Pancreatic β-cells from obese-hyperglycemic mice are characterized by excessive firing of cytoplasmic Ca2+ transients
Pancreatic β-cells from obese-hyperglycemic mice are characterized by excessive firing of cytoplasmic Ca2+ transients
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DOI：
10.1385/endo:15:1:073
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发表时间：
2001-06-01
期刊：
影响因子：
3.7
通讯作者：
Grapengiesser, E
中科院分区：
文献类型：
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作者：
Ahmed, M;Grapengiesser, E
来自肥胖-高血糖（ob/ob）小鼠的胰腺β细胞被广泛用于研究胰岛素释放的机制，包括其通过细胞质Ca 2+浓度（[Ca 2 +]（i））的调节。在这项研究中，我们使用双波长显微荧光法和指示剂fura-2比较了从ob/ob小鼠和瘦小鼠分离的单个β细胞中[Ca 2 +]（i）的变化。葡萄糖引起的慢振荡的频率、振幅和半宽没有差异。来自肥胖小鼠的大多数β细胞对10 mM咖啡因有反应，将振荡转化为[Ca 2 +]（i）的持续升高，这一过程被兰尼定抵消。来自肥胖小鼠的β细胞的特征在于大量产生[Ca 2 +]（i）瞬变，其在胰高血糖素存在下数量增加。当瘦素以低至1 nM的浓度加入时，瞬变变得不那么频繁。这表明，[Ca 2 +]（i）瞬变在ob/ob小鼠中的过度放电是由于缺乏瘦素，并通过激活磷脂酶C信号通路介导的。
Pancreatic beta -cells from obese-hyperglycemic (ob/ob) mice are widely used for studying the mechanisms of insulin release, including its regulation by the cytoplasmic Ca2+ concentration ([Ca2+](i)). In this study, we compared changes of [Ca2+](i) in single beta -cells isolated from ob/ob mice with those from lean mice using dual-wavelength microfluorometry and the indicator fura-2. There were no differences in the frequency, amplitude, and half-width of the slow oscillations induced by glucose. Most beta -cells from the obese mice responded to 10 mM caffeine with transformation of the oscillations into sustained elevation of [Ca2+](i), a process counteracted by ryanodine. The beta -cells from the obese mice were characterized by ample generation of [Ca2+](i) transients, which increased in number in the presence of glucagon. The transients became less frequent when leptin was added at a concentration as low as 1 nM. It is suggested that the excessive firing of [Ca2+](i) transients in the ob/ob mice is owing to the absence of leptin and is mediated by activation of the phospholipase C signaling pathway.