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D E James

Publications and source records attributed to D E James.

At least 73 records · Page 4Linked to original sources
PubMed1993

Glucose transport in L6 myoblasts overexpressing GLUT1 and GLUT4.

The roles of the glucose transporter isoforms, GLUT1 and GLUT4, in mediating insulin-stimulated glucose transport were investigated by stably overexpressing the transporters in L6 myoblasts. Levels of GLUT1 and GLUT4 in myoblasts from the cell lines having the highest content of these transporters were approximately 16- and 30-fold higher, respectively, than levels in nontransfected cells. The basal rate of 2-deoxy[3H]glucose uptake was severalfold higher in cells overexpressing GLUT1 than in the parent L6 myoblasts or in control cell lines that were generated by transfecting cells with expression vectors lacking transporter insert. The basal rate was not elevated in any of the lines expressing GLUT4. The net increase in 2-deoxy[3H]glucose uptake produced by insulin was larger in both the GLUT1 and GLUT4 cells than in the control cells. Insulin increased uptake in GLUT4 cells by as much as 6-fold; whereas, the fold increase over basal uptake produced by insulin in GLUT1 cells was comparable to that (2-fold) observed in the control myocytes. Thus, both GLUT1 and GLUT4 can mediate insulin-stimulated glucose transport in L6 myoblasts, although GLUT4 is needed to observe large percentage increases comparable to those observed in skeletal muscle fibers in vivo. In contrast to insulin, the protein phosphatase inhibitors, okadaic acid and calyculin A, inhibited glucose transport in cells expressing either GLUT1 or GLUT4. Calyculin A, which produced a half-maximum effect at 10 nM, was approximately 100 times more potent than okadaic acid in decreasing both basal and insulin-stimulated 2-deoxyglucose uptake. Inhibition of uptake by calyculin A was associated with a decrease in the cell surface concentration of both GLUT1 and GLUT4. These results indicate that increased protein phosphorylation can lead to inhibition of transport mediated by both GLUT1 and GLUT4.

Animals↗
PubMed1993

Glucose transporters and in vivo glucose uptake in skeletal and cardiac muscle: fasting, insulin stimulation and immunoisolation studies of GLUT1 and GLUT4.

Our aim was to study glucose transporters GLUT1 and GLUT4 in relation to in vivo glucose uptake in rat cardiac and skeletal muscle. The levels of both transporters were of a similar order of magnitude in whole muscle tissue (GLUT1/GLUT4 ratio varied from 0.1 to 0.6), suggesting that both may have an important physiological role in regulating muscle glucose metabolism. GLUT4 correlated very strongly (r2 = 0.97) with maximal insulin-stimulated glucose uptake (Rg' max., estimated using the glucose clamp plus 2-deoxy[3H]glucose bolus technique) in six skeletal muscles and heart. A distinct difference in regulation of the two transporters was evident in heart: in 5 h-fasted rats, basal glucose uptake and GLUT1 levels in heart were very high and both were reduced, by 90 and 60% respectively, by 48 h fasting. However, in heart (and in red skeletal muscle), neither GLUT4 levels nor Rg' max. were reduced by 48 h fasting. GLUT1 was shown to be specifically expressed in cardiac myocytes, because intracellular vesicles enriched in GLUT4 contained significant levels of GLUT1. In conclusion, the high association of muscle GLUT4 content with insulin responsiveness in different muscles, and the preservation of both with fasting, supports a predominant role of GLUT4 in insulin-mediated glucose uptake. GLUT1 may play an important role in mediating cardiac muscle glucose uptake in the basal metabolic state. Marked changes in GLUT1 expression with alterations in the metabolic state, such as prolonged fasting, may play an important role in cardiac glucose metabolism.

Animals↗
PubMed1993

GLUT4 phosphorylation and inhibition of glucose transport by dibutyryl cAMP.

