期刊
CURRENT BIOLOGY
卷 29, 期 14, 页码 2339-+出版社
CELL PRESS
DOI: 10.1016/j.cub.2019.06.032
关键词
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资金
- National Institutes of Health (NIH) [T32 DK07061, 1F32DK117529, R35-GM127098, R01DK65949, R01-DK106228]
- NIH [DK020593, CA68485, DK20593, DK58404, DK59637, EY08126, SEI10, 1sS10, 1S10OD018075, S10OD012324]
- Vanderbilt Ingram Cancer Center (NIH) [P30CA68485]
- Vanderbilt Digestive Disease Research Center (NIH) [DK058404]
The microtubule (MT) network is an essential regulator of insulin secretion from pancreatic beta cells, which is central to blood-sugar homeostasis. We find that when glucose metabolism induces insulin secretion, it also increases formation of Golgi-derived microtubules (GDMTs), notably with the same biphasic kinetics as insulin exocytosis. Furthermore, GDMT nucleation is controlled by a glucose signal-transduction pathway through cAMP and its effector EPAC2. Preventing new GDMT nucleation dramatically affects the pipeline of insulin production, storage, and release. There is an overall reduction of beta-cell insulin content, and remaining insulin becomes retained within the Golgi, likely because of stalling of insulin-granule budding. While not preventing glucose-induced insulin exocytosis, the diminished granule availability substantially blunts the amount secreted. Constant dynamic maintenance of the GDMT network is therefore critical for normal beta-cell physiology. Our study demonstrates that the biogenesis of post-Golgi carriers, particularly large secretory granules, requires ongoing nucleation and replenishment of the GDMT network.
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