On the Environmental Factors Affecting the Structural and Cytotoxic Properties of IAPP Peptides
Pancreatic islets in type 2 diabetes mellitus (T2DM) patients are characterized by reduced β-cells mass and diffuse extracellular amyloidosis. Amyloid deposition involves the islet amyloid polypeptide (IAPP), a neuropancreatic hormone cosecreted with insulin by β-cells. IAPP is phy...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/918573 |
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| _version_ | 1832558676692434944 |
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| author | Marianna Flora Tomasello Alessandro Sinopoli Giuseppe Pappalardo |
| author_facet | Marianna Flora Tomasello Alessandro Sinopoli Giuseppe Pappalardo |
| author_sort | Marianna Flora Tomasello |
| collection | DOAJ |
| description | Pancreatic islets in type 2 diabetes mellitus (T2DM) patients are characterized by
reduced β-cells mass and diffuse extracellular amyloidosis. Amyloid deposition
involves the islet amyloid polypeptide (IAPP), a neuropancreatic hormone cosecreted
with insulin by β-cells. IAPP is physiologically involved in glucose homeostasis,
but it may turn toxic to β-cells owing to its tendency to misfold giving rise to oligomers and fibrils.
The process by which the unfolded IAPP starts to self-assemble and the overall factors promoting this
conversion are poorly understood. Other open questions are related to the nature of the IAPP toxic species
and how exactly β-cells die. Over the last decades, there has been growing
consensus about the notion that early molecular assemblies, notably small hIAPP oligomers, are the culprit of β-cells decline. Numerous environmental factors might affect the conformational, aggregation, and cytotoxic properties of IAPP. Herein we review recent progress in the field, focusing on the influences that membranes, pH, and metal ions may have on the conformational conversion and cytotoxicity of full-length IAPP as well as peptide fragments thereof. Current theories proposed for the mechanisms of toxicity will be also summarized together with an outline of the underlying molecular links between IAPP and amyloid beta (Aβ) misfolding. |
| format | Article |
| id | doaj-art-a56c580bc13d4c87b0a28c17f89c9000 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-a56c580bc13d4c87b0a28c17f89c90002025-02-03T01:31:52ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/918573918573On the Environmental Factors Affecting the Structural and Cytotoxic Properties of IAPP PeptidesMarianna Flora Tomasello0Alessandro Sinopoli1Giuseppe Pappalardo2CNR Institute of Biostructures and Bioimaging, Via P. Gaifami 18, 95126 Catania, ItalyInternational PhD Program in Translational Biomedicine, University of Catania, Viale A. Doria 6, 95125 Catania, ItalyCNR Institute of Biostructures and Bioimaging, Via P. Gaifami 18, 95126 Catania, ItalyPancreatic islets in type 2 diabetes mellitus (T2DM) patients are characterized by reduced β-cells mass and diffuse extracellular amyloidosis. Amyloid deposition involves the islet amyloid polypeptide (IAPP), a neuropancreatic hormone cosecreted with insulin by β-cells. IAPP is physiologically involved in glucose homeostasis, but it may turn toxic to β-cells owing to its tendency to misfold giving rise to oligomers and fibrils. The process by which the unfolded IAPP starts to self-assemble and the overall factors promoting this conversion are poorly understood. Other open questions are related to the nature of the IAPP toxic species and how exactly β-cells die. Over the last decades, there has been growing consensus about the notion that early molecular assemblies, notably small hIAPP oligomers, are the culprit of β-cells decline. Numerous environmental factors might affect the conformational, aggregation, and cytotoxic properties of IAPP. Herein we review recent progress in the field, focusing on the influences that membranes, pH, and metal ions may have on the conformational conversion and cytotoxicity of full-length IAPP as well as peptide fragments thereof. Current theories proposed for the mechanisms of toxicity will be also summarized together with an outline of the underlying molecular links between IAPP and amyloid beta (Aβ) misfolding.http://dx.doi.org/10.1155/2015/918573 |
| spellingShingle | Marianna Flora Tomasello Alessandro Sinopoli Giuseppe Pappalardo On the Environmental Factors Affecting the Structural and Cytotoxic Properties of IAPP Peptides Journal of Diabetes Research |
| title | On the Environmental Factors Affecting the Structural and Cytotoxic Properties of IAPP Peptides |
| title_full | On the Environmental Factors Affecting the Structural and Cytotoxic Properties of IAPP Peptides |
| title_fullStr | On the Environmental Factors Affecting the Structural and Cytotoxic Properties of IAPP Peptides |
| title_full_unstemmed | On the Environmental Factors Affecting the Structural and Cytotoxic Properties of IAPP Peptides |
| title_short | On the Environmental Factors Affecting the Structural and Cytotoxic Properties of IAPP Peptides |
| title_sort | on the environmental factors affecting the structural and cytotoxic properties of iapp peptides |
| url | http://dx.doi.org/10.1155/2015/918573 |
| work_keys_str_mv | AT mariannafloratomasello ontheenvironmentalfactorsaffectingthestructuralandcytotoxicpropertiesofiapppeptides AT alessandrosinopoli ontheenvironmentalfactorsaffectingthestructuralandcytotoxicpropertiesofiapppeptides AT giuseppepappalardo ontheenvironmentalfactorsaffectingthestructuralandcytotoxicpropertiesofiapppeptides |