Physiology and pathophysiology of IGFBP-1 and IGFBP-2 – Consensus and dissent on metabolic control and malignant potential

Publication date: Available online 8 July 2015 Source:Best Practice & Research Clinical Endocrinology & Metabolism Author(s): Andreas Hoeflich, Vincenzo C. Russo IGFBP-1 and IGFBP-2 are suppressed by growth hormone and therefore represent less prominent members of the IGFBP family when compared to IGFBP-3 that carries most of the IGFs during circulation under normal conditions in humans in vivo. As soon as the GH signal is decreased expression of IGF-I and IGFBP-3 is reduced. Under conditions of lowered suppression by GH the time seems come for IGFBP-1 and IGFBP-2. Both IGFBPs are potent effectors of growth and metabolism. Secretion of IGFBP-1 and IGFBP-2 is further suppressed by insulin and diminished with increasing obesity. Both IGFBP family members share the RGD sequence motif that mediates binding to integrins and is linked to PTEN/PI3K signalling. In mice, IGFBP-2 prevents age- and diet-dependent glucose insensitivity and blocks differentiation of preadipocytes. The latter function is modulated by two distinct heparin-binding domains of IGFBP-2 which are lacking in IGFBP-1. IGFBP-2 is further regulated by leptin and has been demonstrated to affect insulin sensitivity and glucose tolerance, further supporting a particular role of IGFBP-2 in glucose and fat metabolism. Since IGFBP-2 is controlled by sex steroids as well, we devised a scheme to compare IGFBP effects in breast, ovarian and prostate cancer. While a positive association does not seem ...
Source: Best Practice and Research Clinical Endocrinology and Metabolism - Category: Endocrinology Source Type: research