To investigate the mechanism responsible for the inhibition of glucose transport by dibutyryl cAMP (Bt2cAMP), two different transporter isoforms (GLUT1 and GLUT4) and several GLUT1/4 chimeric transporters were expressed in Chinese hamster ovary (CHO) cells by using a Sindbis virus expression system. Bt2cAMP inhibited GLUT4-mediated 2-deoxy[3H]glucose (2DOG) uptake by 50% but was without effect on GLUT1-mediated uptake. When the subcellular distribution of GLUT4 was assessed by quantitative immunocytochemistry, neither the overall concentration of GLUT4 nor the regional distribution of GLUT-4 within the plasma membrane was found to be altered by Bt2cAMP. Thus, inhibition of 2DOG uptake by Bt2cAMP appears to be due to a decrease in transporter activity rather than a decrease in the number of transporters exposed at the plasma membrane. By using chimeric transporters, a region of GLUT4 necessary for the inhibitory effect of Bt2cAMP was localized to the last 29 amino acids in the COOH terminus. This intracellular region contains the site (Ser488) phosphorylated in vitro by cAMP-dependent protein kinase (cAdPK). Changing Ser488 to an Ala abolished phosphorylation of GLUT4; however, the inhibitory effect of Bt2cAMP on glucose transport was not diminished by this mutation. Therefore, phosphorylation of GLUT4 was not required for the inhibition. The effects of other nucleotides on GLUT4 transport activity were assessed to investigate the role of cAdPK. Uptake of 2DOG by GLUT4 was inhibited by 8-bromo-AMP, but not by 8-bromo-cAMP, suggesting that the inhibitory effect did not involve activation of cAdPK. Results consistent with this interpretation were obtained with CHO cells (line 10248), which express a cAdPK that is resistant to activation by cAMP. No difference in the concentrations of Bt2cAMP required to inhibit GLUT4-mediated transport was observed in normal CHO cells and 10248 cells. The results presented suggest that the inhibitory effects of Bt2cAMP could be mediated by direct binding of a nucleotide to GLUT4 at a site involving the intracellular COOH terminus of the transporter.

Animals↗
PubMed1993

GLUT-4 NH2 terminus contains a phenylalanine-based targeting motif that regulates intracellular sequestration.

Expression of chimeras, composed of portions of two different glucose transporter isoforms (GLUT-1 and GLUT-4), in CHO cells had indicated that the cytoplasmic NH2 terminus of GLUT-4 contains important targeting information that mediates intracellular sequestration of this isoform (Piper, R. C., C. Tai, J. W. Slot, C. S. Hahn, C. M. Rice, H. Huang, D. E. James. 1992. J. Cell Biol. 117:729-743). In the present studies, the amino acid constituents of the GLUT-4 NH2-terminal targeting domain have been identified. GLUT-4 constructs containing NH2-terminal deletions or alanine substitutions within the NH2 terminus were expressed in CHO cells using a Sindbis virus expression system. Deletion of eight amino acids from the GLUT-4 NH2 terminus or substituting alanine for phenylalanine at position 5 in GLUT-4 resulted in a marked accumulation of the transporter at the plasma membrane. Mutations at other amino acids surrounding Phe5 also caused increased cell surface expression of GLUT-4 but not to the same extent as the Phe5 mutation. GLUT-4 was also localized to clathrin lattices and this colocalization was abolished when either the first 13 amino acids were deleted or when Phe5 was changed to alanine. To ascertain whether the targeting information within the GLUT-4 NH2-terminal targeting domain could function independently of the glucose transporter structure this domain was inserted into the cytoplasmic tail of the H1 subunit of the asialoglycoprotein receptor. H1 with the GLUT-4 NH2 terminus was predominantly localized to an intracellular compartment similar to GLUT-4 and was sequestered more from the cell surface than was the wild-type H1 protein. It is concluded that the NH2 terminus of GLUT-4 contains a phenylalanine-based targeting motif that mediates intracellular sequestration at least in part by facilitating interaction of the transporter with endocytic machinery located at the cell surface.

Amino Acid Sequence↗
PubMed1993

Jejunal/kidney glucose transporter isoform (Glut-5) is expressed in the human blood-brain barrier.

The recently cloned Glut-5, glucose transporter isoform, is expressed in human jejunum and kidney. Employing previously characterized polyclonal antibodies directed towards the C-terminus region of the derived human Glut-5 peptide and Western blot analysis, a 50-55 kilodalton Glut-5 protein was detected in adult human brain homogenates. The amount of Glut-5 protein in brain was 4-fold lower when compared to the levels in adult kidney. Immunohistochemical analysis using cerebral and cerebellar sections demonstrated Glut-5 immunoreactivity in only some of the Glut-1 and factor VIII-positive brain microvascular endothelial cells, the intravascular red and white blood cells being negative. This selective localization pattern was confirmed by the 5-fold enrichment of Glut-5 vs. a 20-fold enrichment of Glut-1 in an isolated human cerebral cortical microvascular preparation, when compared to whole cerebral homogenates. We conclude that Glut-5 is localized in the endothelial cells of human brain microvasculature. Unlike other fructose using tissues, where Glut-5 may subserve the role of a fructose carrier, in brain where fructose is not used as a substrate, Glut-5 may transport glucose alone. This role of Glut-5 in conjunction with the previously characterized brain endothelial Glut-1 and Glut-3 needs further elucidation.

