Insulin Receptor and Glucose Transporters in the Mammalian Cochlea

Abstract

Insulin receptors are expressed on nerve cells in the mammalian brain, but little is known about insulin signaling and the expression of the insulin receptor (IR) and glucose transporters in the cochlea. We performed immunohistochemistry and gene/protein expression analysis to characterize the expression pattern of the IR and glucose transporters in the mouse organ of Corti (OC). We also performed glucose uptake assays to explore the action of insulin and the effects of pioglitazone, an insulin sensitizer, on glucose transport in the OC. Western blots of protein extracts from OCs showed high expression of IR and glucose transporter 3 (GLUT3). Immunohistochemistry demonstrated that the IR is specifically expressed in the supporting cells of the OC. GLUT3 was found in outer and inner hair cells, in the basilar membrane (BM), the stria vascularis (SV), Reissner’s membrane and spiral ganglion neurons (SGN). Glucose transporter 1 (GLUT1) was detected at low levels in the BM, SV and Reissner’s membrane, and showed high expression in the SGN. Fluorescence glucose uptake assays revealed that hair cells take up glucose and that addition of insulin (10 nM or 1 µM) approximately doubled the rate of uptake. Pioglitazone conferred a small but nonsignificant potentiation of glucose uptake at the highest concentration of insulin. Gene expression analysis confirmed expression of IR, GLUT1 and GLUT3 mRNA in the OC. Pioglitazone significantly upregulated IR and GLUT1 mRNA expression, which was further increased by insulin. Together, these data show that insulin-stimulated glucose uptake occurs in the OC and may be associated with upregulation of both the IR and GLUT1.