Sur1 knockout mice -: A model for KATP channel-independent regulation of insulin secretion
Sur1 knockout mice -: A model for KATP channel-independent regulation of insulin secretion
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DOI：
10.1074/jbc.275.13.9270
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发表时间：
2000-03-31
影响因子：
4.8
通讯作者：
Bryan, J
中科院分区：
文献类型：
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作者：
Seghers, V;Nakazaki, M;Bryan, J
Sur 1基因敲除小鼠β细胞缺乏K-ATP通道，并显示自发性Ca 2+动作电位，与婴儿期持续性高胰岛素血症低血糖患者相同，但小鼠血糖正常，除非受到压力。Sur 1（-/-）胰岛缺乏第一时相胰岛素分泌，并表现出葡萄糖刺激的第二相分泌减弱，第一时相的丧失导致轻度葡萄糖耐受不良，而胰岛素输出减少与观察到的新生儿高血糖症一致。K-ATP通道的丧失损害了葡萄糖浓度下降后恢复到基础分泌水平的速率。这导致空腹时低血糖增加，并导致非常早期的短暂新生儿低血糖。尽管婴儿期持续性高胰岛素血症性低血糖强调了K-ATP依赖性离子途径在控制胰岛素释放中的重要性，但Sur 1（-/-）动物为研究调节胰岛素分泌的K-ATP非依赖性途径提供了一种新的模型。
Sur1 knockout mouse beta-cells lack K-ATP channels and show spontaneous Ca2+ action potentials equivalent to those seen in patients with persistent hyperinsulinemic hypoglycemia of infancy, but the mice are normoglycemic unless stressed. Sur1(-/-) islets lack first phase insulin secretion and exhibit an attenuated glucose-stimulated second phase secretion, Loss of the first phase leads to mild glucose intolerance, whereas reduced insulin output is consistent with observed neonatal hyperglycemia. Loss of K-ATP channels impairs the rate of return to a basal secretory level after a fall in glucose concentration. This leads to increased hypoglycemia upon fasting and contributes to a very early, transient neonatal hypoglycemia. Whereas persistent hyperinsulinemic hypoglycemia of infancy underscores the importance of the K-ATP-dependent ionic pathway in control of insulin release, the Sur1(-/-) animals provide a novel model for study of K-ATP-independent pathways that regulate insulin secretion.