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IGF-dependent and IGF-independent actions of IGF-binding protein-1 and -2: implications for metabolic homeostasis
Stephen B Wheatcroft1, Mark T Kearney
1Division of Cardiovascular & Diabetes Research, Leeds Institute of Genetics, Health & Therapeutics, University of Leeds, Leeds, UK.
Abstract:
Insulin-like growth factor (IGF)-binding proteins (IGFBPs) confer temporospatial regulation to IGF bioactivity. Both stimulatory and inhibitory effects of IGFBPs on IGF actions have been described, and IGF-independent effects of several IGFBPs are emerging. Accumulating evidence indicates important roles for members of the IGFBP family in metabolic homeostasis. For example, IGFBP-1 concentrations fluctuate inversely in response to changes in plasma insulin levels, implicating IGFBP-1 in glucoregulation, and fasting levels of IGFBP-1 predict insulin sensitivity at the population level. IGFBP-2 concentrations reflect long-term insulin sensitivity and are reduced in the presence of obesity. Here, we review the evolving roles of IGFBP-1 and IGFBP-2 in metabolic homeostasis, summarize their effects on IGF bioactivity and explore putative mechanisms by which they might exert IGF-independent cellular actions.
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