Details

Autor(en) / Beteiligte

• Potter, Kathryn J.
• Scrocchi, Louise A.
• Warnock, Garth L.
• Ao, Ziliang
• Younker, Marika A.
• Rosenberg, Lawrence
• Lipsett, Mark
• Verchere, C. Bruce
• Fraser, Paul E.

Titel

Amyloid inhibitors enhance survival of cultured human islets

Ist Teil von

• Biochimica et biophysica acta, 2009-06, Vol.1790 (6), p.566-574

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• Amyloid fibrils created by misfolding and aggregation of proteins are a major pathological feature in a variety of degenerative diseases. Therapeutic approaches including amyloid vaccines and anti-aggregation compounds in models of amyloidosis point to an important role for amyloid in disease pathogenesis. Amyloid deposits derived from the β-cell peptide islet amyloid polypeptide (IAPP or amylin) are a characteristic of type 2 diabetes and may contribute to loss of β-cells in this disease. We developed a cellular model of rapid amyloid deposition using cultured human islets and observed a correlation between fibril accumulation and β-cell death. A series of overlapping peptides derived from IAPP was generated. A potent inhibitor (ANFLVH) of human IAPP aggregation was identified. This inhibitory peptide prevented IAPP fibril formation in vitro and in human islet cultures leading to a striking increase in islet cell viability. These findings indicate an important contribution of IAPP aggregation to β-cell death in situ and point to therapeutic applications for inhibitors of IAPP aggregation in enhancing β-cell survival. Anti-amyloid compounds could potentially reduce the loss of β-cell mass in type 2 diabetes and maintain healthy human islet cultures for β-cell replacement therapies.