Blood-Brain Barrier↗
PubMed1992

Polarized distribution of glucose transporter isoforms in Caco-2 cells.

We have examined the expression and cellular location of facilitated glucose transporter proteins (GLUT1, -3, and -5) in a human colonic epithelial cell line (Caco-2) by using peptide-specific antibodies. A differential cellular distribution of these transporters was observed in differentiated (greater than 14 days postconfluence) Caco-2 cells by immunofluorescence and immunoelectron microscopy. GLUT1 was localized primarily to the basolateral membrane, whereas GLUT3 was predominantly localized to the apical membrane. GLUT5, which was detected in only approximately 40% of fully differentiated Caco-2 cells, was found primarily in the apical membrane but was also present in both basolateral and intracellular membranes. A Na(+)-independent glucose transport system in the apical membrane of Caco-2 cells has been described previously [Blais, A., Bissonnette, A. & Berteloot, A. (1987) J. Membr. Biol. 99, 113-125], and we propose that GLUT3 mediates this process. The amino acid sequence identity (57%) and structural conservation between GLUT1 and GLUT3 may make these transporters an ideal model system for examining the molecular basis for polarized sorting of membrane proteins.

Adenocarcinoma↗
PubMed1992

GLUT4 facilitates insulin stimulation and cAMP-mediated inhibition of glucose transport.

The glucose transporter isoform GLUT4 is found only in cells that exhibit insulin-sensitive glucose transport. To investigate the function of this transporter, L6 myoblasts were stably transfected with GLUT4 cDNA. GLUT4 underwent insulin-dependent movement to the cell surface in myoblasts overexpressing the transporter. One cell line (243-6) expressed sufficient levels of the GLUT4 protein to study insulin-dependent glucose transport. Unlike wild-type L6 cells, 243-6 myoblasts exhibited two features that are characteristic of differentiated muscle fibers and adipocytes in vivo: a large insulin-stimulated component of glucose transport and inhibition of this stimulated component by cAMP. Relative to normal L6 cells, 243-6 cells responded to insulin or insulin-like growth factor 1 with a 5-fold larger increase in 2-deoxy[3H]glucose uptake. N6,O2'-Dibutyryladenosine 3',5'-cyclic monophosphate (Bt2cAMP) did not inhibit transport in normal L6 myoblasts, which express only GLUT1, but inhibited IGF-1/insulin-stimulated transport by 50% in 243-6 cells. The effect of cAMP was investigated further by using Chinese hamster ovary cells transiently expressing GLUT1 and GLUT4. Bt2cAMP inhibited glucose transport only in Chinese hamster ovary cells expressing GLUT4. These results indicate that cAMP-mediated inhibition of glucose transport is dependent on expression of the GLUT4 isozyme.

Animals↗
PubMed1992

Immunocytochemical and biochemical studies of GLUT4 in rat skeletal muscle.

In muscle and adipocytes, glucose transport is regulated by the translocation of insulin regulatable glucose transporters (GLUT4) between an intracellular compartment and the cell surface. In these studies we have characterized the cellular compartments containing GLUT4 in rat skeletal muscle. Immunocytochemical studies showed that in unstimulated muscle, GLUT4 was not present in surface membranes. Tubulo-vesicular structures clustered in the trans Golgi reticulum were enriched in GLUT4. GLUT4 underwent translocation to the sarcolemma in response to combined stimulation with insulin and exercise. Using immunoisolation, the intracellular GLUT4 vesicles (IRGTV) were purified 300-fold over the cell homogenate. IRGTV from unstimulated muscle were not enriched in markers specific for the sarcolemma, transverse tubules, sarcoplasmic reticulum or mitochondria; this was confirmed using gel filtration chromatography. Insulin resulted in a 40% decrease in GLUT4 levels in IRGTV confirming that this represents the intracellular compartment of GLUT4. GLUT4 is a major component of the IRGTV, constituting at least 5% of total vesicle protein. A subset of polypeptides are also markedly enriched in the muscle IRGTV. In conclusion, these data suggest that translocation of GLUT4 from intracellular tubulo-vesicular structures is the major mechanism by which insulin and exercise regulate muscle glucose transport.

