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Inner ear is a targ...
Inner ear is a target for insulin signaling and insulin resistance : evidence from mice and auditory HEI-OC1 cells
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- Pålbrink, Ann-Ki (författare)
- Lund University,Lunds universitet,Signaltransduktionsforskning,Forskargrupper vid Lunds universitet,Insulin Signal Transduction,Lund University Research Groups
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- Kopietz, Franziska (författare)
- Lund University,Lunds universitet,Proteinfosforylering,Forskargrupper vid Lunds universitet,Protein Phosphorylation,Lund University Research Groups
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- Morén, Björn (författare)
- Lund University,Lunds universitet,Glukostransport och proteintrafficking,Forskargrupper vid Lunds universitet,Glucose Transport and Protein Trafficking,Lund University Research Groups
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- In 't Zandt, René (författare)
- Lund University,Lunds universitet,Lund University Bioimaging Center,Medicinska fakulteten,MR Physics,Forskargrupper vid Lunds universitet,Faculty of Medicine,Lund University Research Groups
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- Kalinec, Federico (författare)
- University of California, Los Angeles
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- Stenkula, Karin (författare)
- Lund University,Lunds universitet,Glukostransport och proteintrafficking,Forskargrupper vid Lunds universitet,Glucose Transport and Protein Trafficking,Lund University Research Groups
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- Göransson, Olga (författare)
- Lund University,Lunds universitet,Proteinfosforylering,Forskargrupper vid Lunds universitet,Protein Phosphorylation,Lund University Research Groups
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- Holm, Cecilia (författare)
- Lund University,Lunds universitet,Molekylär endokrinologi,Forskargrupper vid Lunds universitet,Molecular Endocrinology,Lund University Research Groups
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- Magnusson, Måns (författare)
- Lund University,Lunds universitet,Öron-, näs- och halssjukdomar, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Otorhinolaryngology (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Degerman, Eva (författare)
- Lund University,Lunds universitet,Signaltransduktionsforskning,Forskargrupper vid Lunds universitet,Insulin Signal Transduction,Lund University Research Groups
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(creator_code:org_t)
- 2020-03-31
- 2020
- Engelska.
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Ingår i: BMJ open diabetes research & care. - : BMJ. - 2052-4897. ; 8
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://drc.bmj.com/...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Oto-rhino-laryngologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Otorhinolaryngology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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Pålbrink, Ann-Ki
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Kopietz, Franzis ...
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Morén, Björn
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In 't Zandt, Ren ...
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Kalinec, Federic ...
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Stenkula, Karin
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visa fler...
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Göransson, Olga
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Holm, Cecilia
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Magnusson, Måns
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Degerman, Eva
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