IGF-dependent and IGF-independent actions of IGF-binding protein-1 and -2: implications for metabolic homeostasis.
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.
Wheatcroft
Stephen B
SB
Division of Cardiovascular & Diabetes Research, Leeds Institute of Genetics, Health & Therapeutics, University of Leeds, Leeds, UK.
Kearney
Mark T
MT
D000818:Animals; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism / Q000502:physiology*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D013002:Somatomedins / Q000378:metabolism*
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D013002:Somatomedins