The effects of fasting on glucagon binding and action in isolated rat hepatocytes

Abstract

The effect of fasting on the basal and glucagon-stimulated uptake of α-aminoisobutyric acid (AIB) and the binding of glucagon was studied in isolated hepatocytes from fed and 72 hr-fasted rats. The basal rate and the absolute amount of glucagon-stimulated AIB transport was significantly increased in hepatocytes from fasted rats as compared to controls when measured at 0.1 m M AIB. In both groups of animals the minimal effective hormone concentration, half maximal stimulation, and maximal stimulation of AIB transport was achieved at a similar glucagon concentration. In contrast, hepatocytes from fasted rats bound from 37% to 50% less glucagon than those from fed rats. This decrease of glucagon binding appears to be the result of a decrease in the number of binding sites rather than a consequence of a change in binding affinity or increased glucagon degradation. In conclusion, our data are supportive of the hypothesis that there exists in fasting an increased efficiency of amino acid extraction by the liver at low ambient amino acid levels. The absolute uptake of AIB in response to glucagon is similarly increased which, in conjunction with the increased glucagon levels in fasting, results in further augmentation of amino acid extraction. This alteration in glucagon action appears to be a reflection of the enhanced basal rates of AIB uptake and is unrelated to the observed alterations in glucagon binding.