Hypoglycaemia caused by overproduction of IGF2 is the result of a sequence of events, rather than one single event. Initially, IGF2 released by the tumour is bound by IGF-binding proteins in the plasma and becomes unavailable for binding to the insulin receptors on cells, for which it has only a weak affinity.
Eventually, however, the IGF2 suppresses production and secretion of pituitary growth hormone, possibly by a negative feedback mechanism, and this in turn reduces hepatic production of both IGFl and IGF-BP3. This, it is postulated, leads to a further reduction in plasma IGF2 binding capacity and, consequently, the presence in the plasma of more free or nonprotein-bound IGF2 and/or IGFl than normal. This can and does exert an insulin-like hypoglycaemic action.