Animals↗
PubMed1992

Cellular and molecular biology of the beta cell.

Considerable progress has been made in our understanding of islet-cell function and its relationship to regulation of whole body glucose metabolism. At the genetic level, the regulatory regions in islet-specific genes are being characterised. Transcription factors that interact with these regions have been cloned and these will be instructive in elucidating how islet-specific genes are regulated during development and regeneration. Identification of the enzymes responsible for proteolytic conversion of proinsulin to insulin represents a major advance in understanding prohormone processing. Cleavage of proinsulin is mediated by at least two prohormone convertases (PC3/PC1 and PC2). Their activity is regulated by an acidic gradient between the Golgi and secretory granules and by calcium ions. It is not yet clear how insulin or the PC's are specifically diverted into the regulated secretory pathway. Regulation at this step may be defective in some diabetic patients resulting in relatively elevated circulating proinsulin levels. Specific features of GLUT 2 and glucokinase (GK), proteins that regulate Beta-cell glucose transport and phosphorylation, indicate that these may be key components of the glucose sensor. GLUT 2 is necessary to reconstitute glucose-sensitive insulin secretion in pituitary tumour cells expressing a proinsulin cDNA. Furthermore, the expression of GLUT 2 in Beta cells, but not in hepatocytes, is decreased in diabetes mellitus. However, under normal circumstances GK is probably rate limiting for Beta-cell glucose utilisation. Thus, it is likely that both GLUT 2 and GK determine the set point for glucose-stimulated insulin secretion. Elucidation of distal effectors that regulate insulin secretion is also crucial to our understanding of Beta-cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1992

The efficient intracellular sequestration of the insulin-regulatable glucose transporter (GLUT-4) is conferred by the NH2 terminus.

GLUT-4 is the major facilitative glucose transporter isoform in tissues that exhibit insulin-stimulated glucose transport. Insulin regulates glucose transport by the rapid translocation of GLUT-4 from an intracellular compartment to the plasma membrane. A critical feature of this process is the efficient exclusion of GLUT-4 from the plasma membrane in the absence of insulin. To identify the amino acid domains of GLUT-4 which confer intracellular sequestration, we analyzed the subcellular distribution of chimeric glucose transporters comprised of GLUT-4 and a homologous isoform, GLUT-1, which is found predominantly at the cell surface. These chimeric transporters were transiently expressed in CHO cells using a double subgenomic recombinant Sindbis virus vector. We have found that wild-type GLUT-4 is targeted to an intracellular compartment in CHO cells which is morphologically similar to that observed in adipocytes and muscle cells. Sindbis virus-produced GLUT-1 was predominantly expressed at the cell surface. Substitution of the GLUT-4 amino-terminal region with that of GLUT-1 abolished the efficient intracellular sequestration of GLUT-4. Conversely, substitution of the NH2 terminus of GLUT-1 with that of GLUT-4 resulted in marked intracellular sequestration of GLUT-1. These data indicate that the NH2-terminus of GLUT-4 is both necessary and sufficient for intracellular sequestration.

Amino Acid Sequence↗
PubMed1992

Translocation of the glucose transporter (GLUT4) to the cell surface in permeabilized 3T3-L1 adipocytes: effects of ATP insulin, and GTP gamma S and localization of GLUT4 to clathrin lattices.

