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Insulin Signal Transduction

Department of Clinical Sciences Lund

Head: Eva Degerman

Group members

Eva Degerman and Annki Påhlbrink

Collaborators:

Måns Magnusson ENT clinic, Rene in´t Zandt LBIC

Introduction

My research group has over the years identified mechanisms of insulin action and studied the interplay between insulin, cAMP and other signaling events especially in adipose tissue. We now focus on a new target for insulin action, the inner ear. Recently we could demonstrate the expression of the insulin receptor, GLUT4 and other insulin signaling components and targets in the human inner ear. This is interesting since it is well established that diabetes is associated with inner ear dysfunction, hearing and balance disorders, however, basically nothing is known about mechanisms involved.

Goals

We will:

evaluate functionally insulin and cAMP-induced signaling events in cultured sensory epithelium from healthy mice and from mice with insulin resistance and type 2 diabetes
evaluate the role of phosphodiesterases and the sodium glucose co-transporter SGLT2 on inner ear fluid homeostasis in healthy and diabetic mice using MR imaging as read-out for inner ear function
evaluate the impact of diabetes on inner ear fluid homeostasis in humans

Impact

The inner ear appears to be a novel target for insulin action. Thus, targeting insulin and cAMP signaling and insulin resistance in the inner ear may add novel knowledge on mechanism of diabetes complications as well as prevention and treatment of inner ear disorders

Highlights

Degerman E, in ’t Zandt R, Pålbrink A, Magnusson M. Vasopressin induces endolymphatic hydrops in previous normal inner ears in mice, as evaluated with 9.4 T MRI. Hearing Research. 2015 Jun 3. pii: S0378-5955(15)00116-1.

Degerman E, Rauch U, Lindberg S, Caye-Thomasen P, Hultgårdh A and Magnusson M.. Expression of insulin signalling components in the sensory epithelium of the human saccule, Cell & Tissue Research, 2013, Jun;352(3):469-78

Degerman E, Rauch U, Göransson O, Lindberg S, Hultgårdh A, Magnusson M.Identification of new signaling components in the sensory epithelium of human saccule. Front Neurol. 2011 Aug 5;2:48.

Degerman E, Ahmad F, Chung YW, Guirguis E, Omar B, Stenson L, Manganiello V. From PDE3B to the regulation of energy homeostasis. Curr Opin Pharmacol. 2011 Dec;11(6):676-82.