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


Autoria(s): Zraika, S.; Hull, R. L.; Udayasankar, J.; Aston-Mourney, K.; Subramanian, S. L.; Kisilevsky, R.; Szarek, W. A.; Kahn, S. E.
Data(s)

01/01/2009

Resumo

<b>Aims/hypothesis</b> 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.<br /><br /><b>Methods </b>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.<br /><br /><b>Results </b>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.<br /><br /><b>Conclusions/interpretation </b>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.<br />

Identificador

http://hdl.handle.net/10536/DRO/DU:30047466

Idioma(s)

eng

Publicador

Springer

Relação

http://dro.deakin.edu.au/eserv/DU:30047466/aston-oxidativestress-2009.pdf

http://dx.doi.org/10.1007/s00125-008-1255-x

Direitos

2009, Springer-Verlag

Palavras-Chave #beta cell apoptosis #IAPP #insulin secretion #Islet amyloid #oxidative stress
Tipo

Journal Article