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Reduced insulin action in muscle of high fat diet rats over the diurnal cycle is not associated with defective insulin signaling


OBJECTIVE: Energy metabolism and insulin action follow a diurnal rhythm. It is therefore important that investigations into dysregulation of these pathways are relevant to the physiology of this diurnal rhythm. METHODS: We examined glucose uptake, markers of insulin action, and the phosphorylation of insulin signaling intermediates in muscle of chow and high fat, high sucrose (HFHS) diet-fed rats over the normal diurnal cycle. RESULTS: HFHS animals displayed hyperinsulinemia but had reduced systemic glucose disposal and lower muscle glucose uptake during the feeding period. Analysis of gene expression, enzyme activity, protein abundance and phosphorylation revealed a clear diurnal regulation of substrate oxidation pathways with no difference in Akt signaling in muscle. Transfection of a constitutively active Akt2 into the muscle of HFHS rats did not rescue diet-induced reductions in insulin-stimulated glucose uptake. CONCLUSIONS: These studies suggest that reduced glucose uptake in muscle during the diurnal cycle induced by short-term HFHS-feeding is not the result of reduced insulin signaling.

Type Journal
ISBN 2212-8778 (Electronic) 2212-8778 (Linking)
Authors Small, L.; Brandon, A. E.; Parker, B. L.; Deshpande, V.; Samsudeen, A. F.; Kowalski, G. M.; Reznick, J.; Wilks, D. L.; Preston, E.; Bruce, C. R.; James, D. E.; Turner, N.; Cooney, G. J.
Responsible Garvan Author (missing name)
Publisher Name Molecular Metabolism
Published Date 2019-07-31
Published Volume 25
Published Pages 107-118
Status Published in-print
DOI 10.1016/j.molmet.2019.04.006
URL link to publisher's version