Insulin stimulates the movement of two glucose transporter isoforms (GLUT1 and GLUT4) to the plasma membrane (PM) in adipocytes. To study this process we have prepared highly purified PM fragments by gently sonicating 3T3-L1 adipocytes grown on glass coverslips. Using confocal laser immunofluorescence microscopy we observed increased PM labeling for GLUT1 (2.3-fold) and GLUT4 (eightfold) after insulin treatment in intact cells. EM immunolabeling of PM fragments indicated that in the nonstimulated state GLUT4 was mainly localized to flat clathrin lattices. Whereas GLUT4 labeling of clathrin lattices was only slightly increased after insulin treatment, labeling of uncoated PM regions was markedly increased with insulin. These data suggest that GLUT4 recycles from the cell surface both in the presence and absence of insulin. In streptolysin-O permeabilized adipocytes, insulin, and GTP gamma S increased PM levels of GLUT4 to a similar extent as observed with insulin in intact cells. In the absence of an exogenous ATP source the magnitude of these effects was considerably reduced. Removal of ATP per se caused a significant increase in cell surface levels of GLUT4 suggesting that ATP may be required for intracellular sequestration of these transporters. When insulin and GTP gamma S were added together, in the presence of ATP, PM GLUT4 levels were similar to levels observed when either insulin or GTP gamma S was added individually. Addition of GTP gamma S was able to overcome this ATP dependence of insulin-stimulated GLUT4 movement. GTP gamma S had no effect on constitutive secretion of adipsin in permeabilized cells. In addition, there was no effect of insulin or GTP gamma S on GLUT4 movement to the PM in noninsulin sensitive streptolysin-O-permeabilized 3T3-L1 fibroblasts overexpressing GLUT4. We conclude that the insulin-stimulated movement of GLUT4 to the cell surface in adipocytes may require ATP early in the insulin signaling pathway and a GTP-binding protein(s) at a later step(s). We propose that the association of GLUT4 with clathrin lattices may be important in maintaining the exclusive intracellular location of this transporter in the absence of insulin.

3T3 Cells↗
PubMed1992

Exercise training, glucose transporters, and glucose transport in rat skeletal muscles.

It was previously found that voluntary wheel running induces an increase in the insulin-sensitive glucose transporter, i.e., the GLUT4 isoform, in rat plantaris muscle (K. J. Rodnick, J. O. Holloszy, C. E. Mondon, and D. E. James. Diabetes 39: 1425-1429, 1990). The present study was undertaken to determine whether 1) the increase in muscle GLUT4 protein is associated with an increase in maximally stimulated glucose transport activity, 2) a conversion of type IIb to type IIa or type I muscle fibers plays a role in the increase in GLUT4 protein, and 3) an increase in the GLUT1 isoform is a component of the adaptation of muscle to endurance exercise. Five weeks of voluntary wheel running that resulted in a 33% increase in citrate synthase activity induced a 50% increase in GLUT4 protein in epitrochlearis muscles of female Sprague-Dawley rats. The rate of 2-deoxy-glucose transport maximally stimulated with insulin or insulin plus contractions was increased approximately 40% (P less than 0.05). There was no change in muscle fiber type composition, evaluated by myosin ATPase staining, in the epitrochlearis. There was also no change in GLUT1 protein concentration. We conclude that an increase in GLUT4, but not of GLUT1 protein, is a component of the adaptive response of muscle to endurance exercise and that the increase in GLUT4 protein is associated with an increased capacity for glucose transport.

Adaptation, Physiological↗
PubMed1992

Developmental expression of insulin-regulatable glucose transporter GLUT-4.

The insulin-regulatable glucose transporter (GLUT-4) is expressed in adipose tissue and in cardiac and skeletal muscle (D. E. James, R. Brown, J. Navarro, and P. F. Pilch. Nature Lond. 333: 183-185, 1988). We examined GLUT-4 development between postnatal days 1 and 41 (P1-P41) in male and female rats in these tissues by quantitative immunoblotting. GLUT-4 was detectable in each tissue at comparable levels at P1. However, the subsequent patterns of GLUT-4 development were distinctive. GLUT-4 increased in the diaphragm after P7, peaked at P20, and then declined. GLUT-4 expression in the heart increased rapidly after P7 to plateau on P41 at levels four times greater than the diaphragm. In sharp contrast, adipose tissue expression was highest between P3 and P5 but declined to a nadir at P20 before rebounding at P34. These patterns were observed for both sexes within each tissue, but female GLUT-4 expression was higher in diaphragm and heart and lower in adipose tissue. The expression of GLUT-4 appears to be regulated in a tissue-specific manner by a developmental program that may coordinate the expression of other proteins of metabolic importance.

Adipose Tissue↗
PubMed1992

Insulin-regulated sorting of glucose transporters in 3T3-L1 adipocytes.

