Heterogeneity of autophagic status in pancreatic β cells under metabolic stress.
Heterogeneity of autophagic status in pancreatic β cells under metabolic stress.
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DOI：
10.1016/j.bbrc.2018.01.070
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发表时间：
2018-02
影响因子：
3.1
通讯作者：
Mai Kamitani;T. Miyatsuka;Masaki Miura;K. Azuma;Luka Suzuki;Miwa Himuro;Takehiro Katahira;Y. Nishida;Y. Fujitani;H. Watada
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文献类型：
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作者：
Mai Kamitani;T. Miyatsuka;Masaki Miura;K. Azuma;Luka Suzuki;Miwa Himuro;Takehiro Katahira;Y. Nishida;Y. Fujitani;H. Watada
β细胞中的自噬已被证明在细胞内稳态和糖耐量异常的进展中起着关键作用。虽然体内和体外的代谢应激都会影响自噬活性，但目前还不清楚每个β细胞的自噬状态与其邻近细胞的不同程度。为了解决这个问题，可以将每个β细胞的自噬状态可视化为绿色荧光点的gfp-lc3报告鼠与肥胖的糖尿病db/db鼠杂交。绿色荧光斑点在GFP-LC3小鼠胰岛中的成像显示，β细胞是一个异质性群体，因为每个细胞中GFP-LC3斑点的密度是不同的。此外，GFP-LC3；db/db小鼠的变异性比非糖尿病GFP-LC3；db/+小鼠更大。此外，当用小剂量的S961处理GFP-LC3小鼠时，S961拮抗胰岛素信号而不会引起明显的高血糖，具有高密度GFP点状的β细胞的数量增加，这表明胰岛素抵抗影响自噬状态不依赖于血糖水平。这些结果表明，代谢应激下的胰腺β细胞在自噬状态方面是异质性的，这为深入了解每个β细胞的细胞动力学而不是整个β细胞群提供了洞察力。
Autophagy in β cells has been demonstrated to play a pivotal role in cellular homeostasis and the progression of glucose intolerance. Although autophagic activity is affected by metabolic stress both in vivo and in vitro, it remains unclear as to what extent the autophagic status in each β cell is different from its neighboring cells. To address this question, GFP-LC3 reporter mice, which can visualize the autophagic status of each β cell as green-fluorescent puncta, were crossed with obese diabetic db/db mice. Imaging of green-fluorescent puncta in the islets of GFP-LC3 mice revealed that β cells are a heterogeneous population, as the density of GFP-LC3 puncta in each cell was variable. Furthermore, the variability was greater in GFP-LC3; db/db mice than in non-diabetic GFP-LC3; db/+ mice. Furthermore, when GFP-LC3 mice were treated with a low dose of S961, which antagonizes insulin signaling without inducing overt hyperglycemia, the number of β cells with a high density of GFP puncta was increased, suggesting that insulin resistance affects autophagic status independently of glucose profiles. These results suggest that pancreatic β cells under metabolic stress are heterogeneous regarding their autophagic status, which provides insights into the cellular dynamics of each β cell rather than the whole β-cell population.