The adrenergic control of hepatic glucose and FFA metabolism in rainbow trout (Oncorhynchus mykiss): Increased sensitivity to adrenergic stimulation with fasting

The adrenergic control of glucose and FFA release was studied in hepatocytes of rainbow trout (Oncorhynchus mykiss), which were either normally fed or fasted for 3 weeks. Isolated hepatocytes were incubated with adrenaline, noradrenaline, or isoprenaline (nonselective β-agonist). Identification of the hepatic β-adrenoceptor was combined with quantification of the difference in its affinity for adrenaline and noradrenaline. To identify the β-adrenoceptor subtype, isoprenaline incubations were combined with atenolol (selective β1-antagonist) or ICI 118,551 (selective β2-antagonist). Stimulation of the β-adrenoceptor resulted in mobilisation of glucose, which was inhibited by ICI 118,551 thus pointing to a β2-subtype. The affinity of the β2-adrenoceptor for isoprenaline and adrenaline (pD2-values of 8.3 and 7.9) was clearly higher than for noradrenaline (pD2-value of 6.5). This indicates that at physiological concentrations β2-adrenoceptors in trout are mainly stimulated by adrenaline and not by noradrenaline. A significant effect of β-adrenoceptor stimulation on the FFA release was also found, although only at high concentrations (i.e., 10−6 and 10−5 M). Again the β2-adrenoceptor appeared to mediate the stimulation of hepatic FFA release. Upon fasting, both the basal glucose and FFA release were strongly decreased. The ratio between glucose and FFA release decreased from 15.4 to 4.3 upon fasting and at this ratio the energy output for both metabolites became equal. The mobilisation of FFA upon adrenergic stimulation was relatively conserved, namely −35% upon fasting, as opposed to −89% in mobilisation of glucose. This indicates that upon fasting FFA gain importance in hepatic metabolism. The hepatic sensitivity to adrenergic stimulation is enhanced upon fasting, as indicated by an increased pD2-value from 8.3 to 8.9.