First Author | Hu R | Year | 2021 |
Journal | PLoS One | Volume | 16 |
Issue | 7 | Pages | e0241939 |
PubMed ID | 34292976 | Mgi Jnum | J:308490 |
Mgi Id | MGI:6728009 | Doi | 10.1371/journal.pone.0241939 |
Citation | Hu R, et al. (2021) Microtubules and Galphao-signaling modulate the preferential secretion of young insulin secretory granules in islet beta cells via independent pathways. PLoS One 16(7):e0241939 |
abstractText | For sustainable function, each pancreatic islet beta 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 Galphao-signaling in regulating the preferential secretion of young versus old SGs. We show that both MT-destabilization and Galphao inactivation results in more SGs localization near plasma membrane (PM) despite higher levels of GSIS and reduced SG biosynthesis. Intriguingly, MT-destabilization or Galphao-inactivation results in higher secretion probabilities of older SGs, while combining both having additive effects on boosting GSIS. Lastly, Galphao inactivation does not detectably destabilize the beta-cell MT network. These findings suggest that Galphao and MT can modulate the preferential release of younger insulin SGs via largely parallel pathways. |