Paper type: Journal Article, Research Support, Non-U. S. Gov'T, Review,
Impact factor: 2.431, 5-year impact factor: 2.435
Url: Not available.
Keywords: Diabetes Mellitus, Type 2, Metabolism, Humans, Islet Amyloid Polypeptide, Islets Of Langerhans, Peptide Fragments, Protein Conformation, Type 2 Metabolism, Islet Amyloid Polypeptide Metabolism, Islets Of Langerhans Metabolism, Peptide Fragments Metabolism,
Affiliations: *** IBB - CNR ***
CNR Institute of Biostructures and Bioimaging, Via P. Gaifami 18, 95126 Catania, Italy., International PhD Program in Translational Biomedicine, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.,
International PhD Program in Translational Biomedicine, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
References: Not available.
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 beta-cells mass and diffuse extracellular amyloidosis. Amyloid deposition involves the islet amyloid polypeptide (IAPP), a neuropancreatic hormone cosecreted with insulin by beta-cells. IAPP is physiologically involved in glucose homeostasis, but it may turn toxic to beta-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 beta-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 beta-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 (Abeta) misfolding.
On the Environmental Factors Affecting the Structural and Cytotoxic Properties of IAPP Peptides
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