Characterization of human glucose transporter (GLUT) 11 (encoded by SLC2A11), a novel sugar-transport facilitator specifically expressed in heart and skeletal muscle

Abstract

Human GLUT11 (encoded by the solute carrier 2A11 gene, SLC2A11) is a novel sugar transporter which exhibits significant sequence similarity with the members of the GLUT family. The amino acid sequence deduced from its cDNAs predicts 12 putative membrane-spanning helices and all the motifs (sugar-transporter signatures) that have previously been shown to be essential for sugar-transport activity. The closest relative of GLUT11 is the fructose transporter GLUT5 (sharing 41.7% amino acid identity with GLUT11). The human GLUT11 gene (SLC2A11) consists of 12 exons and is located on chromosome 22q11.2. In human tissues, a 7.2kb transcript of GLUT11 was detected exclusively in heart and skeletal muscle. Transfection of COS-7 cells with GLUT11 cDNA significantly increased the glucose-transport activity reconstituted from membrane extracts as well as the specific binding of the sugar-transporter ligand cytochalasin B. In contrast to that of GLUT4, the glucose-transport activity of GLUT11 was markedly inhibited by fructose. It is concluded that GLUT11 is a novel, muscle-specific transport facilitator that is a member of the extended GLUT family of sugar/polyol-transport facilitators.

The SLC2 family of facilitated hexose and polyol transporters

“…When GLUT11 transiently expressed in HEK293 cells is reconstituted in liposomes, glucose transport activity is detected and GLUT11 may have low affinity for this substrate. This activity is inhibited by fructose and GLUT11 exhibits low affinity for cytochalasin B [19]. This property has been verified for the splice variants GLUT11-a and -b.…”

“…The human GLUT11 cDNA was first isolated by PCR on the basis of sequence information obtained from ESTs and from a genomic sequence [19]. Other groups have identified three different, alternative spliced forms of this gene.…”

Regenerating human muscle fibres express GLUT3 protein

“…At present the only conditions under which other glucose transporters are induced in human muscle fibres seem to be regeneration of muscle fibres (expression of GLUT1 and GLUT3). Recently, GLUT8 [10], GLUT11 [11] and GLUT12 [27] has been described for human muscles. Future studies will clarify whether the above picture will have to be modified for these new glucose transporters.…”

GLUT11, but not GLUT8 or GLUT12, is expressed in human skeletal muscle in a fibre type-specific pattern

“…Antisera against GLUT8 [5] and GLUT11 [6] were raised against peptides identical to their C-terminal parts. Affinity-purified GLUT12 polyclonal antibody was generously donated by Susanne Rogers (Melbourne, Australia) [23].…”

“…Thus, GLUT4 seems to be the main glucose transporter in muscle fibres from obese, non-insulin-dependent diabetes mellitus (NIDDM), control and trained subjects and may be responsible for both basal and stimulated glucose transport in human muscle fibres. The mRNA for the novel glucose transporters GLUT8 [5], GLUT11 [6] and GLUT12 [23] has been detected in human skeletal muscle. GLUT12 has drawn particular attention because its mRNA is detected mainly in adipose and muscle tissue, indicating similarities between GLUT12 and GLUT4, and suggesting that GLUT12 may be insulin sensitive.…”