*Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, U.K.
Biochem J. 2013 Dec 1;456(2):219-29. doi: 10.1042/BJ20131101.
Caenorhabditis elegans is widely used as a model for investigation of the relationships between aging, nutrient restriction and signalling via the DAF-2 (abnormal dauer formation 2) receptor for insulin-like peptides and AGE-1 [ageing alteration 1; orthologue of PI3K (phosphoinositide 3-kinase)], but the identity of the glucose transporters that may link these processes is unknown. We unexpectedly find that of the eight putative GLUT (glucose transporter)-like genes only the two splice variants of one gene have a glucose transport function in an oocyte expression system. We have named this gene fgt-1 (facilitated glucose transporter, isoform 1). We show that knockdown of fgt-1 RNA leads to loss of glucose transport and reduced glucose metabolism in wild-type worms. The FGT-1 glucose transporters of C. elegans thus play a key role in glucose energy supply to C. elegans. Importantly, knockdown of fgt-1 leads to an extension of lifespan equivalent, but not additive, to that observed in daf-2 and age-1 mutant worms. The results of the present study are consistent with DAF-2 and AGE-1 signalling stimulating glucose transport in C. elegans and this process being associated with the longevity phenotype in daf-2 and age-1 mutant worms. We propose that fgt-1 constitutes a common axis for the lifespan extending effects of nutrient restriction and reduced insulin-like peptide signalling.
秀丽隐杆线虫被广泛用作研究衰老、营养限制以及胰岛素样肽 DAF-2(异常持久形成 2)受体和 AGE-1(衰老改变 1;PI3K 的同源物)信号之间关系的模型,但将这些过程联系起来的葡萄糖转运体的身份尚不清楚。我们出人意料地发现,在 8 个假定的 GLUT(葡萄糖转运体)样基因中,只有一个基因的两个剪接变体在卵母细胞表达系统中具有葡萄糖转运功能。我们将这个基因命名为 fgt-1(促进葡萄糖转运体,异构体 1)。我们表明,fgt-1 RNA 的敲低导致野生型蠕虫中葡萄糖转运和葡萄糖代谢的丧失。秀丽隐杆线虫的 FGT-1 葡萄糖转运体因此在向秀丽隐杆线虫提供葡萄糖能量方面发挥着关键作用。重要的是,fgt-1 的敲低导致寿命延长等效,但不是 daf-2 和 age-1 突变体蠕虫中观察到的寿命延长的附加效果。本研究的结果与 DAF-2 和 AGE-1 信号刺激秀丽隐杆线虫中的葡萄糖转运一致,并且这个过程与 daf-2 和 age-1 突变体蠕虫中的长寿表型相关。我们提出 fgt-1 构成了营养限制和降低胰岛素样肽信号延长寿命的共同轴。