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Inner ear is a target for insulin signaling and insulin resistance: evidence from mice and auditory HEI-OC1 cells
OBJECTIVE: The mechanisms underlying the association between diabetes and inner ear dysfunction are not known yet. The aim of the present study is to evaluate the impact of obesity/insulin resistance on inner ear fluid homeostasis in vivo, and to investigate whether the organ of Corti could be a tar...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170413/ https://www.ncbi.nlm.nih.gov/pubmed/32238362 http://dx.doi.org/10.1136/bmjdrc-2019-000820 |
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author | Pålbrink, Ann-Ki Kopietz, Franziska Morén, Björn In 't Zandt, René Kalinec, Federico Stenkula, Karin Göransson, Olga Holm, Cecilia Magnusson, Måns Degerman, Eva |
author_facet | Pålbrink, Ann-Ki Kopietz, Franziska Morén, Björn In 't Zandt, René Kalinec, Federico Stenkula, Karin Göransson, Olga Holm, Cecilia Magnusson, Måns Degerman, Eva |
author_sort | Pålbrink, Ann-Ki |
collection | PubMed |
description | OBJECTIVE: The mechanisms underlying the association between diabetes and inner ear dysfunction are not known yet. The aim of the present study is to evaluate the impact of obesity/insulin resistance on inner ear fluid homeostasis in vivo, and to investigate whether the organ of Corti could be a target tissue for insulin signaling using auditory House Ear Institute-Organ of Corti 1 (HEI-OC1) cells as an in vitro model. METHODS: High fat diet (HFD) fed C57BL/6J mice were used as a model to study the impact of insulin resistance on the inner ear. In one study, 12 C57BL/6J mice were fed either control diet or HFD and the size of the inner ear endolymphatic fluid compartment (EFC) was measured after 30 days using MRI and gadolinium contrast as a read-out. In another study, the size of the inner ear EFC was evaluated in eight C57BL/6J mice both before and after HFD feeding, with the same techniques. HEI-OC1 auditory cells were used as a model to investigate insulin signaling in organ of Corti cells. RESULTS: HFD feeding induced an expansion of the EFC in C57BL/6J mice, a hallmark of inner ear dysfunction. Insulin also induced phosphorylation of protein kinase B (PKB/Akt) at Ser473, in a PI3-kinase-dependent manner. The phosphorylation of PKB was inhibited by isoproterenol and IBMX, a general phosphodiesterase (PDE) inhibitor. PDE1B, PDE4D and the insulin-sensitive PDE3B were found expressed and catalytically active in HEI-OC1 cells. Insulin decreased and AICAR, an activator of AMP-activated protein kinase, increased the phosphorylation at the inhibitory Ser79 of acetyl-CoA carboxylase, the rate-limiting enzyme in de novo lipogenesis. Furthermore, the activity of hormone-sensitive lipase, the rate-limiting enzyme in lipolysis, was detected in HEI-OC1 cells. CONCLUSIONS: The organ of Corti could be a target tissue for insulin action, and inner ear insulin resistance might contribute to the association between diabetes and inner ear dysfunction. |
format | Online Article Text |
id | pubmed-7170413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-71704132020-04-24 Inner ear is a target for insulin signaling and insulin resistance: evidence from mice and auditory HEI-OC1 cells Pålbrink, Ann-Ki Kopietz, Franziska Morén, Björn In 't Zandt, René Kalinec, Federico Stenkula, Karin Göransson, Olga Holm, Cecilia Magnusson, Måns Degerman, Eva BMJ Open Diabetes Res Care Pathophysiology/Complications OBJECTIVE: The mechanisms underlying the association between diabetes and inner ear dysfunction are not known yet. The aim of the present study is to evaluate the impact of obesity/insulin resistance on inner ear fluid homeostasis in vivo, and to investigate whether the organ of Corti could be a target tissue for insulin signaling using auditory House Ear Institute-Organ of Corti 1 (HEI-OC1) cells as an in vitro model. METHODS: High fat diet (HFD) fed C57BL/6J mice were used as a model to study the impact of insulin resistance on the inner ear. In one study, 12 C57BL/6J mice were fed either control diet or HFD and the size of the inner ear endolymphatic fluid compartment (EFC) was measured after 30 days using MRI and gadolinium contrast as a read-out. In another study, the size of the inner ear EFC was evaluated in eight C57BL/6J mice both before and after HFD feeding, with the same techniques. HEI-OC1 auditory cells were used as a model to investigate insulin signaling in organ of Corti cells. RESULTS: HFD feeding induced an expansion of the EFC in C57BL/6J mice, a hallmark of inner ear dysfunction. Insulin also induced phosphorylation of protein kinase B (PKB/Akt) at Ser473, in a PI3-kinase-dependent manner. The phosphorylation of PKB was inhibited by isoproterenol and IBMX, a general phosphodiesterase (PDE) inhibitor. PDE1B, PDE4D and the insulin-sensitive PDE3B were found expressed and catalytically active in HEI-OC1 cells. Insulin decreased and AICAR, an activator of AMP-activated protein kinase, increased the phosphorylation at the inhibitory Ser79 of acetyl-CoA carboxylase, the rate-limiting enzyme in de novo lipogenesis. Furthermore, the activity of hormone-sensitive lipase, the rate-limiting enzyme in lipolysis, was detected in HEI-OC1 cells. CONCLUSIONS: The organ of Corti could be a target tissue for insulin action, and inner ear insulin resistance might contribute to the association between diabetes and inner ear dysfunction. BMJ Publishing Group 2020-03-31 /pmc/articles/PMC7170413/ /pubmed/32238362 http://dx.doi.org/10.1136/bmjdrc-2019-000820 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Pathophysiology/Complications Pålbrink, Ann-Ki Kopietz, Franziska Morén, Björn In 't Zandt, René Kalinec, Federico Stenkula, Karin Göransson, Olga Holm, Cecilia Magnusson, Måns Degerman, Eva Inner ear is a target for insulin signaling and insulin resistance: evidence from mice and auditory HEI-OC1 cells |
title | Inner ear is a target for insulin signaling and insulin resistance: evidence from mice and auditory HEI-OC1 cells |
title_full | Inner ear is a target for insulin signaling and insulin resistance: evidence from mice and auditory HEI-OC1 cells |
title_fullStr | Inner ear is a target for insulin signaling and insulin resistance: evidence from mice and auditory HEI-OC1 cells |
title_full_unstemmed | Inner ear is a target for insulin signaling and insulin resistance: evidence from mice and auditory HEI-OC1 cells |
title_short | Inner ear is a target for insulin signaling and insulin resistance: evidence from mice and auditory HEI-OC1 cells |
title_sort | inner ear is a target for insulin signaling and insulin resistance: evidence from mice and auditory hei-oc1 cells |
topic | Pathophysiology/Complications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170413/ https://www.ncbi.nlm.nih.gov/pubmed/32238362 http://dx.doi.org/10.1136/bmjdrc-2019-000820 |
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