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dc.contributor.authorXie, Ling
dc.contributor.authorHelmerhorst, Erik
dc.contributor.authorPlewright, Brian
dc.contributor.authorVan Bronswijk, Wilhelm
dc.contributor.authorMartins, R.
dc.identifier.citationXie, Ling and Helmerhorst, Erik and Plewright, Brian and Van Bronswijk, Wilhelm and Martins, Ralph. 2002. Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor. The Journal of Neuroscience 22 (RC221): 1-5.

The amyloid- (A) peptide is neurotoxic and associated with the pathology of Alzheimer's disease (AD). We investigated the effect of A peptides on insulin binding to the insulin receptor because it is known that (1) A and insulin are both amyloidogenic peptides sharing a common sequence recognition motif, (2) A and insulin are substrates for the same insulin degrading enzyme, and (3) impaired glucose metabolism is a characteristic event in the pathology of AD. We discovered that A1-40 and A1-42, the main physiological forms, reduced insulin binding and receptor autophosphorylation. The reduction in binding was caused by a decrease in the affinity of insulin binding to the insulin receptor. This reduction was independent of the receptor concentration. The reverse, control peptide A40-1 did not reduce insulin binding or insulin receptor autophosphorylation. These results demonstrate that A is a direct competitive inhibitor of insulin binding and action. We speculate that the increased levels of A in Alzheimer's disease may be linked to the associated insulin resistance that has been observed previously in this disease.

dc.publisherSociety of Neuroscience
dc.subjectinsulin binding
dc.subjectScatchard analysis
dc.subjectAlzheimer's disease
dc.subjectinsulin receptors
dc.subjectamyloid- peptide
dc.titleAlzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor
dc.typeJournal Article
dcterms.source.titleThe Journal of Neuroscience

Copyright 2002 Society of Neuroscience


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curtin.accessStatusOpen access
curtin.facultyDivision of Health Sciences
curtin.facultySchool of Biomedical Sciences

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