Over the last several years, the authors have studied the relationship of
insulin-like growth factors (IGFs) and the
insulin-like growth factor binding proteins (IGFBPs) in the circulation in a number of clinical settings. Patterns have emerged that seem to be characteristic of various conditions. In aging, there are marked decreases in
IGF-I and -II, normal levels of
IGFBP-3, and marked increases in
IGFBP-1 in serum. Using
ligand blotting and an
IGFBP-3 proteolysis assay, BP-3 is intact. Based on native gel electrophoresis,
IGFBP-1 is in its most highly phosphorylated state in those elders who have high
IGFBP-1 levels. This pattern is slightly different in catabolic conditions such as
AIDS (wasting in adults;
failure to thrive in children), uncontrolled
diabetes mellitus,
trauma, and severe
burns. In these conditions, serum levels of
IGF-I and -II are markedly diminished,
IGFBP-3 levels are also decreased, and
IGFBP-1 levels are markedly increased. In addition, there is increased proteolysis of
IGFBP-3 (
AIDS failure to thrive, uncontrolled
diabetes mellitus) and disruption of the ternary complex with decreased levels of ALS (
AIDS wasting and
burns).
IGFBP-1 is in its most highly phosphorylated state in all catabolic conditions studied. Thus, the alterations in the circulating levels of IGFs and the changes in the physical state of the IGFBPs may lead to decreased anabolic activity and be a part of the mechanism of increased catabolism and wasting.