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Timing-dependent modulation of insulin mitogenic versus metabolic signalling.

This chapter will not deal sensu stricto with the mechanisms and biological significance of pulsatile hormone secretion, the general theme of this book. Rather, we will attempt to demonstrate that timing events at the receiving end of the hormonal signal, i.e. the kinetics and duration of receptor activation in target cells and subsequent downstream signalling, can play an equally important role as that of the timing aspects of secretion, in determining the qualitative and quantitative aspects of hormonal responses. We will focus on the mechanisms that determine signalling specificity by the receptor tyrosine kinases, especially the insulin receptor and the type I insulin-like growth factor receptors (IGF-I receptor). We will be succinct and refer the reader to our recent reviews and publications on this topic and references therein.