Source:http://linkedlifedata.com/resource/pubmed/id/21067307
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3-4
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pubmed:dateCreated |
2010-11-16
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pubmed:abstractText |
Type 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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1744-2818
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
118-28
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pubmed:meshHeading |
pubmed-meshheading:21067307-Animals,
pubmed-meshheading:21067307-Blotting, Western,
pubmed-meshheading:21067307-Cell Line, Tumor,
pubmed-meshheading:21067307-Curcumin,
pubmed-meshheading:21067307-Electron Spin Resonance Spectroscopy,
pubmed-meshheading:21067307-Humans,
pubmed-meshheading:21067307-Islet Amyloid Polypeptide,
pubmed-meshheading:21067307-Islets of Langerhans,
pubmed-meshheading:21067307-Microscopy, Electron,
pubmed-meshheading:21067307-Rats,
pubmed-meshheading:21067307-Rats, Transgenic
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pubmed:year |
2010
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pubmed:articleTitle |
The effect of curcumin on human islet amyloid polypeptide misfolding and toxicity.
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pubmed:affiliation |
Larry Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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