William L. Lowe

Regulation by fasting of rat insulin-like growth factor I and its receptor. Effects on gene expression and binding.

We have examined, in liver and extrahepatic tissues, the effects of fasting on total insulin-like growth factor I (IGF-I) mRNA levels, on levels of different IGF-I mRNAs generated by alternative splicing of the primary IGF-I transcript, and on IGF-I receptor binding and mRNA levels. A 48-h fast decreased total IGF-I mRNA levels by approximately 80% in lung and liver, approximately 60% in kidney and muscle, and only approximately 30-40% in stomach, brain, and testes. In heart, IGF-I mRNA levels did not change. The levels of the different splicing variants, however, were essentially coordinately regulated within a given tissue. Specific 125I-IGF-I binding in lung, testes, stomach, kidney, and heart was increased by fasting by approximately 30-100%, whereas in brain 125I-IGF-I binding did not change in response to fasting. In tissues in which fasting increased IGF-I receptor number, receptor mRNA levels increased approximately 1.6- to 2.5-fold, whereas when IGF-I receptor number was unchanged in response to fasting, receptor mRNA levels did not change. These data demonstrate that the change in IGF-I and IGF-I receptor mRNA levels during fasting is quantitatively different in different tissues and suggest that regulation of IGF-I and IGF-I receptor gene expression by fasting is discoordinate.

Insulin Receptors in the Brain

This review briefly outlines the studies demonstrating specific insulin receptors in brain, describes the recent studies on the structure and function of these receptors, and concludes with suggestions for future studies for exploring the function of insulin on nervous tissue.

Transcriptional Diversity in Rat Insulin-Like Growth Factor I Gene Expression

Insulin-like growth factor I (IGF-I), or Somatomedin C, is a member of a family of insulin-like peptides which also includes insulin itself, insulin-like growth factor II (IGF-II) or multiplication-stimulating activity (MSA), and, in some schemes, relaxin (1,2,3). The IGFs are similar to proinsulin in that they contain B and A domains separated by a C peptide sequence, but differ in that the mature IGF-I proteins retain their C peptide moeities and therefore consist of single polypeptide chains. Additionally, the mature forms of the IGFs contain a carboxy-terminal D domain not found in insulin (2,4,5). Finally, as discussed in more detail below with respect to IGF-I, cDNA sequences corresponding to IGF-I and IGF-II mRNAs suggest the presence of an additional carboxy-terminal E peptide predicted to be a component of the IGF-I and IGF-II pro-hormones (6,7,8,9).