[Studies on the dynamics of insulin secretion and the regulatory mechanism of insulin receptor in fetal rats].

In order to clarify the onset of insulin secretion and the regulatory mechanism of its receptor induction in fetus, blood glucose, serum insulin and its hepatic receptor in situ in fetal rats (D18-D21) were measured and the changes of the levels of insulin and its receptor after the direct injection of glucose (1g/kg) to fetal rats in utero were investigated. In fetal rats (D18-D21), both serum insulin and glucose levels increased as pregnancy progresses and specific binding of insulin in fetal liver microsomal membranes increased on D21 of gestation, mainly due to the increase in binding affinity rather than binding capacity. After the direct injection of glucose to the fetus in utero, the rapid increase in serum insulin and the rapid decrease in insulin specific binding to liver microsomal membranes were observed in a part of D20 and all of D21 fetal rats, which was mainly due to the decrease of binding capacity. This suggests that the acute elevation of endogenous insulin level followed by the decrease of insulin specific binding in fetal rat liver is based on the down regulation mechanism of insulin receptor, because the amounts of insulin separated from liver microsomal membranes were less than one twentieth of the insulin concentration which are enough to decrease the binding capacity of hepatic receptor theoretically. In addition, the dissociation of 125I-insulin from liver microsomal membranes of glucose-treated rats were indistinguishable from that of control. From these results, it can be concluded that the onset of glucose-stimulated insulin secretion appears in fetal rats on D20 of gestation and the elevation of endogeneous insulin rapidly down-regulates the number of hepatic insulin receptor in fetal rats.