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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...

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Autores principales: Pålbrink, Ann-Ki, Kopietz, Franziska, Morén, Björn, In 't Zandt, René, Kalinec, Federico, Stenkula, Karin, Göransson, Olga, Holm, Cecilia, Magnusson, Måns, Degerman, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
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.
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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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