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Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1

Authors :
Yoshio Yazaki
Shinji Yoshioka
Hiroyoshi Horikoshi
Takashi Kadowaki
Kazuyuki Tobe
Yoji Ikawa
Shinobu Satoh
Yasushi Kaburagi
Takeshi Yagi
Masato Kasuga
Kohjiro Ueki
Hisahiko Sekihara
Shinichi Aizawa
Yasuo Terauchi
Takaki Hayakawa
Yasuhide Furuta
Hiroshi Sakura
Hiroyuki Tamemoto
Source :
Nature. 372:182-186
Publication Year :
1994
Publisher :
Springer Science and Business Media LLC, 1994.

Abstract

INSULIN receptor substrate-1 (IRS-1) is the major substrate of insulin receptor and IGF-1 receptor tyrosine kinases; it has an apparent relative molecular mass of 160–190,000 (Mr, 160–190K) on SDS polyacrylamide gel1–3. Tyrosine-phosphorylated IRS-1 binds the 85K subunit of phosphatidylinositol 3-kinase4,5 which may be involved in the translocation of glucose transporters6,7 and the abundant src homology protein (ASH)/Grb28,9 which may be involved in activation of p2lras and MAP kinase cascade10. IRS-1 also has binding sites for Syp11 and Nck12 and other src homology 2 (SH2) signalling molecules10. To clarify the physiological roles of IRS-1 in vivo, we made mice with a targeted disruption of the IRS-1 gene locus. Mice homozygous for targeted disruption of the IRS-1 gene were born alive but were retarded in embryonal and postnatal growth. They also had resistance to the glucose-lowering effects of insulin, IGF-1 and IGF-2. These data suggest the exis-tence of both IRS-1-dependent and IRS-1-independent pathways for signal transduction of insulin and IGFs.

Details

ISSN :
14764687 and 00280836
Volume :
372
Database :
OpenAIRE
Journal :
Nature
Accession number :
edsair.doi...........cc34c73a876474f2f771280d4d0c2e67
Full Text :
https://doi.org/10.1038/372182a0