Glucagon regulation of carbohydrate metabolism in rainbow trout: glucose fluxes and gene expression.

Glucagon increases fish glycaemia, but how it affects glucose fluxes has never been characterized. The goal of this study was to test the hypothesis that glucagon stimulates hepatic glucose production (rate of appearance, ) and inhibits disposal (rate of disposal, ) in rainbow trout. Changes in the mRNA abundance of key proteins involved in glycolysis, gluconeogenesis and glycogen breakdown were also monitored. The results show that glucagon increases glycaemia (+38%) by causing a temporary mismatch between and before the two fluxes converge below baseline (-17%). A novel aspect of the regulation of trout gluconeogenesis is also demonstrated: the completely different effects of glucagon on the expression of three Pepck isoforms (stimulation of , inhibition of and no response of ). Glycogen phosphorylase was modulated differently among tissues, and muscle upregulated and downregulated Glucagon failed to activate the cAMP-dependent protein kinase or FoxO1 signalling cascades. We conclude that trout hyperglycaemia results from the combination of two responses: (i) an increase in glucose induced by the stimulation of gluconeogenesis through transcriptional activation of (and possibly glycogen phosphorylase), and (ii) a decrease in glucose via inhibition of glycogen synthase and glycolysis. The observed decrease in glucose fluxes after 4 h of glucagon administration may be caused by a counter-regulatory response of insulin, potentially linked to the decrease in transcript abundance. Overall, however, these integrated effects of glucagon only lead to modest changes in glucose fluxes that partly explain why trout seem to be unable to control glycaemia very tightly.