Disorders of IGFs and IGF-1R signaling pathways

The insulin-like growth factor (IGF) system comprises two ligands, IGF-I and IGF-II, that regulate multiple physiological processes, including mammalian development, metabolism and growth, through the type 1 IGF receptor (IGF-1R). The growth hormone (GH)-IGF-I axis is the major regulator of longitud...

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Bibliographic Details
Published inMolecular and cellular endocrinology Vol. 518; p. 111035
Main Authors Forbes, Briony E., Blyth, Andrew J., Wit, Jan M.
Format Journal Article
LanguageEnglish
Published Elsevier B.V 01.12.2020
Subjects
genomics
growth and development
homozygosity
humans
IGF-1R
IGF-I
IGF-I deficiency
IGF-II
IGFBPs
insulin-like growth factor I receptor
ligands
metabolism
placenta
SHORT syndrome
somatotropin
IGF-I
SHORT syndrome
IGF-1R
IGFBPs
IGF-I deficiency
IGF-II
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Summary:The insulin-like growth factor (IGF) system comprises two ligands, IGF-I and IGF-II, that regulate multiple physiological processes, including mammalian development, metabolism and growth, through the type 1 IGF receptor (IGF-1R). The growth hormone (GH)-IGF-I axis is the major regulator of longitudinal growth. IGF-II is expressed in many tissues, notably the placenta, to regulate human pre- and post-natal growth and development. This review provides a brief introduction to the IGF system and summarizes findings from reports arising from recent larger genomic sequencing studies of human genetic mutations in IGF1 and IGF2 and genes of proteins regulating IGF action, namely the IGF-1R, IGF-1R signaling pathway components and the IGF binding proteins (IGFBPs). A perspective on the effect of homozygous mutations on structure and function of the IGFs and IGF-1R is also given and this is related to the effects on growth. •Human IGF-I deficiency is associated with severe pre- and postnatal growth failure, microcephaly, intellectual impairment and sensorineural deafness.•IGF-II deficiency in humans is associated with Silver-Russell syndrome.•Homozygous defects of the human IGF1R causes a severe pre- and postnatal growth failure, microcephaly, developmental delay and elevated serum IGF-I.•Recent structures of the IGF-I:IGF-1R complex can help explain how homozygous mutations of IGF-I and IGF-1R affects their function.
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ISSN:0303-7207
1872-8057
1872-8057
DOI:10.1016/j.mce.2020.111035