Regulation of Glucose-Dependent Golgi-Derived Microtubules by cAMP/EPAC2 Promotes Secretory Vesicle Biogenesis in Pancreatic β Cells.

Trogden KP, Zhu X, Lee JS, Wright CVE, Gu G, Kaverina I
Curr Biol. 2019 29 (14): 2339-2350.e5

PMID: 31303487 · PMCID: PMC6698911 · DOI:10.1016/j.cub.2019.06.032

The microtubule (MT) network is an essential regulator of insulin secretion from pancreatic β 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 β-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 β-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.

Copyright © 2019 Elsevier Ltd. All rights reserved.

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