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Oxidative stress is induced by islet amyloid formation and time-dependently mediates amyloid-induced beta cell apoptosis

Zraika, S., Hull, R. L., Udayasankar, J., Aston-Mourney, K., Subramanian, S. L., Kisilevsky, R., Szarek, W. A. and Kahn, S. E. 2009, Oxidative stress is induced by islet amyloid formation and time-dependently mediates amyloid-induced beta cell apoptosis, Diabetologia, vol. 52, no. 4, pp. 626-635, doi: 10.1007/s00125-008-1255-x.

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Title Oxidative stress is induced by islet amyloid formation and time-dependently mediates amyloid-induced beta cell apoptosis
Author(s) Zraika, S.
Hull, R. L.
Udayasankar, J.
Aston-Mourney, K.
Subramanian, S. L.
Kisilevsky, R.
Szarek, W. A.
Kahn, S. E.
Journal name Diabetologia
Volume number 52
Issue number 4
Start page 626
End page 635
Total pages 10
Publisher Springer
Place of publication Heidelberg, Germany
Publication date 2009
ISSN 0012-186X
1432-0428
Keyword(s) beta cell apoptosis
IAPP
insulin secretion
Islet amyloid
oxidative stress
Summary Aims/hypothesis Islet amyloid in type 2 diabetes contributes to loss of beta cell mass and function. Since islets are susceptible to oxidative stress-induced toxicity, we sought to determine whether islet amyloid formation is associated with induction of oxidative stress.

Methods Human islet amyloid polypeptide transgenic and non-transgenic mouse islets were cultured for 48 or 144 h with or without the antioxidant N-acetyl-l-cysteine (NAC) or the amyloid inhibitor Congo Red. Amyloid deposition, reactive oxygen species (ROS) production, beta cell apoptosis, and insulin secretion, content and mRNA were measured.

Results After 48 h, amyloid deposition was associated with increased ROS levels and increased beta cell apoptosis, but no change in insulin secretion, content or mRNA levels. Antioxidant treatment prevented the rise in ROS, but did not prevent amyloid formation or beta cell apoptosis. In contrast, inhibition of amyloid formation prevented the induction of oxidative stress and beta cell apoptosis. After 144 h, amyloid deposition was further increased and was associated with increased ROS levels, increased beta cell apoptosis and decreased insulin content. At this time-point, antioxidant treatment and inhibition of amyloid formation were effective in reducing ROS levels, amyloid formation and beta cell apoptosis. Inhibition of amyloid formation also increased insulin content.

Conclusions/interpretation Islet amyloid formation induces oxidative stress, which in the short term does not mediate beta cell apoptosis, but in the longer term may feed back to further exacerbate amyloid formation and contribute to beta cell apoptosis.
Language eng
DOI 10.1007/s00125-008-1255-x
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2009, Springer-Verlag
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047466

Document type: Journal Article
Collection: School of Medicine
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