Molecular Structure, Membrane Interactions, and Toxicity of the Islet Amyloid Polypeptide in Type 2 Diabetes Mellitus
Human islet amyloid polypeptide (hIAPP) is the major component of the amyloid deposits found in the pancreatic islets of patients with type 2 diabetes mellitus (T2DM). Mature hIAPP, a 37-aa peptide, is natively unfolded in its monomeric state but forms islet amyloid in T2DM. In common with other mis...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/5639875 |
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| author | Lucie Caillon Anais R. F. Hoffmann Alexandra Botz Lucie Khemtemourian |
| author_facet | Lucie Caillon Anais R. F. Hoffmann Alexandra Botz Lucie Khemtemourian |
| author_sort | Lucie Caillon |
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| description | Human islet amyloid polypeptide (hIAPP) is the major component of the amyloid deposits found in the pancreatic islets of patients with type 2 diabetes mellitus (T2DM). Mature hIAPP, a 37-aa peptide, is natively unfolded in its monomeric state but forms islet amyloid in T2DM. In common with other misfolded and aggregated proteins, amyloid formation involves aggregation of monomers of hIAPP into oligomers, fibrils, and ultimately mature amyloid deposits. hIAPP is coproduced and stored with insulin by the pancreatic islet β-cells and is released in response to the stimuli that lead to insulin secretion. Accumulating evidence suggests that hIAPP amyloid deposits that accompany T2DM are not just an insignificant phenomenon derived from the disease progression but that hIAPP aggregation induces processes that impair the functionality and the viability of β-cells. In this review, we particularly focus on hIAPP structure, hIAPP aggregation, and hIAPP-membrane interactions. We will also discuss recent findings on the mechanism of hIAPP-membrane damage and on hIAPP-induced cell death. Finally, the development of successful antiamyloidogenic agents that prevent hIAPP fibril formation will be examined. |
| format | Article |
| id | doaj-art-9939481e49624538977a92288fe46aa6 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
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| series | Journal of Diabetes Research |
| spelling | doaj-art-9939481e49624538977a92288fe46aa62025-02-03T05:55:16ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/56398755639875Molecular Structure, Membrane Interactions, and Toxicity of the Islet Amyloid Polypeptide in Type 2 Diabetes MellitusLucie Caillon0Anais R. F. Hoffmann1Alexandra Botz2Lucie Khemtemourian3Sorbonne Universités, UPMC Univ Paris 06, Laboratoire des Biomolécules, 4 Place Jussieu, 75005 Paris, FranceSorbonne Universités, UPMC Univ Paris 06, Laboratoire des Biomolécules, 4 Place Jussieu, 75005 Paris, FranceSorbonne Universités, UPMC Univ Paris 06, Laboratoire des Biomolécules, 4 Place Jussieu, 75005 Paris, FranceSorbonne Universités, UPMC Univ Paris 06, Laboratoire des Biomolécules, 4 Place Jussieu, 75005 Paris, FranceHuman islet amyloid polypeptide (hIAPP) is the major component of the amyloid deposits found in the pancreatic islets of patients with type 2 diabetes mellitus (T2DM). Mature hIAPP, a 37-aa peptide, is natively unfolded in its monomeric state but forms islet amyloid in T2DM. In common with other misfolded and aggregated proteins, amyloid formation involves aggregation of monomers of hIAPP into oligomers, fibrils, and ultimately mature amyloid deposits. hIAPP is coproduced and stored with insulin by the pancreatic islet β-cells and is released in response to the stimuli that lead to insulin secretion. Accumulating evidence suggests that hIAPP amyloid deposits that accompany T2DM are not just an insignificant phenomenon derived from the disease progression but that hIAPP aggregation induces processes that impair the functionality and the viability of β-cells. In this review, we particularly focus on hIAPP structure, hIAPP aggregation, and hIAPP-membrane interactions. We will also discuss recent findings on the mechanism of hIAPP-membrane damage and on hIAPP-induced cell death. Finally, the development of successful antiamyloidogenic agents that prevent hIAPP fibril formation will be examined.http://dx.doi.org/10.1155/2016/5639875 |
| spellingShingle | Lucie Caillon Anais R. F. Hoffmann Alexandra Botz Lucie Khemtemourian Molecular Structure, Membrane Interactions, and Toxicity of the Islet Amyloid Polypeptide in Type 2 Diabetes Mellitus Journal of Diabetes Research |
| title | Molecular Structure, Membrane Interactions, and Toxicity of the Islet Amyloid Polypeptide in Type 2 Diabetes Mellitus |
| title_full | Molecular Structure, Membrane Interactions, and Toxicity of the Islet Amyloid Polypeptide in Type 2 Diabetes Mellitus |
| title_fullStr | Molecular Structure, Membrane Interactions, and Toxicity of the Islet Amyloid Polypeptide in Type 2 Diabetes Mellitus |
| title_full_unstemmed | Molecular Structure, Membrane Interactions, and Toxicity of the Islet Amyloid Polypeptide in Type 2 Diabetes Mellitus |
| title_short | Molecular Structure, Membrane Interactions, and Toxicity of the Islet Amyloid Polypeptide in Type 2 Diabetes Mellitus |
| title_sort | molecular structure membrane interactions and toxicity of the islet amyloid polypeptide in type 2 diabetes mellitus |
| url | http://dx.doi.org/10.1155/2016/5639875 |
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