The heterogeneity of the developing brain insulin receptor

Comparison of the adult brain insulin receptor (IR) to other tissue IR demonstrates that the former migrates approximately 10 kD faster on sodium dodecyl sulfate-polyacrylamide gel electrophoresis due to deficient sialic acid content of the asparagine N-linked carbohydrate moieties. We studied these receptors in the fetal rat (18-day) brain (approximately 125 kD) and liver (approximately 135 kD), and demonstrated that similar differences are present during fetal life. These differences are not modified by hyperglycemia associated with both mild hyperinsulinemia and normoinsulinemia/hypoinsulinemia. We further studied the specific brain cell types: neurons, glial cells, and purified microvessel preparation, and demonstrated a heterogeneity in the N-linked glycosylation of the IR within an organ (brain). The neuronal (approximately 125 kD) and microvascular (approximately 125 kD, approximately 135 kD) IR are deficient in sialic acid, thus conferring neuraminidase-insensitivity to the whole brain, whereas the glial cell IR, similar to the liver IR, exhibits neuraminidase sensitivity and migrates intermediate (approximately 128 kD) to the liver and brain IR. The functional significance of this receptor heterogeneity between various tissues and cells within the same organ (brain) remains to be determined.