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Betahistine prevents development of endolymphatic hydrops in a mouse model of insulin resistance and diabetes

Pålbrink, Ann-Ki LU ; In 't Zandt, René LU orcid ; Magnusson, Måns LU orcid and Degerman, Eva LU orcid (2023) In Acta Oto-Laryngologica 143(2). p.127-133
Abstract

BACKGROUND: Diabetes is associated with inner ear dysfunction. Furthermore, C57BL/6J mice fed high fat diet (HFD), a model for insulin resistance and diabetes, develop endolymphatic hydrops (EH).

AIM: Evaluate if betahistine, spironolactone (aldosterone antagonist) and empagliflozin (sodium -glucose cotransporter2 inhibitor) can prevent EH induced by HFD and explore potential mechanisms.

METHODS: C57BL/6J mice fed HFD were treated with respective drug. The size of the endolymphatic fluid compartment was measured using contrast enhanced MRI. Secondarily, mice treated with cilostamide, a phosphodiesterase3 inhibitor, to induce EH and HEI-OC1 auditory cells were used to study potential cellular mechanisms of... (More)

BACKGROUND: Diabetes is associated with inner ear dysfunction. Furthermore, C57BL/6J mice fed high fat diet (HFD), a model for insulin resistance and diabetes, develop endolymphatic hydrops (EH).

AIM: Evaluate if betahistine, spironolactone (aldosterone antagonist) and empagliflozin (sodium -glucose cotransporter2 inhibitor) can prevent EH induced by HFD and explore potential mechanisms.

METHODS: C57BL/6J mice fed HFD were treated with respective drug. The size of the endolymphatic fluid compartment was measured using contrast enhanced MRI. Secondarily, mice treated with cilostamide, a phosphodiesterase3 inhibitor, to induce EH and HEI-OC1 auditory cells were used to study potential cellular mechanisms of betahistine.

RESULTS: HFD-induced EH was prevented by betahistine but not by spironolactone and empagliflozin. Betahistine induced phosphorylation of protein kinaseA substrates but did not prevent cilostamide-induced EH.

CONCLUSIONS: Betahistine prevents the development of EH in mice fed HFD, most likely not involving pathways downstream of phosphodiesterase3, an enzyme with implications for dysfunction in diabetes. The finding that spironolactone did not prevent HFD-induced EH suggests different mechanisms for EH induction/treatment since spironolactone prevents EH induced by vasopressin, as previously observed.

SIGNIFICANCE: This further demonstrates that independent mechanisms can cause hydropic inner ear diseases which suggests different therapeutic approaches and emphazises the need for personalized medicine.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
endolymphatic hydrops, inner ear, cochlear diseases, Betahistin, Meniere Disease, Diabetes, Empagliflozin, Hearing
in
Acta Oto-Laryngologica
volume
143
issue
2
pages
127 - 133
publisher
Taylor & Francis
external identifiers
  • scopus:85147656441
  • pmid:36735299
ISSN
1651-2251
DOI
10.1080/00016489.2023.2171116
language
English
LU publication?
yes
id
89da3e34-182e-407a-aebc-63c76bec42e8
date added to LUP
2023-02-06 17:11:44
date last changed
2024-05-30 16:18:53
@article{89da3e34-182e-407a-aebc-63c76bec42e8,
  abstract     = {{<p>BACKGROUND: Diabetes is associated with inner ear dysfunction. Furthermore, C57BL/6J mice fed high fat diet (HFD), a model for insulin resistance and diabetes, develop endolymphatic hydrops (EH).</p><p>AIM: Evaluate if betahistine, spironolactone (aldosterone antagonist) and empagliflozin (sodium -glucose cotransporter2 inhibitor) can prevent EH induced by HFD and explore potential mechanisms.</p><p>METHODS: C57BL/6J mice fed HFD were treated with respective drug. The size of the endolymphatic fluid compartment was measured using contrast enhanced MRI. Secondarily, mice treated with cilostamide, a phosphodiesterase3 inhibitor, to induce EH and HEI-OC1 auditory cells were used to study potential cellular mechanisms of betahistine.</p><p>RESULTS: HFD-induced EH was prevented by betahistine but not by spironolactone and empagliflozin. Betahistine induced phosphorylation of protein kinaseA substrates but did not prevent cilostamide-induced EH.</p><p>CONCLUSIONS: Betahistine prevents the development of EH in mice fed HFD, most likely not involving pathways downstream of phosphodiesterase3, an enzyme with implications for dysfunction in diabetes. The finding that spironolactone did not prevent HFD-induced EH suggests different mechanisms for EH induction/treatment since spironolactone prevents EH induced by vasopressin, as previously observed.</p><p>SIGNIFICANCE: This further demonstrates that independent mechanisms can cause hydropic inner ear diseases which suggests different therapeutic approaches and emphazises the need for personalized medicine.</p>}},
  author       = {{Pålbrink, Ann-Ki and In 't Zandt, René and Magnusson, Måns and Degerman, Eva}},
  issn         = {{1651-2251}},
  keywords     = {{endolymphatic hydrops; inner ear; cochlear diseases; Betahistin; Meniere Disease; Diabetes; Empagliflozin; Hearing}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{2}},
  pages        = {{127--133}},
  publisher    = {{Taylor & Francis}},
  series       = {{Acta Oto-Laryngologica}},
  title        = {{Betahistine prevents development of endolymphatic hydrops in a mouse model of insulin resistance and diabetes}},
  url          = {{http://dx.doi.org/10.1080/00016489.2023.2171116}},
  doi          = {{10.1080/00016489.2023.2171116}},
  volume       = {{143}},
  year         = {{2023}},
}