Small interfering RNA-mediated suppression of proislet amyloid polypeptide expression inhibits islet amyloid formation and enhances survival of human islets in culture
Diabetes, ISSN: 0012-1797, Vol: 57, Issue: 11, Page: 3045-3055
2008
- 44Citations
- 37Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations44
- Citation Indexes44
- CrossRef44
- 41
- Captures37
- Readers37
- 37
Article Description
OBJECTIVE-Islet amyloid, formed by aggregation of the β-cell peptide islet amyloid polypeptide (IAPP; amylin), is a pathological characteristic of pancreatic islets in type 2 diabetes. Toxic IAPP aggregates likely contribute to the progressive loss of p-cells in this disease. We used cultured human islets as an ex vivo model of amyloid formation to investigate whether suppression of proIAPP expression would inhibit islet amyloid formation and enhance β-cell survival and function. RESEARCH DESIGN AND METHODS-Islets from cadaveric organ donors were transduced with a recombinant adenovirus expressing a short interfering RNA (siRNA) designed to suppress human proIAPP (Ad-hProIAPP-siRNA), cultured for 10 days, and then assessed for the presence of islet amyloid, β-cell apoptosis, and β-cell function. RESULTS-Thioflavine S-positive amyloid deposits were clearly present after 10 days of culture. Transduction with Ad-hProIAPP- siRNA reduced proIAPP expression by 75% compared with nontransduced islets as assessed by Western blot analysis of islet lysates 4 days after transduction. siRNA-mediated inhibition of IAPP expression decreased islet amyloid area by 63% compared with nontransduced cultured islets. Cell death assessed by transferase-mediated dUTP nick-end labeling staining was decreased by 50% in transduced cultured human islets, associated with a significant increase in islet insulin content (control, 100 ± 4 vs. +Ad-siRNA, 153 ± 22%, P < 0.01) and glucose-stimulated insulin secretion (control, 222 ± 33 vs. +Ad-siRNA, 285 ± 21 percent basal, P < 0.05). CONCLUSIONS-These findings demonstrate that inhibition of IAPP synthesis prevents amyloid formation and β-cell death in cultured human islets. Inhibitors of IAPP synthesis may have therapeutic value in type 2 diabetes. 2008. © 2008 by the American Diabetes Association.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=58149343826&origin=inward; http://dx.doi.org/10.2337/db08-0485; http://www.ncbi.nlm.nih.gov/pubmed/18694973; https://diabetesjournals.org/diabetes/article/57/11/3045/13399/Small-Interfering-RNA-Mediated-Suppression-of; https://dx.doi.org/10.2337/db08-0485
American Diabetes Association
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