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

Hiroyuki Tamemoto; Takashi Kadowaki; Kazuyuki Tobe; Takeshi Yagi; Hiroshi Sakura; Takaki Hayakawa; Yasuo Terauchi; Kohjiro Ueki; Yasushi Kaburagi; Shinobu Satoh; Hisahiko Sekihara; Shinji Yoshioka; Hiroyoshi Horikoshi; Yasuhide Furuta; Yoji Ikawa; Masato Kasuga; Yoshio Yazaki; Shinichi Aizawa

doi:10.1038/372182a0

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

Hiroyuki Tamemoto, Takashi Kadowaki^*, Kazuyuki Tobe, Takeshi Yagi, Hiroshi Sakura, Takaki Hayakawa, Yasuo Terauchi, Kohjiro Ueki, Yasushi Kaburagi, Shinobu Satoh, Hisahiko Sekihara, Shinji Yoshioka, Hiroyoshi Horikoshi, Yasuhide Furuta, Yoji Ikawa, Masato Kasuga, Yoshio Yazaki, Shinichi Aizawa

^*Corresponding author for this work

Faculty of Medicine

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939 Scopus citations

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 (M_r, 160-190K) on SDS polyacrylamide gel^1-3. Tyrosine-phosphorylated IRS-1 binds the 85K subunit of phosphatidylinositol 3-kinase^4,5 which may be involved in the translocation of glucose transporters^6,7 and the abundant src homology protein (ASH)/Grb2^8,9 which may be involved in activation of p2l^ras 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.

Original language	English
Pages (from-to)	182-186
Number of pages	5
Journal	Nature
Volume	372
Issue number	6502
DOIs	https://doi.org/10.1038/372182a0
State	Published - 1994

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Tamemoto, H., Kadowaki, T., Tobe, K., Yagi, T., Sakura, H., Hayakawa, T., Terauchi, Y., Ueki, K., Kaburagi, Y., Satoh, S., Sekihara, H., Yoshioka, S., Horikoshi, H., Furuta, Y., Ikawa, Y., Kasuga, M., Yazaki, Y., & Aizawa, S. (1994). Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature, 372(6502), 182-186. https://doi.org/10.1038/372182a0

@article{4b916d62c57a488b9a0f40c194c1e38a,

title = "Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1",

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.",

author = "Hiroyuki Tamemoto and Takashi Kadowaki and Kazuyuki Tobe and Takeshi Yagi and Hiroshi Sakura and Takaki Hayakawa and Yasuo Terauchi and Kohjiro Ueki and Yasushi Kaburagi and Shinobu Satoh and Hisahiko Sekihara and Shinji Yoshioka and Hiroyoshi Horikoshi and Yasuhide Furuta and Yoji Ikawa and Masato Kasuga and Yoshio Yazaki and Shinichi Aizawa",

year = "1994",

doi = "10.1038/372182a0",

language = "英語",

volume = "372",

pages = "182--186",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "6502",

}

Tamemoto, H, Kadowaki, T, Tobe, K, Yagi, T, Sakura, H, Hayakawa, T, Terauchi, Y, Ueki, K, Kaburagi, Y, Satoh, S, Sekihara, H, Yoshioka, S, Horikoshi, H, Furuta, Y, Ikawa, Y, Kasuga, M, Yazaki, Y & Aizawa, S 1994, 'Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1', Nature, vol. 372, no. 6502, pp. 182-186. https://doi.org/10.1038/372182a0

TY - JOUR

T1 - Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1

AU - Tamemoto, Hiroyuki

AU - Kadowaki, Takashi

AU - Tobe, Kazuyuki

AU - Yagi, Takeshi

AU - Sakura, Hiroshi

AU - Hayakawa, Takaki

AU - Terauchi, Yasuo

AU - Ueki, Kohjiro

AU - Kaburagi, Yasushi

AU - Satoh, Shinobu

AU - Sekihara, Hisahiko

AU - Yoshioka, Shinji

AU - Horikoshi, Hiroyoshi

AU - Furuta, Yasuhide

AU - Ikawa, Yoji

AU - Kasuga, Masato

AU - Yazaki, Yoshio

AU - Aizawa, Shinichi

PY - 1994

Y1 - 1994

N2 - 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.

AB - 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.

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U2 - 10.1038/372182a0

DO - 10.1038/372182a0

M3 - 学術論文

C2 - 7969452

AN - SCOPUS:0028032894

SN - 0028-0836

VL - 372

SP - 182

EP - 186

JO - Nature

JF - Nature

IS - 6502

ER -

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

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