Aspirin, diabetes, and amyloid: Re-examination of the inhibition of amyloid formation by aspirin and ketoprofen

Ling Hsien Tu, Harris Noor, Ping Cao, Daniel P. Raleigh

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The loss of β-cell function and β-cell death are key features of diabetes. A range of mechanisms are thought to contribute to β-cell loss, including islet amyloid formation by the neuropancreatic hormone amylin (islet amyloid polypeptide, IAPP). Islet amyloid deposition also contributes to the failure of islet transplants. There are no therapeutic strategies for the treatment or prevention of islet amyloidosis. Aspirin and the nonsteroid anti-inflammatory drug (NSAID) ketoprofen, at clinically relevant doses, have been proposed to inhibit amyloid formation by amylin and thus may hold promise for treatment of islet amyloidosis. These compounds are potentially attractive given the importance of inflammation in islet amyloidosis and given the fact that there are no anti-islet amyloid agents in the clinic. We show that aspirin, even in 20-fold excess, has no effect on the kinetics of amyloid formation by amylin as judged by thioflavin-T binding, right angle light scattering, and transmission electron microscopy, nor does it alter the morphology of resulting amyloid fibrils. Aspirin showed no ability to disaggregate preformed amylin amyloid fibrils under the conditions of these studies, 25 °C and pH 7.4. Ketoprofen is similarly ineffective at inhibiting amylin amyloid formation. The compounds do, however, interfere with circular dichroism- and Congo Red-based assays of amylin amyloid formation. This study highlights the importance of using multiple methods to follow amyloid formation when screening inhibitors.

Original languageEnglish
Pages (from-to)1632-1637
Number of pages6
JournalACS Chemical Biology
Volume9
Issue number7
DOIs
Publication statusPublished - 2014 Jul 18

Fingerprint

Ketoprofen
Medical problems
Amyloid
Islet Amyloid Polypeptide
Aspirin
Amyloidosis
Congo Red
Transplants
Cell death
Light transmission
Circular Dichroism
Transmission Electron Microscopy
Light scattering
Assays
Screening
Cell Death
Anti-Inflammatory Agents
Hormones
Transmission electron microscopy
Inflammation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Aspirin, diabetes, and amyloid : Re-examination of the inhibition of amyloid formation by aspirin and ketoprofen. / Tu, Ling Hsien; Noor, Harris; Cao, Ping; Raleigh, Daniel P.

In: ACS Chemical Biology, Vol. 9, No. 7, 18.07.2014, p. 1632-1637.

Research output: Contribution to journalArticle

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