Structural differences between insulin receptors in the brain and peripheral target tissues

• Published in: The Journal of biological chemistry 1983-07, Vol.258 (14), p.8527-8530
• Main Authors: Heidenreich, K A, Zahniser, N R, Berhanu, P, Brandenburg, D, Olefsky, J M
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Affinity Labels - metabolism; Animals; Azides - metabolism; Biological and medical sciences; Brain - metabolism; Cell physiology; Fundamental and applied biological sciences. Psychology; Hippocampus - metabolism; Hormonal regulation; Hypothalamus - metabolism; Insulin - analogs & derivatives; Insulin - metabolism; Male; Molecular and cellular biology; Molecular Weight; Olfactory Bulb - metabolism; Organ Specificity; Rats; Rats, Inbred Strains; Receptor, Insulin - isolation & purification; Synaptic Membranes - metabolism; Synaptosomes - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)32085-4

Insulin receptors in various brain regions (olfactory tubercle, hippocampus, and hypothalamus) were photoaffinity labeled using the photoreactive analogue of insulin B2(2-nitro,4-azidophenylacetyl)-des-PheB1-insulin (NAPA-DP-insulin). A protein with an apparent Mr of 400,000 was specifically labeled with 125I-NAPA-DP-insulin in all three brain regions. When radiolabeled proteins were reduced with dithiothreitol prior to electrophoresis, specific labeling occurred predominantly in a protein with an apparent Mr of 115,000 and to a much lesser extent in a protein with an apparent Mr of 83,000. The size of these receptor proteins, based on their electrophoretic mobilities, was consistently smaller than insulin receptor proteins in adipocytes. The covalent labeling of insulin receptors in brain by 125I-NAPA-DP-insulin was not blocked by anti-insulin receptor antiserum. Additionally, in contrast to effects observed in peripheral target tissues, this antisera did not inhibit the binding of 125I-insulin to brain membranes. Neuraminidase treatment resulted in an increase in the electrophoretic mobilities of insulin receptor subunits in adipocytes, but, had no effect on receptor subunits in brain. Solubilized insulin receptors from adipocytes were retained by wheat germ agglutinin columns and specifically eluted with N-acetylglucosamine. In contrast, solubilized insulin receptors from brain did not bind to these columns. The results from this study indicate that structural differences, including molecular weight, antigenicity, and carbohydrate composition exist between insulin receptors in brain and peripheral target tissues.