Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor
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 recognit...
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Published: |
Society of Neuroscience
2002
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| Subjects: | |
| Online Access: | http://www.jneurosci.org/content/vol22/issue10/ http://hdl.handle.net/20.500.11937/19003 |
| _version_ | 1848749909221572608 |
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| author | Xie, Ling Helmerhorst, Erik Plewright, Brian Van Bronswijk, Wilhelm Martins, R. |
| author_facet | Xie, Ling Helmerhorst, Erik Plewright, Brian Van Bronswijk, Wilhelm Martins, R. |
| author_sort | Xie, Ling |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T07:28:25Z |
| format | Journal Article |
| id | curtin-20.500.11937-19003 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:28:25Z |
| publishDate | 2002 |
| publisher | Society of Neuroscience |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-190032017-08-23T07:51:42Z Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor Xie, Ling Helmerhorst, Erik Plewright, Brian Van Bronswijk, Wilhelm Martins, R. insulin binding Scatchard analysis diabetes Alzheimer's disease insulin receptors amyloid- peptide 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. 2002 Journal Article http://hdl.handle.net/20.500.11937/19003 http://www.jneurosci.org/content/vol22/issue10/ Society of Neuroscience fulltext |
| spellingShingle | insulin binding Scatchard analysis diabetes Alzheimer's disease insulin receptors amyloid- peptide Xie, Ling Helmerhorst, Erik Plewright, Brian Van Bronswijk, Wilhelm Martins, R. Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor |
| title | Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor |
| title_full | Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor |
| title_fullStr | Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor |
| title_full_unstemmed | Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor |
| title_short | Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor |
| title_sort | alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor |
| topic | insulin binding Scatchard analysis diabetes Alzheimer's disease insulin receptors amyloid- peptide |
| url | http://www.jneurosci.org/content/vol22/issue10/ http://hdl.handle.net/20.500.11937/19003 |