Minireview: posttranscriptional regulation of the insulin and insulin-like growth factor systems

Abstract

Insulin and IGFs share structural similarities and regulate metabolic processes including glucose homeostasis. Acute alterations in glucose levels trigger rapid changes in insulin concentration and insulin signaling. These processes are tightly regulated by posttranscriptional mechanisms that alter the stability and translation of mRNAs encoding insulin and the insulin receptor. Long-term glucose homeostasis is also modulated by IGFs and IGF receptors, whose expression is likewise subject to changes in the stability and translation of the encoding mRNAs. The control of mRNA half-life and translation is governed by RNA-binding proteins and microRNAs that interact with target transcripts at the 3' and 5' untranslated regions. In this review, we describe the RNA-binding proteins and microRNAs that target the mRNAs encoding insulin, IGFs, and their receptors. We discuss how these mRNA-binding factors help to elicit timely, versatile, and tissue-specific changes in insulin and IGF function, thereby effecting critical control of energy metabolism.

Figure 1

PTB coordinately up-regulates expression of insulin and insulin receptor. Under conditions requiring insulin signaling (top of the schematic), PTB both promotes the stabilization of mRNAs encoding insulin and insulin receptor and enhances the translation of the insulin receptor mRNA. Under conditions that do not require insulin signaling (bottom of the schematic), the mRNAs encoding insulin and insulin receptor are unstable (represented as discontinuous mRNAs) and therefore cannot be used for translation.