Department of Biology, College of the Holy Cross, Worcester, Massachusetts 01610, USA.
Genetics. 2011 Jun;188(2):369-82. doi: 10.1534/genetics.111.126490. Epub 2011 Mar 24.
In a variety of organisms, including worms, flies, and mammals, glucose homeostasis is maintained by insulin-like signaling in a robust network of opposing and complementary signaling pathways. The hexosamine signaling pathway, terminating in O-linked-N-acetylglucosamine (O-GlcNAc) cycling, is a key sensor of nutrient status and has been genetically linked to the regulation of insulin signaling in Caenorhabditis elegans. Here we demonstrate that O-GlcNAc cycling and insulin signaling are both essential components of the C. elegans response to glucose stress. A number of insulin-dependent processes were found to be sensitive to glucose stress, including fertility, reproductive timing, and dauer formation, yet each of these differed in their threshold of sensitivity to glucose excess. Our findings suggest that O-GlcNAc cycling and insulin signaling are both required for a robust and adaptable response to glucose stress, but these two pathways show complex and interdependent roles in the maintenance of glucose-insulin homeostasis.
在多种生物中，包括蠕虫、苍蝇和哺乳动物，葡萄糖稳态通过胰岛素样信号在一个强大的对立和互补信号通路网络中得以维持。己糖胺信号通路，终止于 O-连接-N-乙酰葡萄糖胺（O-GlcNAc）循环，是营养状态的关键传感器，并已在秀丽隐杆线虫中与胰岛素信号的调节在遗传上相关。在这里，我们证明 O-GlcNAc 循环和胰岛素信号都是秀丽隐杆线虫对葡萄糖应激反应的重要组成部分。发现许多依赖胰岛素的过程对葡萄糖应激敏感，包括生育能力、生殖时机和 dauer 形成，但每种过程对葡萄糖过量的敏感性阈值都不同。我们的研究结果表明，O-GlcNAc 循环和胰岛素信号都是对葡萄糖应激产生强大和适应性反应所必需的，但这两条途径在维持葡萄糖-胰岛素稳态方面表现出复杂和相互依赖的作用。
