Insulin receptor isoforms in physiology and disease: an updated view
- Author(s)
- Belfiore, A; Malaguarnera, R; Vella, V; Lawrence, MC; Sciacca, L; Frasca, F; Morrione, A; Vigneri, R;
- Details
- Publication Year 2017-06-19,Volume 38,Issue #5,Page 379-431
- Journal Title
- Endocrine Reviews
- Publication Type
- Journal Article
- Abstract
- The insulin receptor (IR) gene undergoes differential splicing that generates two IR isoforms, IR-A and IR-B. The physiological roles of IR isoforms are incompletely understood and appear to be determined by their different binding affinities for insulin-like growth factors, particularly for IGF-2. Predominant roles of IR-A in prenatal growth and development and of IR-B in metabolic regulation are well established. However, emerging evidence indicates that the differential expression of IR isoforms may also help explain the diversification of insulin and IGF signaling and actions in various organs and tissues, by involving not only different ligand binding affinities but also different membrane partitioning and trafficking and possibly different abilities to interact with a variety of molecular partners. Noteworthy, dysregulation of the IR-A:IR-B ratio is associated with insulin resistance, aging and increased proliferative activity of normal and neoplastic tissues, and appears to sustain detrimental effects.This review discusses novel information that has generated remarkable progress in our understanding of the physiology of IR isoforms and their role in disease. We will also focus on novel IR ligands and modulators that should now be considered as an important strategy for better and safer treatment of diabetes and cancer and possibly other IR-related diseases.
- Publisher
- Oxford Academic
- Research Division(s)
- Structural Biology
- PubMed ID
- 28973479
- Publisher's Version
- https://doi.org/10.1210/er.2017-00073
- NHMRC Grants
- NHMRC/1099595,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-10-16 01:59:48
Last Modified: 2017-10-16 02:15:30