The facilitative glucose transporter GLUT12: what do we know and what would we like to know?

Abstract

Human GLUT12 was isolated from the breast cancer cell line MCF-7 by its homology with GLUT4.Glucose has been described as its main substrate, but it also can transport other sugars. In humans, GLUT12 protein is expressed mainly in insulin sensitive tissues. Functional analysis has showed that GLUT12 transports sugars down its concentration gradient, but it can also work as a proton-coupled symporter. Studies from our laboratory, performed in Xenopus laevis oocytes expressing GLUT12, show that glucose uptake increases in the presence of Na + and induces inward current. These findings suggest a transport mechanism never described for other GLUTs, which would indicate a distinct functional role for GLUT12. In relation with its physiological and pathophysiological function, GLUT12 has been mainly studied due to its role as a secondary insulin-sensitive glucose transporter and its possible implication in impaired insulin signalling pathologies. Its expression in some tumour tissues has been described and recently, it has been proposed as one of the key proteins in the glucose supply to malignant cells. Overall, even though a lot of information about GLUT12 has been released during the last years, its functional characteristics, physiological role or implication in the development of some diseases is still unclear. Therefore, this review of the literature can help to address further investigations needed to elucidate these issues that, in our view, are of great interest mainly due to the direct GLUT12 relation with cancer and probably with diabetes development.

Functional characterization of the human facilitative glucose transporter 12 (GLUT12) by electrophysiological methods

“…We have found in preliminary studies that GLUT12 glucose transport rate is increased in the presence of Na + (29). In MDCK cells over-expressing GLUT12, proton-coupled active glucose transport has been reported (48).…”

“…To compare GLUT12 with the electrogenic SGLT family, which couples glucose and Na + transport, electrophysiological measurements were performed to detect currents that might be associated with sugar transport through GLUT12 (29). Figure 4A The sugar specificity of the currents induced by various sugars was studied.…”

“…It was demonstrated that 2-deoxy-D-glucose (2-DOG) was transported by GLUT12, and that the uptake of [ 3 H]-2-DOG was inhibited by D-glucose>2-DOG> D-galactose>D-fructose>L-glucose (31). Since these are competition studies, except for glucose (27,29), it is not known if the sugars are substrates or inhibitors.…”

“…Initial studies from our laboratory on Xenopus laevis oocytes expressing GLUT12 indicated that glucose transport is enhanced in the presence of external Na + and that glucose induced an inward current (29). In the present work, we set out to characterize the functional properties of GLUT12 using a combination of radiolabeled tracer and electrophysiological methods.…”

Mammalian Sugar Transporters

“…Besides its potential importance for substrate transport in insulin-sensitive tissues, GLUT12 also appears relevant in prostate and breast cancer. However, the physiological role and relevance for GLUT12 remains elusive [37].…”