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The dynamics of insulin receptors was investigated in the feto-placenta-maternal system of DM-onset pregnant nonobese diabetic (NOD) mice. Insulin binding experiments were carried out by conventional incubation methods using cell membrane fractions (10(5) X g pellets). The results were as follows. In the case of JCL-ICR mice, used as the control, insulin specific binding in liver cell membranes, which was 26.6 +/- 3.2% in the nonpregnant state, decreased in late pregnancy (20.7 +/- 2.7%). On the other hand, in pregnant NOD mice hepatic insulin binding was 24.3 +/- 1.0%, more than that of JCL-ICR pregnant mice. By Scatchard analyses, these changes were found to be due to the changes in the number of receptors especially in high affinity sites. The serum insulin level was 6.3 +/- 4.2 microU/ml in pregnant NOD mice, which was much lower than that in other mice (nonpregnant JCL-ICR: 14.8 +/- 6.4, pregnant JCL-ICR: 37.3 +/- 18.3). In fetal liver and carcasses of NOD fetuses, insulin binding was also much greater than that in JCL-ICR fetuses. In conclusion, the hormone sensitivity to insulin was accentuated in pregnant DM-onset NOD mice not only in the maternal body but also in the fetus. This is regarded as a metabolic adaptation to the environment in the insulin deficient state of these mice. And it is speculated that insulin receptors are also down-regulated in fetal liver as well as in adult mice.
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