The apparent hyperinsulinemia seen in the fetal rat in late gestation (day 20) is shown to be due to an immunoreactive insulin (IRI) species peculiar to the fetal rat, and not monomeric insulin. This species disappears within 12 h after birth and only insulin as found in the adult can then be detected. The fetal serum IRI has a molecular weight of approximately 11,000 and differs from monomeric insulin and proinsulin in its behavior on gel filtration and anion-exchange chromatography. The activity of fetal serum in an insulin bioassay based on the incorporation of glucose into lipid was half that expected on the basis of the serum IRI concentration. The addition of fetal serum to purified insulin or proinsulin caused an increase in the apparent molecular weight of both hormones by 2000. In the case of insulin, the generated species of mol wt 8000 was clearly differentiated from the endogenous species (11,000) on Sephadex G50. The fetal pancreas at this age was found to contain predominantly monomeric insulin that had full biologic activity in the insulin bioassay. It is postulated that the fetal pancreas secretes monomeric insulin, which is then modified in the circulation to a complex with reduced biologic activity. This process appears to have two steps in that in vitro fetal serum increases the apparent molecular weight of added insulin to 8000, whereas in vivo an additional component of approximately 3000 mol wt is involved to produce the endogenous insulin complex.

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