Insulin stimulates protein synthesis and phospholipid signaling systems but does not regulate glucose uptake in the inner ear.
High-affinity insulin receptors exist in the organ of Corti (Kd = 1.1 +/- 0.5 nM) and in the lateral wall (stria vascularis and ligamentum spirale; Kd = 1.1 +/- 0.4 nM) of the inner ear of the guinea pig as determined by the binding of radiolabeled porcine or bovine insulin in vitro. Carrier-mediated transport of glucose (defined as the cytochalasin B-sensitive part of total uptake) was measured in vitro with 2-deoxy-D-glucose as the substrate. Its Km was 188 microM in the lateral wall (r = 0.99 and 0.94, respectively). Neither the Km nor the rates of transport (0.20 +/- 0.10 pmol/micrograms protein/hr in the organ of Corti, and 0.56 +/- 0.34 pmol/micrograms protein/hr in the lateral was) were affected by insulin. In contrast, 0.1 mM ouabain decreased deoxyglucose uptake in the organ or Corti by 37% and in the lateral wall tissues by 45% indicating the presence of an active, Na(+)-dependent transporter in these tissues. Insulin influenced both protein and lipid metabolism in the inner ear. Proteins and lipids were labeled in situ by perfusion of the perilymphatic space of the cochlea with [3]-leucine or [32P]-orthophosphate and [3H]-glycerol, respectively. Thirty nM insulin stimulated the incorporation of [3H]-leucine into protein of the organ of Corti from 39 to 56 pmol/mg protein but was ineffective in the tissues of the lateral wall. In the organ of Corti, [32P]-orthophosphate was incorporated into the phosphoinositides and phosphatidate, and 30 nM insulin increased this incorporation by 101 to 149%.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
S
S
Kresge Hearing Research Institute, University of Michigan, Ann Arbor 48109-0506.
Schacht
J
J
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D007758:Ear, Inner / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D010042:Ouabain / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D014176:Protein Biosynthesis; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D007328:Insulin; D010743:Phospholipids; D010042:Ouabain; D003847:Deoxyglucose; D011972:Receptor, Insulin