Energy metabolism in mammals is regulated by mechanisms that follow a clear diurnal rhythm. Assessing glucose metabolism and insulin action for any dysregulation relevant to the risk of developing type 2 diabetes at a single point in time therefore provides only a limited picture of the 24-hour physiology of glucose homeostasis. Small and colleagues investigated the relationship between circulating insulin, insulin signaling, and glucose metabolism in vivo over multiple points of the normal diurnal cycle. The results show that reduced glucose uptake in the muscle of high fat, high sugar-fed rats over the diurnal cycle was not associated with reduced Akt signaling.
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.