Glucose transporters in rat peripheral nerve: Paranodal expression of GLUT1 and GLUT3

Peripheral nerve depends on glucose oxidation to energize the repolarization of excitable axonal membranes following impulse conduction, hence requiring high-energy demands by the axon at the node of Ranvier. To enter the axon at this site, glucose must be transported from the endoneurial space across Schwann cell plasma membranes and the axolemma. Such transport is likely to be mediated by facilitative glucose transporters. Although immunohistochemical studies of peripheral nerves have detected high levels of the transporter GLUT1 in endoneurial capillaries and perineurium, localization of glucose transporters to Schwann cells or peripheral axons in vivo has not been documented. In this study, we demonstrate that the GLUT1 transporter is expressed in the plasma membrane and cytoplasm of myelinating Schwann cells around the nodes of Ranvier and in the Schmidt-Lanterman incisures, making them potential sites of transcellular glucose transport. No GLUT1 was detected in axonal membranes, GLUT3 mRNA was expressed only at low levels, but GLUT3 polypeptide was barely detected by immunocytochemistry or immunoblotting in peripheral nerve from young adult rats. However, in 13-month-old rats, GLUT3 polypeptide was present in myelinated fibers, endoneurial capillaries, and perineurium. In myelinated fibers, GLUT3 appeared to be preferentially expressed in the paranodal regions of Schwann cells and nodal axons, but was also present in the internodal aspects of these structures. The results of the present study suggest that both Schwann cell GLUT1 and axonal and Schwann cell GLUT3 are involved in the transport of glucose into the metabolically active regions of peripheral axons.