title: Expression of insulin signalling components in the sensory epithelium of the human saccule.
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.
authors.affiliation: Department of Experimental Medical Sciences, Section for Diabetes, Metabolism and Endocrinology, Lund University, Biomedical Center, C11, 221 84, Lund, Sweden. eva.degerman@med.lu.se
authors.forename: Eva
authors.initials: E
authors.lastname: Degerman
authors.forename: Uwe
authors.initials: U
authors.lastname: Rauch
authors.forename: Sven
authors.initials: S
authors.lastname: Lindberg
authors.forename: Per
authors.initials: P
authors.lastname: Caye-Thomasen
authors.forename: Anna
authors.initials: A
authors.lastname: Hultgårdh
authors.forename: Måns
authors.initials: M
authors.lastname: Magnusson
mesh_terms: D051399:Aquaporin 2 / Q000378:metabolism; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000166:cytology / Q000201:enzymology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D008954:Models, Biological; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism; D012444:Saccule and Utricle / Q000166:cytology / Q000378:metabolism*; D012677:Sensation; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D051399:Aquaporin 2; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D017483:Receptors, Vasopressin; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C517272:PDE1C protein, human