ASNA-1 positively regulates insulin secretion in C-elegans and mammalian cells
ASNA-1 positively regulates insulin secretion in C-elegans and mammalian cells
复制标题
DOI：
10.1016/j.cell.2006.12.031
复制
发表时间：
2007-02-09
期刊：
影响因子：
64.5
通讯作者：
Naredi, Peter
中科院分区：
文献类型：
--
作者：
Kao, Gautam;Nordenson, Cecilia;Naredi, Peter
C.在没有食物的情况下孵化的蠕虫在第一幼虫期显示生长停滞（U）。虽然已经了解了很多关于后期滞育，dauer，蠕虫进入不利条件下，少得多的是知道的机制，L1逮捕。在这里，我们表明，蠕虫缺乏活动的asna-1基因逮捕增长可逆的L1阶段，即使食物是丰富的。asna-1编码ATP酶，其非自主地发挥调节生长的功能。AsNA-1在有限的感觉神经元和产生胰岛素的肠细胞中表达。AsNA-1突变体的胰岛素分泌减少，而AsNA-1的过表达模拟胰岛素过表达的作用。人ASNA 1在胰腺β细胞中高度表达，但在其他胰腺内分泌细胞类型中不表达，并调节培养细胞中的胰岛素分泌。我们认为ASNA 1是一种进化上保守的胰岛素信号调节剂。
C. elegans worms hatching in the absence of food show growth arrest during the first larval stage (U). While much has been learned about the later diapause, dauer, which worms enter under adverse conditions, much less is known about the mechanisms governing L1 arrest. Here we show that worms lacking activity of the asna-1 gene arrest growth reversibly at the L1 stage even when food is abundant. asna-1 encodes an ATPase that functions nonautonomously to regulate growth. asna-1 is expressed in a restricted set of sensory neurons and in insulin-producing intestinal cells. asna-1 mutants are reduced in insulin secretion while overexpression of asna-1 mimics the effects of insulin overexpression. Human ASNA1 is highly expressed in pancreatic beta cells, but not in other pancreatic endocrine cell types, and regulates insulin secretion in cultured cells. We propose that ASNA1 is an evolutionarily conserved modulator of insulin signaling.