CONTROLLING INSULIN-LIKE-GROWTH-FACTOR ACTIVITY AND THE MODULATION OFINSULIN-LIKE-GROWTH-FACTOR BINDING-PROTEIN AND RECEPTOR-BINDING

The insulin-like growth factors (IGF) and insulin perform seemingly un ique roles by causing the same metabolic effect: cellular hypertrophy. Although overlapping, there are different consequences to cellular hy pertrophy induced by IGF and that induced by insulin. The IGF enhance the cell hypertrophy that is requisite for cell survival, hyperplasia, and differentiation, and insulin enhances cell hypertrophy primarily as a means to increase nutrient stores. The effects of IGF and insulin are controlled by the segregation of their receptors between differen t cell types. A model is discussed that describes the need for three h ormones (IGF-I, IGF-II, and insulin) to control nutrient partitioning. Insulin receptor localization, as well as an episodic mode of secreti on, evolved to perform the short-term action of clearing excess nutrie nts from the circulation. In contrast, a complex and interactive set o f factors ensure that maximal IGF activity occurs only when conditions are optimal for growth. A relatively invariant rate of secretion and the IGF binding proteins serve to maintain a large mutable pool of IGF . This pool exists to ensure a constant supply of IGF to maintain the basal metabolic rate and to ensure that, once a cell begins to prolife rate or differentiate, adequate exposure is available to complete the process even after severe short-term physiological insults. The IGF co ncentrations only change in response to prolonged differences in prote in and energy availabilities, environmental and body temperatures, and external stress. Also, evidence is now emerging that describes a disc rete role for trace nutrients in the regulation of IGF activity. In th is latter regard, zinc has the notable role of targeting IGF binding p roteins to the cell surface. New data are presented showing that zinc also changes the affinity of the type 1 IGF receptor and cell-associat ed IGF binding proteins to optimize IGF activity.