Newly synthesized proinsulin/insulin and stored insulin are released from pancreatic B cells predominantly via a regulated, rather than a constitutive, pathway.
Newly synthesized proinsulin/insulin and stored insulin are released from pancreatic B cells predominantly via a regulated, rather than a constitutive, pathway.
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DOI：
10.1083/jcb.105.1.145
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发表时间：
1987-07
期刊：
影响因子：
--
通讯作者：
Halban PA
中科院分区：
文献类型：
--
作者：
Rhodes CJ;Halban PA
以胰腺B细胞为模型，比较新合成的原激素和储存的激素的释放。在基础和刺激葡萄糖浓度超过180分钟的情况下，从分离的大鼠胰岛监测新合成的胰岛素原/胰岛素（以[3H]亮氨酸标记）的分泌和储存的总免疫反应性胰岛素。180分钟后，16.7 mM葡萄糖释放15%的胰岛储存胰岛素，而2.8 mM葡萄糖释放2%。延迟30分钟后，检测新合成（标记）胰岛素原和胰岛素的释放；从60分钟开始，16.7 mM葡萄糖对这种释放的刺激高达11倍。180分钟时，在16.7 mM葡萄糖和2.8 mM葡萄糖条件下，分别释放60%和6%的初始胰岛胰岛素原。释放的新合成激素相对于胰岛内物质的放射性比表明其优先释放。在两种葡萄糖浓度下，释放的标记产物的同位素富集程度相似。定量高效液相色谱分析表明，葡萄糖对细胞内胰岛素原向胰岛素转化没有影响；新合成的胰岛素原和胰岛素的释放均对葡萄糖刺激敏感；90%的新合成激素以胰岛素的形式释放；只有0.5%的胰岛素原以不依赖葡萄糖的方式快速释放（在30 - 60分钟之间）。由此得出结论，释放激素的大部分，无论是旧的还是新的，加工的还是未加工的，都是通过受调节的途径释放的，因此，通过构成途径释放的少量（少于1%）不能解释B细胞优先释放新形成的产物。
The pancreatic B cell has been used as a model to compare the release of newly synthesized prohormone/hormone with that of stored hormone. Secretion of newly synthesized proinsulin/insulin (labeled with [3H]leucine during a 5-min pulse) and stored total immunoreactive insulin was monitored from isolated rat pancreatic islets at basal and stimulatory glucose concentrations over 180 min. By 180 min, 15% of the islet content of stored insulin was released at 16.7 mM glucose compared with 2% at 2.8 mM glucose. After a 30-min lag period, release of newly synthesized (labeled) proinsulin and insulin was detected; from 60 min onwards this release was stimulated up to 11-fold by 16.7 mM glucose. At 180 min, 60% of the initial islet content of labeled proinsulin was released at 16.7 mM glucose and 6% at 2.8 mM glucose. Specific radioactivity of the released newly synthesized hormone relative to that of material in islets indicated its preferential release. A similar degree of isotopic enrichment of released, labeled products was observed at both glucose concentrations. Quantitative HPLC analysis of labeled products indicated that glucose had no effect on intracellular proinsulin to insulin conversion; release of both newly synthesized proinsulin and insulin was sensitive to glucose stimulation; 90% of the newly synthesized hormone was released as insulin; and only 0.5% of proinsulin was rapidly released (between 30 and 60 min) in a glucose-independent fashion. It is thus concluded that the major portion of released hormone, whether old or new, processed or unprocessed, is directed through the regulated pathway, and therefore the small (less than 1%) amount released via a constitutive pathway cannot explain the preferential release of newly formed products from the B cell.
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DOI：
10.1083/jcb.99.1.97
发表时间：
1984-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Green R;Shields D
通讯作者：
Shields D
影响因子：
64.8
作者：
MOORE, HP;GUMBINER, B;KELLY, RB
通讯作者：
KELLY, RB
影响因子：
7.8
作者：
ALLAN, VJ;KREIS, TE
通讯作者：
KREIS, TE
影响因子：
4.8
作者：
BERNE, C
通讯作者：
BERNE, C
影响因子：
2.9
作者：
ELKS, ML;YOUNGBLOOD, WW;KIZER, JS
通讯作者：
KIZER, JS