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Glucose is the major source of metabolic energy in the peripheral nerve. Energy derived from glucose is mostly utilized for axonal repolarization. One route by which glucose may reach the axon is by crossing the Schwann cells that initially surround the axons. Considering the ability of neurons to control many glial cell functions, we postulated that Schwann cell glucose transporters might be transiently regulated by axonal contact. Glucose transport was studied in a cultured, differentiated rat Schwann cell line stably expressing SV40 T antigen regulated by a synthetic mouse metallothionein promoter. 3[H]-2-deoxy-D-glucose uptake was measured in cultured cells in basal and in various experimental conditions. Glucose transporter gene expression was determined after RNA isolation from cultured cells through Northern and RNAse protection assay. In vitro, Schwann cells were found to express high-affinity, insulin-insensitive, facilitative glucose transporters and predominantly GLUT1 mRNA. Schwann cell 2-deoxyglucose uptake was increased by axolemmal membranes or forskolin but unchanged by elevated glucose levels. Regulation of Schwann cell glucose transporters by axolemma and their resistance to glucose-induced down-regulation suggest extrinsic rather than intrinsic regulation that might enhance Schwann cell vulnerability to glucotoxicity.

The protein P0 has long been proposed to be responsible for the compact nature of peripheral myelin through interactions of both its extracellular and cytoplasmic domains. Recent studies support such a role for P0's extracellular region while more precise mapping of its adhesive domains are ongoing. As P0 is a member of the immunoglobulin gene superfamily and perhaps bears the closest similarity to the ancestral molecule of this whole family, these studies may also have more general implications for adhesive interactions. In addition, although long believed to be purely an inert, structural molecule, P0 has been reported to promote neurite outgrowth, which suggests a more dynamic role for this interesting molecule.