Hyposmotic shock stimulates insulin secretion by two distinct mechanisms. Studies with the betaHC9 cell.
Hyposmotic shock stimulates insulin secretion by two distinct mechanisms. Studies with the betaHC9 cell.
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低渗性休克通过两种不同的机制刺激胰岛素分泌。
DOI：
10.1152/ajpendo.00176.2001
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Sharp,GeoffreyWG
中科院分区：
文献类型：
--
作者：
Straub,SusanneG;Daniel,Samira;Sharp,GeoffreyWG
将β HC 9细胞暴露于通过减少25 mM NaCl而制成低渗的Krebs-Ringer碳酸氢盐-HEPES缓冲液（KRBH）中，可迅速刺激胰岛素释放。刺激是短暂的，和释放率恢复到基础水平后10分钟。响应类似于葡萄糖刺激的胰岛素释放的第一阶段。如果通过加入等渗量的山梨醇补偿NaCl的减少，则不会发生反应，因此释放刺激是由于渗透压变化而不是NaCl的减少。低渗性休克使KRBH在有或无Ca ~（2+）时释放胰岛素。L型Ca 2+通道阻滞剂尼群地平可抑制正常KRBH的反应，但对无Ca 2+的KRBH没有影响，尽管后者的反应比存在细胞外Ca 2+的情况下更大。用calciseptine也获得了类似的数据，calciseptine也阻断了L型通道。T-型钙通道阻滞剂氟桂利嗪没有影响，是氯通道阻滞剂DIDS。在平行研究中，监测了含胰岛素颗粒的易释放池。靶SNARE蛋白突触融合蛋白的免疫沉淀和囊泡SNARE VAMP-2的免疫共沉淀被用作易释放颗粒库的指示剂。低渗休克后，在细胞外Ca 2+的存在下，VAMP-2 coimmunoprecipitated抗体对syntaxin的量大大减少与对照组相比。因此，在这些条件下，低渗休克刺激含胰岛素颗粒的易释放池的胞吐作用。没有这样的减少被认为是在细胞外Ca 2+的情况下。总之，在重新检查低渗性休克在存在和不存在Ca 2+（培养基中有EGTA）的情况下对胰岛素分泌的影响后，很明显，在这些条件下有两种不同的机制起作用。此外，这两种机制可能与两种不同的含胰岛素颗粒池的释放有关。
Exposure of βHC9 cells to a Krebs-Ringer bicarbonate-HEPES buffer (KRBH) made hypotonic by a reduction of 25 mM NaCl resulted in a prompt stimulation of insulin release. The stimulation was transient, and release rates returned to basal levels after 10 min. The response resembles that of the first phase of glucose-stimulated insulin release. The response did not occur if the reduction in NaCl was compensated for by the addition of an equivalent osmolar amount of sorbitol, so the stimulation of release was due to the osmolarity change and not the reduction in NaCl. The hyposmotic shock released insulin in KRBH with or without Ca2+. The L-type Ca2+channel blocker nitrendipine inhibited the response in normal KRBH but had no effect in KRBH without Ca2+despite the latter response being larger than in the presence of extracellular Ca2+. Similar data were obtained with calciseptine, which also blocks L-type channels. The T-type Ca2+channel blocker flunarizine was without effect, as was the chloride channel blocker DIDS. In parallel studies, the readily releasable pool of insulin-containing granules was monitored. Immunoprecipitation of the target-SNARE protein syntaxin and co-immunoprecipitation of the vesicle-SNARE VAMP-2 was used as an indicator of the readily releasable granule pool. After hypotonic shock in the presence of extracellular Ca2+, the amount of VAMP-2 coimmunoprecipitated by antibodies against syntaxin was much reduced compared with controls. Therefore, under these conditions, hypotonic shock stimulates exocytosis of the readily releasable pool of insulin-containing granules. No such reduction was seen in the absence of extracellular Ca2+. In conclusion, after reexamination of the effect of hyposmotic shock on insulin secretion in the presence and absence of Ca2+(with EGTA in the medium), it is clear that two different mechanisms are operative under these conditions. Moreover, these two mechanisms may be associated with the release of two distinct pools of insulin-containing granules.
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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DOI：
--
发表时间：
1997
期刊：
Life Science
影响因子：
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作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
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