Cytokine-mediated changes in K(+) channel activity promotes an adaptive Ca(2+) response that sustains β-cell insulin secretion during inflammation.
Cytokine-mediated changes in K(+) channel activity promotes an adaptive Ca(2+) response that sustains β-cell insulin secretion during inflammation.
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细胞因子介导的K（+）通道活性的变化促进了自适应Ca（2+）反应，该反应在炎症过程中维持β细胞胰岛素分泌。
DOI：
10.1038/s41598-018-19600-x
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发表时间：
2018-01-18
影响因子：
4.6
通讯作者：
Jacobson DA
中科院分区：
文献类型：
--
作者：
Dickerson MT;Bogart AM;Altman MK;Milian SC;Jordan KL;Dadi PK;Jacobson DA
低度炎症时存在的细胞因子会导致β细胞功能障碍和糖尿病。细胞因子信号转导干扰β细胞葡萄糖刺激的钙内流(GSCI)和内质网(ER)钙离子([Ca+]ER)的处理，导致葡萄糖刺激的胰岛素分泌(GSI)减少。然而，细胞因子介导的离子通道活性的改变改变β细胞的钙离子处理仍然未知。在这里，我们研究了K+电流在细胞因子介导的β细胞功能障碍中的作用。控制细胞内钙([Ca~(2+)]_i)振荡终止的K慢电流在细胞因子作用下减少。其结果是，[Ca~(2+)]i和电振荡加速。细胞因子暴露也增加了基础胰岛[Ca~(2+)]i，降低了GSCI。细胞因子对Talk-1钾电流的影响也被检测为Talk-1通过促进[Ca~(2+)]ER释放而介导Klow。细胞因子暴露降低KCNK16转录丰度和相关的Talk-1蛋白表达，增加[Ca~(2+)]ER存储，同时维持第二期GSCI和GSIS。这种适应性钙反应在Talk-1 KO胰岛中缺失，表现为第二时相GSCI减少和GSIS减少。这些发现表明，在低度炎症过程中，Klow和Talk-1电流在改变β细胞的钙处理和电活动中发挥重要作用。这些结果还表明，细胞因子介导的Talk-1的减少通过促进β-细胞内钙含量的增加来维持GSI，从而对GSI-细胞起到急性保护作用。
Cytokines present during low-grade inflammation contribute to β-cell dysfunction and diabetes. Cytokine signaling disrupts β-cell glucose-stimulated Ca2+ influx (GSCI) and endoplasmic reticulum (ER) Ca2+ ([Ca2+]ER) handling, leading to diminished glucose-stimulated insulin secretion (GSIS). However, cytokine-mediated changes in ion channel activity that alter β-cell Ca2+ handling remain unknown. Here we investigated the role of K+ currents in cytokine-mediated β-cell dysfunction. Kslow currents, which control the termination of intracellular Ca2+ ([Ca2+]i) oscillations, were reduced following cytokine exposure. As a consequence, [Ca2+]i and electrical oscillations were accelerated. Cytokine exposure also increased basal islet [Ca2+]i and decreased GSCI. The effect of cytokines on TALK-1 K+ currents were also examined as TALK-1 mediates Kslow by facilitating [Ca2+]ER release. Cytokine exposure decreased KCNK16 transcript abundance and associated TALK-1 protein expression, increasing [Ca2+]ER storage while maintaining 2nd phase GSCI and GSIS. This adaptive Ca2+ response was absent in TALK-1 KO islets, which exhibited decreased 2nd phase GSCI and diminished GSIS. These findings suggest that Kslow and TALK-1 currents play important roles in altered β-cell Ca2+ handling and electrical activity during low-grade inflammation. These results also reveal that a cytokine-mediated reduction in TALK-1 serves an acute protective role in β-cells by facilitating increased Ca2+ content to maintain GSIS.
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影响因子：
2.8
作者：
Al-Shukaili A;Al-Ghafri S;Al-Marhoobi S;Al-Abri S;Al-Lawati J;Al-Maskari M
通讯作者：
Al-Maskari M
影响因子：
3.7
作者：
Dickerson MT;Vierra NC;Milian SC;Dadi PK;Jacobson DA
通讯作者：
Jacobson DA
影响因子：
--
作者：
Bertram, Richard;Sherman, Arthur;Satin, Leslie S.
通讯作者：
Satin, Leslie S.
DOI：
10.1016/j.bbrc.2004.01.137
发表时间：
2004-03-19
影响因子：
3.1
作者：
Kang, DW;Kim, D
通讯作者：
Kim, D
影响因子：
5.5
作者：
Jacobson, David A.;Mendez, Felipe;Philipson, Louis H.
通讯作者：
Philipson, Louis H.