Abstract

Insulin-like growth factor I (IGF-I) signaling is mediated by insulin receptor substrate proteins (IRS). In turn, protein tyrosine phosphatase 1B (PTP1B) dephosphorylates and inactivates insulin and IGF-I receptors. IRS2-deficient mice present developmental defects in the nervous system, altered hepatic insulin signalling b-cell failure and develop type 2-like diabetes. IGF1 gene mutations cause syndromic sensorineural hearing loss in men and mice. However, the involvement of IRS2 and PTP1B, two IGF-1 downstream signaling mediators, in hearing onset and loss has not been studied. We have studied here, the hearing function and cochlear morphology of IRS2 null mice and the impact of PTP1B deficiency. Auditory brainstem responses and cochlear morphology of systemic Irs2−/−Ptpn1+/+, Irs2+/+Ptpn1-/and Irs2−/−Ptpn1−/− mice were studied at different postnatal ages. The results indicated that Irs2−/−Ptpn1+/+ mice present a profound congenital sensorineural deafness before the onset of diabetes and altered cochlear morphology compared to wild type mice. Simultaneous PTP1B deficiency in Irs2−/−Ptpn1−/− mice delays the onset of deafness. We show for the first time that IRS2 is essential for hearing and that PTP1B inhibition may be useful for the treatment of deafness associated to hyperglycemia and type 2-diabetes. We warmly thank the support of our colleagues Carlos Avendano, Deborah Burks and Lupe Camarero.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.