title: Zucker diabetic fatty rats, a model for type 2 diabetes, develop an inner ear dysfunction that can be attenuated by losartan treatment.
abstract: Hearing loss secondary to diabetes remains under debate. In our study, we used Zucker Diabetic Fatty (ZDF) rats as an animal model of type 2 diabetes to investigate whether (1) hearing ability impairment and structural alterations of the inner ear occur in diabetes and (2) an angiotensin II receptor blocker (losartan) can protect rats from diabetic damage. Homozygous mutants were treated with a placebo or losartan and heterozygous animals served as non-diabetic controls. All animals underwent immunohistochemical and electronmicroscopical analysis. Functional testing of hearing ability was performed by click-evoked auditory brainstem responses. The present study showed significant sensorineural hearing impairment in placebo-treated diabetic rats (hearing threshold, 45.0 ± 2.1 dB SPL) compared to both non-diabetic controls (34.7 ± 4 dB SPL) and losartan-treated diabetic rats (36.1 ± 7.4 dB SPL). Concurrently, the functional decline in the placebo-treated rats was associated with significant morphological abnormalities, particularly in the intermediate cells of the stria vascularis and with strial dysfunction. These degenerative changes were indicated by the down-regulation of several pumps, ionic and cellular channels, which are involved in the cycling of K(+) and the maintenance of the endocochlear potential essential for the hearing process. Thus, the inner ear can be regarded as a target organ during hyperglycemic disorders and a metabolically induced "diabetic otopathy" may be added to angiopathy, nephropathy and neuropathy as a specific complication of diabetes mellitus. Blockade of the angiotensin II receptor can prevent this "diabetic otopathy" despite hyperglycemic serum levels.
authors.affiliation: Medical Faculty Department of Otorhinolaryngology, Research Laboratory Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, 40225, Düsseldorf, Germany. amzg@gmx.de.
authors.forename: Angela-Maria
authors.initials: AM
authors.lastname: Meyer zum Gottesberge
authors.affiliation: Department of Otorhinolaryngology, Division of Phoniatrics and Pediatric Audiology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. massing@uni-duesseldorf.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Massing
authors.affiliation: Department of Otorhinolaryngology, Research Laboratory Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. anjasasse@gmx.net.
authors.forename: Anja
authors.initials: A
authors.lastname: Sasse
authors.affiliation: Department of Otorhinolaryngology, Primary Care Department, Largo del Pozzo 71/b, 41100, Modena, Italy. silviapalma@inwind.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Palma
authors.affiliation: Department of Otorhinolaryngology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. stefan.hansen@uni-duesseldorf.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hansen
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D034381:Hearing Loss / Q000188:drug therapy*; D006943:Hyperglycemia / Q000150:complications*; D007759:Labyrinth Diseases / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D013316:Stria Vascularis / Q000187:drug effects*
chemical_list: D019808:Losartan
keywords: Connexin; Diabetes; Diabetic otopathy; Hearing loss; Kir4.1 ion channel; Na+,K+-ATPase; Stria vascularis