Characterization of the Hepatic Receptor for Insulin in the Perinatal Rat*

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Abstract
The fetus is in a constant anabolic state and responsive to insulin. To examine the possible role of the insulin cell surface receptor in mediating these effects, we have studied insulin-receptor interactions in the developing rat liver. Compared to adult hepatic membranes, specific [125I]iodoinsulin binding was approximately 2 times greater in liver tissues from 21-day-old fetal and 1-day-old neonatal rats. By several criteria (pH, temperature, and time dependencies; specificity; receptor degradation properties; and insulin dissociation characteristics), insulin receptors from perinatal and adult hepatic membranes were similar. At 20 C, however, adult hepatic membranes degraded approximately 3 times as much insulin as liver tissue from 1-day-old neonatal rats. When insulin degradation by adult hepatic membranes was minimized by incubation with N-ethylmaleimide (NEM) or at 4 C, [125I]iodoinsulin binding in perinatal liver membranes remained significantly greater. Scatchard analysis revealed curvilinear plots in both perinatal and adult membranes; the binding capacities (Ro) of 1-day-old neonatal liver membranes, however, were 90% (20 C; without NEM), 51% (20 C; with NEM), and 28% (4 C) greater than those of hepatic tissues from adult rats. Perinatal hepatic insulin receptor binding was significantly greater than in adult hepatic membranes, even though plasma insulin concentrations were 2–7 times higher in the former. Thus, an apparent lack of downregulation in fetal and 1-day-old neonatal liver membranes was observed. In summary, while perinatal and adult hepatic insulin receptors were functionally similar by several criteria, greater Ro and, perhaps, greater empty site affinity (Ke) were observed in hepatic membranes from perinatal rats. The fetal hepatic insulin receptor may thus facilitate fuel storage and organ growth during normal development.