Effects of fasting and refeeding on insulin binding to liver plasma membranes and hepatocytes from normal rats

The effect of acute and chronic starvation on insulin binding to liver cells and liver cell membranes was studied in normal rats. A short-term (1 day) fasting period did not induce significant changes in insulin binding to liver plasma membranes in spite of the hypoinsulinemia present in the rats, as compared with normo-insulinemic fed controls. Longer periods of fasting (2 and 4 days) elicited an increase in insulin binding to liver membranes that was due to an increase in the number of insulin receptors rather than to changes in affinity. All groups of membranes were similar with respect to the rates of association and dissociation of hormone, degree of negative cooperativity and extents of both hormone and receptor inactivation. The fasting-induced increase of insulin binding was not a consequence of the methodological procedure for membrane isolation since the same conclusions were obtained when intact hepatocytes were used. Refeeding of fasted animals resulted in a decrease of insulin binding together with an increase of insulinemia towards the fed control values. These results suggest that the number of insulin receptors is inversely related to the circulating levels of the hormone and support the hypothesis of insulin regulating its own receptor.