GLUT2 is a high affinity glucosamine transporter

Uldry, Marc; Ibberson, Mark; Hosokawa, Munetaka; Thorens, Bernard

doi:10.1016/s0014-5793(02)03058-2

Cited by 283 publications

(257 citation statements)

References 36 publications

Supporting

Mentioning

245

Contrasting

Unclassified

Order By: Relevance

“…It is possible that GLUT2 transports a solute other than glucose during normal embryogenesis. It was recently recognised that GLUT2 is a high-affinity (low-K m ) transporter of glucosamine [48]. Glucosamine can be a substrate for the intermediates of post-translational glycosylation.…”

Section: Discussionmentioning

confidence: 99%

Expression of the gene encoding the high-K m glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy

Thorens

Loeken

2007

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis Excess glucose transport to embryos during diabetic pregnancy causes congenital malformations. The early postimplantation embryo expresses the gene encoding the high-K m GLUT2 (also known as SLC2A2) glucose transporter. The hypothesis tested here is that high-K m glucose transport by GLUT2 causes malformations resulting from maternal hyperglycaemia during diabetic pregnancy. Materials and methods Glut2 mRNA was assayed by RT-PCR. The K m of embryo glucose transport was determined by measuring 0.5-20 mmol/l 2-deoxy[ 3 H]glucose transport. To test whether the GLUT2 transporter is required for neural tube defects resulting from maternal hyperglycaemia, Glut2 +/− mice were crossed and transient hyperglycaemia was induced by glucose injection on day 7.5 of pregnancy. Embryos were recovered on day 10.5, and the incidence of neural tube defects in wild-type, Glut2 +/− and Glut2 −/− embryos was scored. Results Early postimplantation embryos expressed Glut2, and expression was unaffected by maternal diabetes. Moreover, glucose transport by these embryos showed Michaelis-Menten kinetics of 16.19 mmol/l, consistent with transport mediated by GLUT2. In pregnancies made hyperglycaemic on day 7.5, neural tube defects were significantly increased in wild-type embryos, but Glut2 +/− embryos were partially protected from neural tube defects, and Glut2 −/− embryos were completely protected from these defects. The frequency of occurrence of wild-type, Glut2 +/− and Glut2 −/− embryos suggests that the presence of Glut2 alleles confers a survival advantage in embryos before day 10.5. Conclusions/interpretations High-K m glucose transport by the GLUT2 glucose transporter during organogenesis is responsible for the embryopathic effects of maternal diabetes.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of the gene encoding the high-K m glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy

Thorens

Loeken

2007

Diabetologia

View full text Add to dashboard Cite

show abstract

“…6). This K m is exceptionally high and shows a low affinity for substrate compared with typical sugar transporters such as GLUT1 (Ϸ3 mM glucose), GLUT2 (Ϸ17 mM glucose), and GLUT4 (Ϸ6.6 mM glucose) (27). The V max for TRET1 was considerably higher, indicating that TRET1 is a high-capacity trehalose transporter.…”

Section: Molecular Cloning Of the Tret1mentioning

confidence: 95%

Trehalose transporter 1, a facilitated and high-capacity trehalose transporter, allows exogenous trehalose uptake into cells

