Accounting for near-normal glucose sensitivity in Kir6.2[AAA] transgenic mice.
Accounting for near-normal glucose sensitivity in Kir6.2[AAA] transgenic mice.
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解释 Kir6.2[AAA] 转基因小鼠接近正常的葡萄糖敏感性。
DOI：
10.1016/j.bpj.2009.07.060
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发表时间：
2009
影响因子：
3.4
通讯作者：
Sherman,Arthur
中科院分区：
文献类型：
--
作者：
Tsaneva-Atanasova,Krasimira;Sherman,Arthur
Kir6.2[AAA]转基因小鼠胰岛表现出嵌合现象，约70%的β细胞具有非功能性ATP敏感性钾（KATP）通道，而其余的具有正常的KATP功能。尽管这种急剧减少，葡萄糖的剂量-反应曲线仅移动了0.02 mM. We使用以前发表的数学模型，其中KATP电导增加的上升，通过间接影响代谢的胞质钙，调查细胞如何可以补偿损失的KATP电导。补偿是有利的假设，只有一小部分的KATP通道是开放的振荡过程中，这使得它很容易上调开放分数通过钙的适度升高。我们进一步表明，需要膜电位和钙离子的强间隙连接偶联来克服这些马赛克胰岛中细胞特性的明显异质性。
Kir6.2[AAA] transgenic mouse islets exhibit mosaicism such that ∼70% of theβ-cells have nonfunctional ATP-sensitive potassium (KATP) channels, whereas the remainder have normal KATPfunction. Despite this drastic reduction, the glucose dose-response curve is only shifted by ∼2 mM. We use a previously published mathematical model, in which KATPconductance is increased by rises in cytosolic calcium through indirect effects on metabolism, to investigate how cells could compensate for the loss of KATPconductance. Compensation is favored by the assumption that only a small fraction of KATPchannels are open during oscillations, which renders it easy to upregulate the open fraction via a modest elevation of calcium. We show further that strong gap-junctional coupling of both membrane potential and calcium is needed to overcome the stark heterogeneity of cell properties in these mosaic islets.