IGFBP-3 - FUNCTIONAL AND STRUCTURAL IMPLICATIONS IN AGING AND WASTINGSYNDROMES

Over the last several years, the authors have studied the relationship of insulin-like growth factors (IGFs) and the insulin-like growth fac tor binding proteins (IGFBPs) in the circulation in a number of clinic al settings. Patterns have emerged that seem to be characteristic of v arious 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 inta ct. Based on native gel electrophoresis, IGFBP-1 is in its most highly phosphorylated state in those elders who have high IGFBP-1 levels. Th is pattern is slightly different in catabolic conditions such as AIDS (wasting in adults; failure to thrive in children), uncontrolled diabe tes mellitus, trauma, and severe burns. In these conditions, serum lev els of IGF-I and -II are markedly diminished, IGFBP-3 levels are also decreased, and IGFBP-1 levels are markedly increased. In addition, the re is increased proteolysis of IGFBP-3 (AIDS failure to thrive, uncont rolled diabetes mellitus) and disruption of the ternary complex with d ecreased levels of ALS (AIDS wasting and burns). IGFBP-1 is in its mos t highly phosphorylated state in all catabolic conditions studied. Thu s, the alterations in the circulating levels of IGFs and the changes i n the physical state of the IGFBPs may lead to decreased anabolic acti vity and be a part of the mechanism of increased catabolism and wastin g.