Cellular Autophagy in α Cells Plays a Role in the Maintenance of Islet Architecture
Cellular Autophagy in α Cells Plays a Role in the Maintenance of Islet Architecture
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DOI：
10.1210/js.2019-00075
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发表时间：
2019-11-01
影响因子：
4.1
通讯作者：
Watada, Hirotaka
中科院分区：
文献类型：
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作者：
Himuro, Miwa;Miyatsuka, Takeshi;Watada, Hirotaka
自噬通过降解亚细胞内受损的细胞器和成分，在细胞内质量控制中发挥关键作用。尽管自噬对于维持胰岛中的β细胞功能至关重要，但细胞自噬如何影响胰高血糖素分泌α细胞的稳态和功能仍不清楚。为了研究自噬在α细胞中的作用，我们产生了缺乏Atg7的突变小鼠模型，Atg7是自噬体形成的关键分子，特别是在α细胞中。组织学分析表明，更多的胰高血糖素阳性细胞，与多层结构，在胰岛下Atg7缺陷，虽然代谢概况，如体重，血糖，血浆胰高血糖素水平之间的Atg7缺陷小鼠和对照同窝出生。与我们先前发现Atg7缺陷抑制β细胞增殖一致，Atg7缺陷α细胞的细胞增殖受到抑制。这些发现表明，α细胞自噬在维持α细胞面积和正常胰岛结构中起作用，但似乎不利于代谢稳态。版权所有（C）2019内分泌学会
Autophagy is known to play a pivotal role in intracellular quality control through the degradation of subcellular damaged organelles and components. Whereas autophagy is essential for maintaining beta-cell function in pancreatic islets, it remains unclear as to how the cellular autophagy affects the homeostasis and function of glucagon-secreting alpha cells. To investigate the role of autophagy in alpha cells, we generated a mutant mouse model lacking Atg7, a key molecule for autophagosome formation, specifically in alpha cells. Histological analysis demonstrated more glucagon-positive cells, with a multilayered structure, in the islets under Atg7 deficiency, although metabolic profiles, such as body weight, blood glucose, and plasma glucagon levels were comparable between Atg7-deficient mice and control littermates. Consistent with our previous findings that Atg7 deficiency suppressed beta-cell proliferation, cellular proliferation was suppressed in Atg7-deficient alpha cells. These findings suggest that alpha-cell autophagy plays a role in maintaining alpha-cell area and normal islet architecture but appears to be dispensable for metabolic homeostasis. Copyright (C) 2019 Endocrine Society