Small molecule modulation of insulin receptor-insulin like growth factor-1 receptor heterodimers in human endothelial cells
We identified a small molecule that decreases the formation of IR: IGF-1R hybrid receptors in human endothelial cells, without significant impact on the overall expression of IR or IGF-1R. In HUVECs, reduction of IR: IGF-1R hybrid receptors leads to an increase in insulin-induced serine phosphorylation of the critical downstream signalling kinase, Akt. The underpinning mechanism appears, at least in part to involve the attenuation of the inhibitory effect of IR: IGF-1R hybrid receptors on PI3-kinase signalling.
Authors
- Hema Viswambharan (ORCID: https://orcid.org/0000-0002-7616-5026)
- Mark T. Kearney (ORCID: https://orcid.org/0000-0002-9376-8814)
- David J. Beech (ORCID: https://orcid.org/0000-0002-7683-9422)
- Katie J. Simmons (ORCID: https://orcid.org/0000-0003-4846-9097)
- Katherine Bridge (ORCID: https://orcid.org/0000-0003-0495-9465)
- Martin J. McPhillie (ORCID: https://orcid.org/0000-0001-8264-8211)
- Natalie J Haywood (ORCID: https://orcid.org/0000-0002-8762-7257)
- Colin W. G. Fishwick (ORCID: https://orcid.org/0000-0003-1283-2181)
- Tarik Issad (ORCID: https://orcid.org/0000-0002-2638-6330)
- Paul J. Meakin (ORCID: https://orcid.org/0000-0002-8553-3863)
- Karen E. Porter (ORCID: https://orcid.org/0000-0002-6442-7420)
- Chloe Wilkinson (ORCID: https://orcid.org/0000-0002-7471-6429)
- Tom Armstrong (ORCID: https://orcid.org/0000-0002-2362-5332)
- Lydia Lunn
- Richard M. Cubbon (ORCID: https://orcid.org/0000-0001-7844-3600)
- Samuel Turvey (ORCID: https://orcid.org/0000-0003-4298-8339)
- Stephen G. Wheatcroft (ORCID: https://orcid.org/0000-0002-0512-3275)
- Eva Clavane (ORCID: https://orcid.org/0000-0003-0568-1944)
Institutions
- Centre National de la Recherche Scientifique (FR)
- University of Leeds (GB)
- Inserm (FR)
- Université Paris Cité (FR)
- Institut Cochin (FR)
Publication Details
- Journal
- Molecular and Cellular Endocrinology
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1016/j.mce.2024.112387
- Citations
- 1
- Primary Topic
- Growth Hormone and Insulin-like Growth Factors
- Type
- article
- Field-Weighted Citation Impact
- 0.36
Funders
- National Institute for Health and Care Research
- British Heart Foundation