Oxidative stress is induced by islet amyloid formation and time-dependently mediates amyloid-induced beta cell apoptosis.
Oxidative stress is induced by islet amyloid formation and time-dependently mediates amyloid-induced beta cell apoptosis.
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DOI：
10.1007/s00125-008-1255-x
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发表时间：
2009-04
期刊：
影响因子：
8.2
通讯作者：
Kahn, S. E.
中科院分区：
文献类型：
--
作者：
Zraika, S.;Hull, R. L.;Udayasankar, J.;Aston-Mourney, K.;Subramanian, S. L.;Kisilevsky, R.;Szarek, W. A.;Kahn, S. E.
2 型糖尿病中的胰岛淀粉样蛋白会导致 β 细胞质量和功能丧失。由于胰岛容易受到氧化应激诱导的毒性的影响，我们试图确定胰岛淀粉样蛋白的形成是否与氧化应激的诱导有关。将人胰岛淀粉样蛋白多肽转基因和非转基因小鼠胰岛在有或没有抗氧化剂N-乙酰基-L-半胱氨酸(NAC)或淀粉样蛋白抑制剂刚果红的情况下培养48或144小时。测量淀粉样蛋白沉积、活性氧（ROS）产生、β细胞凋亡以及胰岛素分泌、含量和mRNA。 48小时后，淀粉样蛋白沉积与ROS水平升高和β细胞凋亡增加相关，但胰岛素分泌、含量或mRNA表达没有变化。抗氧化治疗可阻止 ROS 的升高，但不能阻止淀粉样蛋白的形成或 β 细胞凋亡。相反，抑制淀粉样蛋白形成可以防止氧化应激和β细胞凋亡的诱导。 144小时后，淀粉样蛋白沉积进一步增加，并与ROS水平升高、β细胞凋亡增加和胰岛素含量降低相关。此时，抗氧化治疗和抑制淀粉样蛋白形成均能有效降低 ROS 水平、淀粉样蛋白形成和 β 细胞凋亡。抑制淀粉样蛋白的形成也会增加胰岛素含量。胰岛淀粉样蛋白的形成会诱导氧化应激，短期内不会介导β细胞凋亡，但从长远来看可能会反馈进一步加剧淀粉样蛋白的形成并导致β细胞凋亡。
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. Human islet amyloid polypeptide transgenic and non-transgenic mouse islets were cultured for 48 or 144 hours 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. After 48 hours, amyloid deposition was associated with increased ROS levels and increased beta cell apoptosis, but no change in insulin secretion, content or mRNA expression. Antioxidant treatment prevented the rise in ROS but did not prevent amyloid formation or beta cell apoptosis. In contrast, inhibition of amyloid formation prevented both the induction of oxidative stress and beta cell apoptosis. After 144 hours, amyloid deposition was further increased and was associated with increased ROS levels, increased beta cell apoptosis and decreased insulin content. At this time point, both 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. 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.
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影响因子：
3.5
作者：
BETSHOLTZ, C;CHRISTMANSSON, L;WESTERMARK, P
通讯作者：
WESTERMARK, P
影响因子：
7.7
作者：
DALESSIO, DA;VERCHERE, CB;ENSINCK, JW
通讯作者：
ENSINCK, JW
影响因子：
4.8
作者：
Green, JD;Goldsbury, C;Aebi, U
通讯作者：
Aebi, U
DOI：
10.1073/pnas.84.23.8628
发表时间：
1987-12-01
影响因子：
11.1
作者：
COOPER, GJS;WILLIS, AC;REID, KBM
通讯作者：
REID, KBM
影响因子：
3.5
作者：
Kooptiwut, S;Kebede, M;Andrikopoulos, S
通讯作者：
Andrikopoulos, S