Islet primary cilia motility controls insulin secretion

被引:22
|
作者
Cho, Jung Hoon [1 ]
Li, Zipeng A. [1 ]
Zhu, Lifei [1 ]
Muegge, Brian D. [1 ,2 ]
Roseman, Henry F. [1 ,5 ]
Lee, Eun Young [1 ,3 ]
Utterback, Toby [4 ]
Woodhams, Louis G. [4 ]
Bayly, Philip V. [4 ]
Hughes, Jing W. [1 ]
机构
[1] Washington Univ, Dept Med, Sch Med, 660 South Euclid Ave, St Louis, MO USA
[2] VA Med Ctr, Dept Med, 915 North Grand Blvd, St Louis, MO USA
[3] Catholic Univ Korea, Seoul St Marys Hosp, Div Endocrinol & Metab, Dept Internal Med, Seoul, South Korea
[4] Washington Univ, Dept Mech Engn & Mat als Sci, McKelvey Sch Engn, 1 Brookings Dr, St Louis, MO USA
[5] Univ Texas, Med Scientist Training Program, SouthWestern Med Ctr, Dallas, TX USA
来源
SCIENCE ADVANCES | 2022年 / 8卷 / 38期
基金
美国国家卫生研究院;
关键词
HUMAN AIRWAY EPITHELIA; LEFT-RIGHT ASYMMETRY; PANCREATIC-ISLETS; MICE; PROTEIN; RANDOMIZATION; EXPRESSION; DYSKINESIA; MUTATIONS; INSIGHTS;
D O I
10.1126/sciadv.abq8486
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Primary cilia are specialized cell-surface organelles that mediate sensory perception and, in contrast to motile cilia and flagella, are thought to lack motility function. Here, we show that primary cilia in human and mouse pancreatic islets exhibit movement that is required for glucose-dependent insulin secretion. Islet primary cilia contain motor proteins conserved from those found in classic motile cilia, and their three-dimensional motion is dynein-driven and dependent on adenosine 5 '-triphosphate and glucose metabolism. Inhibition of cilia motion blocks beta cell calcium influx and insulin secretion. Human beta cells have enriched ciliary gene expression, and motile cilia genes are altered in type 2 diabetes. Our findings redefine primary cilia as dynamic structures having both sensory and motile function and establish that pancreatic islet cilia movement plays a regulatory role in insulin secretion.
引用
收藏
页数:10
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