Genetic ablation of p62/SQSTM1 demonstrates little effect on pancreatic β-cell function under autophagy deficiency
Genetic ablation of p62/SQSTM1 demonstrates little effect on pancreatic β-cell function under autophagy deficiency
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p62/SQSTM1 的基因消融表明自噬缺陷下对胰腺 β 细胞功能影响不大
DOI：
10.1016/j.bbrc.2022.04.092
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发表时间：
2022
影响因子：
3.1
通讯作者：
Watada Hirotaka
中科院分区：
文献类型：
--
作者：
Fukae Toshinaru;Miyatsuka Takeshi;Himuro Miwa;Wakabayashi Yuka;Iida Hitoshi;Aoyama Shuhei;Mita Tomoya;Ikeda Fuki;Haruna Hidenori;Takubo Noriyuki;Nishida Yuya;Shimizu Toshiaki;Watada Hirotaka
自噬通过降解受损的细胞器和成分在细胞内质量控制中发挥重要作用。我们以前证明，缺乏Atg 7的b细胞特异性自噬缺陷小鼠表现出葡萄糖耐量受损，伴随着螯合体1/p62（以下称为p62）的积累。而p62已被报道在调节肝脏和脂肪组织的细胞内稳态中发挥重要作用，我们以前表明，b细胞特异性p62缺乏不会导致任何明显的葡萄糖代谢障碍。在本研究中，我们研究了p62在B细胞自噬缺陷条件下的作用，通过同时灭活Atg 7和p62在B细胞特异性的方式。而p62的积累，大大减少了胰岛的Atg 7和p62双缺陷小鼠，葡萄糖耐量和胰岛素分泌是可比的Atg 7单缺陷小鼠。综上所述，这些发现表明，p62的积累似乎有自噬抑制条件下的b细胞功能的影响不大。
Autophagy is known to play an essential role in intracellular quality control through the degradation of damaged organelles and components. We previously demonstrated that b-cell-specific autophagy deficient mice, which lack Atg7, exhibited impaired glucose tolerance, accompanied by the accumulation of sequestosome 1/p62 (hereafter referred to as p62). Whereas p62 has been reported to play essential roles in regulating cellular homeostasis in the liver and adipose tissue, we previously showed that b-cellspecific p62 deficiency does not cause any apparent impairment in glucose metabolism. In the present study, we investigated the roles of p62 in b cells under autophagy-deficient conditions, by simultaneously inactivating both Atg7 and p62 in a b-cell specific manner. Whereas p62 accumulation was substantially reduced in the islets of Atg7 and p62 double-deficient mice, glucose tolerance and insulin secretion were comparable to Atg7 single-deficient mice. Taken together, these findings suggest that the p62 accumulation appears to have little effect on b-cell function under conditions of autophagy inhibition.