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Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1
- 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.
- Subjects :
- medicine.medical_specialty
Multidisciplinary
biology
Insulin Receptor Substrate Proteins
Insulin
medicine.medical_treatment
medicine.disease
Receptor tyrosine kinase
IRS1
Insulin receptor
Insulin resistance
Endocrinology
Insulin Receptor Substrate 4
Internal medicine
biology.protein
medicine
Insulin-like growth factor 1 receptor
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 372
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi...........cc34c73a876474f2f771280d4d0c2e67
- Full Text :
- https://doi.org/10.1038/372182a0