Two glucose transporters (GLUT-4 and GLUT-1) move from within the cell to the plasma membrane (PM) when 3T3-L1 adipocytes are stimulated with insulin. To study the sorting of these two molecules, vesicles containing GLUT-4 and GLUT-1 were immunoadsorbed from basal and insulin-treated cells. Two different vesicle populations were isolated as follows: 1) a compartment that contained the majority of intracellular GLUT-4 and GLUT-1 and 2) a subpopulation of vesicles containing 43% of the intracellular GLUT-4 that was highly insulin regulatable and that contained relatively low levels of GLUT-1. After incubation at 19 degrees C, basal glucose transport was slightly increased, whereas insulin-dependent transport was blocked. Consistent with these observations, cell surface GLUT-1 levels were increased in the basal state, whereas insulin-dependent translocation of GLUT-4 to the PM was blocked at 19 degrees C. However, insulin-dependent sorting of GLUT-4 within the intracellular compartment was still evident at 19 degrees C. These data indicate that GLUT-1 and GLUT-4 are heterogeneously distributed throughout the same intracellular compartment in 3T3-L1 adipocytes. Furthermore, we have uncoupled two distinct steps in the insulin-dependent movement of GLUT-4 to the cell surface. These include movement of GLUT-4 out of its storage compartment and accumulation of GLUT-4 at the cell surface. Only the former step occurs in cells preincubated at 19 degrees C.

3T3 Cells↗
PubMed1992

Feedback inhibition of insulin gene expression by insulin.

To examine the possible involvement of insulin and glucose in regulation of pancreatic islet gene expression, hyperinsulinemic (insulin infusion 4.1 mU/kg per min) clamps were performed for 12 h in rats at two different levels of glycemia (either 3 or 8 mM). A control group received a saline infusion for 12 h. At the end of the 12-h study period, pancreatic RNA was extracted, proinsulin and amylin mRNAs were measured on total RNA, and glucokinase and glucose transporter (GLUT-2) mRNAs were measured on poly(A)+ RNA by dot blot analysis. In insulin-infused hypoglycemic rats, there was a 58% decrement in proinsulin mRNA (P less than 0.01) relative to levels in controls, with no change in amylin, glucokinase, or islet GLUT-2 mRNAs. In insulin-infused hyperglycemic rats, there was a comparable decrement (44%, P less than 0.01) in proinsulin mRNA and a smaller decrement in GLUT-2 mRNA (32%, P less than 0.05), with no change in amylin or glucokinase mRNAs relative to levels in control animals. These studies suggest that insulin has a negative feedback inhibitory effect on its own synthesis. The mechanism of inhibition is unknown. It could be a direct effect of insulin on its own transcription, or alternatively an indirect effect mediated by humoral or neural factors. Sustained hyperinsulinemia may lead to suppression of normal islet beta cells and may contribute to the ultimate hypoinsulinemia of noninsulin-dependent diabetes mellitus.

Amyloid↗
PubMed1992

Cellular localization and characterization of Glut 3 glucose transporter isoform in human brain.

In the present study we examined the expression and localization of Glut 3 in human brain using peptide-specific antisera. Glut 3 was expressed at 2-3 times higher levels in cerebral cortex from adult (n = 6) compared to that from neonatal infants (n = 4; P less than 0.05). However, similar levels of immunoreactive Glut 3 were present in cerebellum from adults (n = 6) and newborns (n = 4). Cellular localization of Glut 3 in adult (n = 5) and neonatal (n = 5) infant brains was undertaken by immunohistochemical analysis. Glut 3 was visible in the adult neuropil of the cerebral cortex; in certain cellular processes within the deeper cortical layers; in intravascular white cells, including monocytes, lymphocytes and granulocytes; and in microvascular endothelial cells. Neither the premature nor the mature newborn cerebral cortex exhibited Glut 3 labeling in the neuropil or microvasculature. In the cerebellum, given the stratified nature of the cellular arrangement, Glut 3 was more clearly and definitively noted in the cellular processes at all stages of development. Double labeling studies using neuronal (neurofilament) and astrocytic (glial fibrillary acidic protein) markers indicated that Glut 3 was primarily expressed in neurons. We conclude that Glut 3 is localized in many cellular components, including white blood cells in human brain. The prominent localization of Glut 3 to mature neuronal processes suggests an essential role for this transporter in regulating fuel requirements for dendritic and axonal traffic, thereby mediating neurotransmission. Further study is required to address the possibility that another as yet undefined glucose transporter isoform is expressed in other cell-specific regions of the brain.

Adult↗