Development of glucagon sensitivity in neonatal rat liver.
The ontogenesis of the hepatic glucagon-sensitive adenylate cyclase system has been studied in the rat. With a partially purified liver membrane preparation, fetal adenylate cyclase was less responsive to glucagon than the enzyme from neonatal or adult livers. Similar results were obtained in gently prepared liver homogenates, suggesting that destruction of essential components of the fetal liver membrane did not account for the relative unresponsiveness of the adenylate cyclase enzyme to glucagon. Investigation of other factors that might account for diminished fetal hepatic responsiveness to glucagon indicate (a) minimal glucagon degradation by fetal membranes relative to 8-day or adult tissue; and (b) available adenylate cyclase enzyme, as suggested by a 13-fold increase over basal cyclic AMP formation with NaF in fetal liver membranes. These results indicate that neither enhanced glucagon degradation nor adenylate cyclase enzyme deficiency accounts for the relative insensitivity of the fetal hepatic adenylate cyclase system to glucagon. In early neonatal life, hepatic adenylate cyclase responsiveness to glucagon rapidly developed and was maximal 6 days after birth. These changes were closely paralleled by a fivefold increase in glucagon binding and the kinetically determined Vmax for cyclic AMP formation. These observations suggest that (a) fetal hepatic unresponsiveness to glucagon may be explained by a limited number of glucagon receptor sites; (b) during the neonatal period, the development of glucagon binding is expressed primarily as an increase in adenylate cyclase Vmax; (c) the ontogenesis of hepatic responsiveness to glucagon may be important in the resolution of neonatal hypoglycemia.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D011247:Pregnancy; D051381:Rats
D007457:Iodine Radioisotopes; D005934:Glucagon; D000262:Adenylyl Cyclases; D005459:Fluorides