FGT-1 is the major glucose transporter in C. elegans and is central to aging pathways

被引:32
作者
Feng, Ying [1 ]
Williams, Barnabas G. [2 ]
Koumanov, Francoise [1 ]
Wolstenholme, Adrian J. [2 ]
Holman, Geoffrey D. [1 ]
机构
[1] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England
[2] Univ Georgia, Dept Infect Dis, Athens, GA 30602 USA
基金
英国医学研究理事会;
关键词
aging; Caenorhabditis elegans; facilitated glucose transporter; isoform 1 (fgt-1); glucose transport; insulin; metabolism; LIFE-SPAN; CAENORHABDITIS-ELEGANS; CALORIC RESTRICTION; GENE; LONGEVITY; INSIGHTS; FAMILY; GLUT1; TRANSLOCATION; METABOLISM;
D O I
10.1042/BJ20131101
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:219 / 229
页数:11
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