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pubmed-article:21067307pubmed:dateCreated2010-11-16lld:pubmed
pubmed-article:21067307pubmed:abstractTextType 2 diabetes involves aberrant misfolding of human islet amyloid polypeptide (h-IAPP) and resultant pancreatic amyloid deposits. Curcumin, a biphenolic small molecule, has offered potential benefits in other protein misfolding diseases, such as Alzheimer's disease. Our aim was to investigate whether curcumin alters h-IAPP misfolding and protects from cellular toxicity at physiologically relevant concentrations. The effect of curcumin on h-IAPP misfolding in vitro was investigated by electron paramagnetic resonance spectroscopy, ThT fluorescence and electron microscopy. Our in vitro studies revealed that curcumin significantly reduces h-IAPP fibril formation and aggregates formed in the presence of curcumin display alternative morphology and structure. We then tested a potential protective effect of curcumin against h-IAPP toxicity on ?-cells. Micromolar concentrations of curcumin partially protect INS cells from exogenous IAPP toxicity. This protective effect, however, is limited to a narrow concentration range, as curcumin becomes cytotoxic at micromolar concentrations. In different models of endogenous over-expression of h-IAPP (INS cells and h-IAPP transgenic rat islets), curcumin failed to protect ?-cells from h-IAPP-induced apoptosis. While curcumin has the ability to inhibit amyloid formation, the present data suggest that, without further modification, it is unlikely to be therapeutically useful in protection of ?-cells in type 2 diabetes.lld:pubmed
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pubmed-article:21067307pubmed:volume17lld:pubmed
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pubmed-article:21067307pubmed:pagination118-28lld:pubmed
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pubmed-article:21067307pubmed:year2010lld:pubmed
pubmed-article:21067307pubmed:articleTitleThe effect of curcumin on human islet amyloid polypeptide misfolding and toxicity.lld:pubmed
pubmed-article:21067307pubmed:affiliationLarry Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.lld:pubmed
pubmed-article:21067307pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:21067307pubmed:publicationTypeIn Vitrolld:pubmed
pubmed-article:21067307pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
pubmed-article:21067307pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed