Microtubules and Gαo-signaling modulate the preferential secretion of young insulin secretory granules in islet β cells via independent pathways.
Microtubules and Gαo-signaling modulate the preferential secretion of young insulin secretory granules in islet β cells via independent pathways.
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DOI：
10.1371/journal.pone.0241939
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Gu G
中科院分区：
文献类型：
--
作者：
Hu R;Zhu X;Yuan M;Ho KH;Kaverina I;Gu G
为了维持功能，每个胰岛β细胞始终保持数千个胰岛素分泌颗粒（SG）。葡萄糖刺激诱导这些SG的一小部分的分泌，同时促进SG生物合成以维持该储备。这些过程的失败，通常由持续的高胰岛素输出引起，导致2型糖尿病。有趣的是，年轻的胰岛素SG更有可能在葡萄糖刺激的胰岛素分泌（GSIS）期间分泌，原因不明，而较老的SG往往失去释放能力并被降解。在这里，我们研究微管（MT）和Gα o信号在调节年轻与老年SGs的优先分泌中的作用。我们发现MT失稳和Gαo失活导致更多的SG定位在质膜（PM）附近，尽管GSIS水平较高，SG生物合成减少。有趣的是，MT失稳或Gα o失活导致老年SG的分泌概率更高，而两者结合对增强GSIS具有累加效应。最后，Gαo失活不会明显破坏β细胞MT网络。这些结果表明，Gαo和MT可以通过基本平行的途径调节年轻胰岛素SG的优先释放。
For sustainable function, each pancreatic islet β cell maintains thousands of insulin secretory granules (SGs) at all times. Glucose stimulation induces the secretion of a small portion of these SGs and simultaneously boosts SG biosynthesis to sustain this stock. The failure of these processes, often induced by sustained high-insulin output, results in type 2 diabetes. Intriguingly, young insulin SGs are more likely secreted during glucose-stimulated insulin secretion (GSIS) for unknown reasons, while older SGs tend to lose releasability and be degraded. Here, we examine the roles of microtubule (MT) and Gαo-signaling in regulating the preferential secretion of young versus old SGs. We show that both MT-destabilization and Gαo inactivation results in more SGs localization near plasma membrane (PM) despite higher levels of GSIS and reduced SG biosynthesis. Intriguingly, MT-destabilization or Gαo-inactivation results in higher secretion probabilities of older SGs, while combining both having additive effects on boosting GSIS. Lastly, Gαo inactivation does not detectably destabilize the β-cell MT network. These findings suggest that Gαo and MT can modulate the preferential release of younger insulin SGs via largely parallel pathways.