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Expression of insulin signalling components in the sensory epithelium of the human saccule

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Abstract

Several studies have demonstrated a link between diabetes and the dysfunction of the inner ear. Few studies, however, have reported the signalling mechanisms involved in metabolic control in human inner ear cells. Knowledge of the expression and role of the insulin receptor and downstream signalling components in the inner ear is sparce. Our immunohistochemistry approach has shown that the insulin receptor, insulin receptor substrate 1 (IRS1), protein kinase B (PKB) and insulin-sensitive glucose transporter (GLUT4) are expressed in the sensory epithelium of the human saccule, which also exhibits expression of a calcium-sensitive cAMP/cGMP phosphodiesterase 1C (PDE1C) and the vasopressin type 2 receptor. IRS1 and PDE1C are selectively expressed in sensory epithelial hair cells, whereas the other components are expressed in sensory epithelial supporting cells or in both cell types, as judged from co-expression or non-co-expression with glial fibrillary acidic protein, a marker for supporting cells. Furthermore, IRS1 appears to be localized in association with sensory nerves, whereas GLUT4 is expressed in the peri-nuclear area of stromal cells, as is the case for aquaporin 2. Thus, the insulin receptor, insulin signalling components and selected cAMP signalling components are expressed in the human saccule. In addition to well-known mechanisms of diabetes complications, such as neuropathy and vascular lesions, the expression of these proteins in the saccule could have a role in the observed link between diabetes and balance/hearing disorders.

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Abbreviations

IRS1:

Insulin receptor substrate 1

PKB:

Protein kinase B

GLUT4:

Glucose-sensitive transporter 4

PDE:

Phosphodiesterase

V2R:

Vasopressin type 2 receptor

GFAP:

Glial fibrillary acidic protein

Aqp:

Aquaporin

PDE1C:

Calcium-sensitive cAMP/cGMP phosphodiesterase

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Acknowledgments

The authors are grateful to Gunnel Roos and Ann-Kristin Holmén-Pålbrink for excellent technical assistance and to the staff on the Surgical Ward at the Department of Neurosurgery.

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Authors and Affiliations

  1. Department of Experimental Medical Sciences, Section for Diabetes, Metabolism and Endocrinology, Lund University, Biomedical Center, C11, 221 84, Lund, Sweden

    Eva Degerman

  2. Section for Vascular Wall Biology, Lund University, Lund, Sweden

    Uwe Rauch & Anna Hultgårdh

  3. Department of Clinical Sciences, Section for Otorhinolaryngology, Lund University & Skåne University Hospital, Lund, Sweden

    Sven Lindberg & Måns Magnusson

  4. Department of Otorhinolaryngology, Head and Neck Surgery, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    Per Caye-Thomasen

  5. Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    Per Caye-Thomasen

Authors
  1. Eva Degerman
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  2. Uwe Rauch
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  3. Sven Lindberg
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  4. Per Caye-Thomasen
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  5. Anna Hultgårdh
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  6. Måns Magnusson
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Corresponding author

Correspondence to Eva Degerman.

Additional information

This work was supported by the Swedish Research Council Project 3362 (to E.D.) and 2611 (to M.M.), the Crafoord Foundation, the Swedish Society of Medicine, the A. Påhlsson Foundation and the NovoNordisk Foundation, Denmark.

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Degerman, E., Rauch, U., Lindberg, S. et al. Expression of insulin signalling components in the sensory epithelium of the human saccule. Cell Tissue Res 352, 469–478 (2013). https://doi.org/10.1007/s00441-013-1614-x

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