The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here:

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Cecilia Holm


Default user image.

Inner ear is a target for insulin signaling and insulin resistance : evidence from mice and auditory HEI-OC1 cells


  • Ann-Ki Pålbrink
  • Franziska Kopietz
  • Björn Morén
  • René In 't Zandt
  • Federico Kalinec
  • Karin Stenkula
  • Olga Göransson
  • Cecilia Holm
  • Måns Magnusson
  • Eva Degerman

Summary, in English

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.


  • Insulin Signal Transduction
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Protein Phosphorylation
  • Glucose Transport and Protein Trafficking
  • Lund University Bioimaging Center
  • MR Physics
  • Molecular Endocrinology
  • Section IV
  • Otorhinolaryngology (Lund)

Publishing year





BMJ open diabetes research & care



Document type

Journal article


BMJ Publishing Group


  • Otorhinolaryngology
  • Endocrinology and Diabetes



Research group

  • Insulin Signal Transduction
  • Protein Phosphorylation
  • Glucose Transport and Protein Trafficking
  • MR Physics
  • Molecular Endocrinology


  • ISSN: 2052-4897