Kikawada

Saito

Kanamori

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

227

211

View full text Add to dashboard Cite

Trehalose is potentially a useful cryo-or anhydroprotectant molecule for cells and biomolecules such as proteins and nucleotides. A major obstacle to application is that cellular membranes are impermeable to trehalose. In this study, we isolated and characterized the functions of a facilitated trehalose transporter [trehalose transporter 1 (TRET1)] from an anhydrobiotic insect, Polypedilum vanderplanki. Tret1 cDNA encodes a 504-aa protein with 12 predicted transmembrane structures. Tret1 expression was induced by either desiccation or salinity stress. Expression was predominant in the fat body and occurred concomitantly with the accumulation of trehalose, indicating that TRET1 is involved in transporting trehalose synthesized in the fat body into the hemolymph. Functional expression of TRET1 in Xenopus oocytes showed that transport activity was stereochemically specific for trehalose and independent of extracellular pH (between 4.0 and 9.0) and electrochemical membrane potential. These results indicate that TRET1 is a trehalose-specific facilitated transporter and that the direction of transport is reversible depending on the concentration gradient of trehalose. The extraordinarily high values for apparent K m (>100 mM) and Vmax (>500 pmol/min per oocyte) for trehalose both indicate that TRET1 is a high-capacity transporter of trehalose. Furthermore, TRET1 was found to function in mammalian cells, suggesting that it confers trehalose permeability on cells, including those of vertebrates as well as insects. These characteristic features imply that TRET1 in combination with trehalose has high potential for basic and practical applications in vivo.anhydrobiosis ͉ insect ͉ trehalose transport ͉ Polypedilum vanderplanki dessication-inducible gene

show abstract

“…These have distinct amino acid sequences, substrate specificities, kinetic properties and tissue and cellular localisations [17]. GLUT2 has a uniquely low affinity for glucose (K m ∼17 mmol/l), and can also use mannose, galactose and fructose as low affinity substrates; it has, however, a high affinity for glucosamine (K m ∼0.8 mmol/l) [18]. GLUT2 is present in the basolateral membrane of enterocytes and of epithelial cells from the kidney proximal convoluted tubule where it functions in the second step of transepithelial glucose transport, a process initiated by the apical sodium-glucose cotransporters SGLT1 or SGLT2.…”

Section: Glut2 Structure and Functionmentioning

confidence: 99%

GLUT2, glucose sensing and glucose homeostasis

2014

Self Cite

View full text Add to dashboard Cite

The glucose transporter isoform GLUT2 is expressed in liver, intestine, kidney and pancreatic islet beta cells, as well as in the central nervous system, in neurons, astrocytes and tanycytes. Physiological studies of genetically modified mice have revealed a role for GLUT2 in several regulatory mechanisms. In pancreatic beta cells, GLUT2 is required for glucose-stimulated insulin secretion. In hepatocytes, suppression of GLUT2 expression revealed the existence of an unsuspected glucose output pathway that may depend on a membrane traffic-dependent mechanism. GLUT2 expression is nevertheless required for the physiological control of glucose-sensitive genes, and its inactivation in the liver leads to impaired glucose-stimulated insulin secretion, revealing a liver-beta cell axis, which is likely to be dependent on bile acids controlling beta cell secretion capacity. In the nervous system, GLUT2-dependent glucose sensing controls feeding, thermoregulation and pancreatic islet cell mass and function, as well as sympathetic and parasympathetic activities. Electrophysiological and optogenetic techniques established that Glut2 (also known as Slc2a2)-expressing neurons of the nucleus tractus solitarius can be activated by hypoglycaemia to stimulate glucagon secretion. In humans, inactivating mutations in GLUT2 cause Fanconi-Bickel syndrome, which is characterised by hepatomegaly and kidney disease; defects in insulin secretion are rare in adult patients, but GLUT2 mutations cause transient neonatal diabetes. Genome-wide association studies have reported that GLUT2 variants increase the risks of fasting hyperglycaemia, transition to type 2 diabetes, hypercholesterolaemia and cardiovascular diseases. Individuals with a missense mutation in GLUT2 show preference for sugar-containing foods. We will discuss how studies in mice help interpret the role of GLUT2 in human physiology.

show abstract

GLUT2 is a high affinity glucosamine transporter

Cited by 283 publications

References 36 publications

Expression of the gene encoding the high-K m glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy

Expression of the gene encoding the high-K m glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy

Trehalose transporter 1, a facilitated and high-capacity trehalose transporter, allows exogenous trehalose uptake into cells

GLUT2, glucose sensing and glucose homeostasis

Contact Info

Product

Resources

About