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首页> 外文期刊>Cell and Tissue Research >Chromogranin A regulates vesicle storage and mitochondrial dynamics to influence insulin secretion
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Chromogranin A regulates vesicle storage and mitochondrial dynamics to influence insulin secretion

机译：Chromogranin A调节囊泡储存和线粒体动力学，以影响胰岛素分泌

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摘要

Chromogranin A (CgA) is a prohormone and a granulogenic factor that regulates secretory pathways in neuroendocrine tissues. In beta-cells of the endocrine pancreas, CgA is a major cargo in insulin secretory vesicles. The impact of CgA deficiency on the formation and exocytosis of insulin vesicles is yet to be investigated. In addition, no literature exists on the impact of CgA on mitochondrial function in beta-cells. Using three different antibodies, we demonstrate that CgA is processed to vasostatin- and catestatin-containing fragments in pancreatic islet cells. CgA deficiency in Chga-KO islets leads to compensatory overexpression of chromogranin B, secretogranin II, SNARE proteins and insulin genes, as well as increased insulin protein content. Ultrastructural studies of pancreatic islets revealed that Chga-KO beta-cells contain fewer immature secretory granules than wild-type (WT) control but increased numbers of mature secretory granules and plasma membrane-docked vesicles. Compared to WT control, CgA-deficient beta-cells exhibited increases in mitochondrial volume, numerical densities and fusion, as well as increased expression of nuclear encoded genes (Ndufa9, Ndufs8, Cyc1 and Atp5o). These changes in secretory vesicles and the mitochondria likely contribute to the increased glucose-stimulated insulin secretion observed in Chga-KO mice. We conclude that CgA is an important regulator for coordination of mitochondrial dynamics, secretory vesicular quanta and GSIS for optimal secretory functioning of beta-cells, suggesting a strong, CgA-dependent positive link between mitochondrial fusion and GSIS.
机译：Chromogranin A（CGA）是预甲型仑和调节神经内分泌组织中的分泌途径的颗粒原性因子。在内分泌胰腺的β细胞中，CGA是胰岛素分泌囊泡的主要货物。 CGA缺乏对胰岛素囊泡形成和外尿精的影响尚未研究。此外，CGA对β细胞中线粒体功能的影响不存在文献。使用三种不同的抗体，我们证明CGA在胰岛细胞中加工到含血管抑制素和含磷酸汀的碎片。 CGA-Ko胰岛的CGA缺乏导致Chromogranin B，秘密蛋白II，纳雷蛋白和胰岛素基因的补偿过表达，以及胰岛素蛋白质含量增加。胰岛的超微结构研究表明，CHGA-KOβ细胞含有比野生型（WT）对照的不成熟的分泌颗粒，但成熟分泌颗粒和血浆膜对接囊泡的数量增加。与WT控制相比，CGA缺陷型β细胞表现出线粒体体积，数值密度和融合的增加，以及增加核编码基因的表达（NDUFA9，NDUFS8，CYC1和ATP5O）。这些分泌囊泡和线粒体的变化可能有助于在CHGA-KO小鼠中观察到的增加的葡萄糖刺激的胰岛素分泌。我们得出结论，CGA是用于协调线粒体动力学，分泌囊泡Quanta和GSIS的重要调节因子，以获得β细胞的最佳分泌功能，表明线粒体融合和GSIS之间的强，CGA依赖性阳性联系。

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