Inner ear is a target for insulin signaling and insulin resistance : evidence from mice and auditory HEI-OC1 cells
(2020) In BMJ open diabetes research & care 8.- Abstract
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... (More)
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.
(Less)
- author
- Pålbrink, Ann-Ki
LU
; Kopietz, Franziska
LU
; Morén, Björn LU
; In 't Zandt, René LU
; Kalinec, Federico ; Stenkula, Karin LU ; Göransson, Olga LU
; Holm, Cecilia LU ; Magnusson, Måns LU
and Degerman, Eva LU
- organization
-
- Insulin Signal Transduction (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- Protein Phosphorylation (research group)
- Glucose Transport and Protein Trafficking (research group)
- Lund University Bioimaging Center
- MR Physics (research group)
- Molecular Endocrinology (research group)
- Section IV
- Otorhinolaryngology (Lund)
- publishing date
- 2020-03-31
- type
- Contribution to journal
- publication status
- published
- subject
- in
- BMJ open diabetes research & care
- volume
- 8
- article number
- e000820
- publisher
- BMJ Publishing Group
- external identifiers
-
- pmid:32238362
- scopus:85082896846
- ISSN
- 2052-4897
- DOI
- 10.1136/bmjdrc-2019-000820
- project
- The inner ear as a target organ for insulin action and resistance
- language
- English
- LU publication?
- yes
- additional info
- © 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.
- id
- 2691d57a-52ca-4778-9e3e-63969bd81110
- date added to LUP
- 2020-04-17 11:31:51
- date last changed
- 2024-05-15 09:20:44
@article{2691d57a-52ca-4778-9e3e-63969bd81110, abstract = {{<p>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.</p><p>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.</p><p>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.</p><p>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.</p>}}, author = {{Pålbrink, Ann-Ki and Kopietz, Franziska and Morén, Björn and In 't Zandt, René and Kalinec, Federico and Stenkula, Karin and Göransson, Olga and Holm, Cecilia and Magnusson, Måns and Degerman, Eva}}, issn = {{2052-4897}}, language = {{eng}}, month = {{03}}, publisher = {{BMJ Publishing Group}}, series = {{BMJ open diabetes research & care}}, title = {{Inner ear is a target for insulin signaling and insulin resistance : evidence from mice and auditory HEI-OC1 cells}}, url = {{http://dx.doi.org/10.1136/bmjdrc-2019-000820}}, doi = {{10.1136/bmjdrc-2019-000820}}, volume = {{8}}, year = {{2020}}, }