Expression of the Hepatic Insulin Receptor Gene in the Rat during Postnatal Development

Abstract

Changes in the expression of the liver insulin receptor are known to occur in the rat during postnatal development. To assess whether such changes occur at the level of gene expression, steady-state levels of insulin receptor mRNA and transcription rates of the receptor gene have been measured in livers of rats from birth (1 day) to adulthood (60 days). Northern blot analysis of liver RNA revealed two major insulin receptor mRNA species of 9.5 and 7.5 kb. When normalized to beta actin mRNA, insulin receptor mRNA levels increased 4-fold between 1 and 15 days, remained stable between 15 and 30 days, and decreased 2-fold between 30 and 60 days. These changes were fully suppressed by in vivo treatment with actinomycin D, an inhibitor of gene transcription. In vitro nuclear transcription assays showed that the rate of transcription of the insulin receptor gene increased 2-fold between 1 and 30 days. Insulin receptor concentration in liver membrane fractions did not exactly parallel insulin receptor mRNA levels since it increased by 20-30% from 1 to 10 days and decreased 2-fold from 10 to 60 days. During the suckling-weaning transition, insulin receptor mRNA level decreased 2-fold in rats weaned onto a high carbohydrate diet but remained unchanged in rats weaned onto a high fat diet. Throughout postnatal life, an inverse relationship was observed between liver insulin receptor mRNA and plasma insulin levels. These results show that transcriptional changes in insulin receptor gene expression occur postnatally and suggest that such changes may be insulin-related.