insulin levels. Cortisol treated fish also showed decreased skeletal muscle glucose uptake and a lower glycogen content, while the transcript abundance of genes encoding enzymes involved in muscle glycogen synthesis and glycolysis were upregulated. When we tested the insulin response in the cortisol treated zebrafish, insulin-stimulated blood glucose clearance and muscle glycogen storage was affected but not the glucose uptake. Interestingly, cortisol group showed an increased insulin-induced phosphorylation of AKT in the skeletal muscle, but the phosphorylation of S6 kinase, a downstream target of AKT, was reduced. Moreover, the transcript abundance of glut1b, the most abundant GLUT identified in the zebrafish skeletal muscle, was upregulated with insulin treatment only in the cortisol treated group. Using ubiquitous GR knockout zebrafish, the results revealed that the absence of GR improved glucose tolerance with increased skeletal muscle glucose uptake. In summary, my study shows that cortisol-GR signalling restricts skeletal muscle glucose uptake and metabolism, and this may involve disrupted insulin signalling downstream of AKT activation in zebrafish.