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At least 235 records · Page 13Linked to original sources
PubMed1996

Exercise induces the translocation of GLUT4 to transverse tubules from an intracellular pool in rat skeletal muscle.

Exercise stimulates glucose transport in skeletal muscle by increasing the number of GLUT4 glucose transporters at the cell surface. The effect of exercise on GLUT4 content in transverse tubules, which are deep extensions of the plasma membrane involved in myofiber contraction, has never been studied. In the present study, we have investigated whether acute exercise induces translocation of GLUT4 to the transverse tubules. Plasma membranes and transverse tubules were isolated from control and exercised rats by a newly developed membrane fractionation procedure. As expected, acute exercise increased GLUT4 content in plasma membranes (95%; p < 0.01). Importantly, exercise also significantly increased GLUT4 content in a transverse tubule-enriched fraction (60%; p < 0.05). Furthermore, acute exercise was found to decrease GLUT4 content in an intracellular membrane fraction (-40%; p < 0.001). In conclusion, this study demonstrates that GLUT4 is translocated not only to the plasma membranes but also to the transverse tubules in acutely exercised muscles. The results also indicate that GLUT4 is recruited from a novel intracellular membrane fraction.

5'-Nucleotidase↗
PubMed1996

Effects of overexpressing wild-type and mutant PDGF receptors on translocation of GLUT4 in transfected rat adipose cells.

Activation of phosphatidylinositol 3-kinase (PI3K) by insulin is necessary for the effect of insulin to recruit GLUT4 to the cell surface in insulin target cells. In adipose cells, stimulation of endogenous PDGF receptors (PDGF-R) results in increased PI3K activity without causing recruitment of GLUT4. We overexpressed wild-type or mutant forms of the PDGF-R in rat adipose cells and examined their effects on PDGF- and insulin-stimulated recruitment of co-transfected epitope-tagged GLUT4. Control cells expressing only tagged GLUT4 had a 3-fold increase in cell surface GLUT4 upon insulin stimulation but no response to PDGF. Cells overexpressing wild-type PDGF-R maintained insulin responsiveness and, in addition, acquired the ability to recruit GLUT4 in response to PDGF. Surprisingly, overexpression of F740/ F751 (mutant PDGF-R unable to directly activate PI3K) led to similar results. Nevertheless, wortmannin (an inhibitor of PI3K) blocked effects of both PDGF and insulin to recruit GLUT4. Our data suggest that overexpression of PDGF-R mediates positive effects on GLUT4 translocation by a wortmannin sensitive pathway not dependent on direct interaction of the PDGF-R with PI3K.

Adipose Tissue↗
PubMed2001

Subcellular compartmentalization and trafficking of the insulin-responsive glucose transporter, GLUT4.

Insulin increases glucose transport into cells of target tissues, primarily striated muscle and adipose. This is accomplished via the insulin-dependent translocation of the facilitative glucose transporter 4 (GLUT4) from intracellular storage sites to the plasma membrane. Insulin binds to the cell-surface insulin receptor and activates its intrinsic tyrosine kinase activity. The subsequent activation of phosphatidylinositol 3-kinase (PI 3-K) is well known to be necessary for the recruitment of GLUT4 to the cell surface. Both protein kinase B (PKB) and the atypical protein kinase C(lambda/zeta) (PKClambda/zeta) appear to function downstream of PI 3-K, but how these effectors influence GLUT4 translocation remains unknown. In addition, emerging evidence suggests that a second signaling cascade that functions independently of the PI 3-K pathway is also required for the insulin-dependent translocation of GLUT4. This second pathway involves the Rho-family GTP binding protein TC10, which functions within the specialized environment of lipid raft microdomains at the plasma membrane. Future work is necessary to identify the downstream effectors that link TC10, PKB, and PKClambda/zeta to GLUT4 translocation. Progress in this area will come from a better understanding of the compartmentalization of GLUT4 within the cell and of the mechanisms responsible for targeting the transporter to specialized insulin-responsive storage compartments. Furthermore, an understanding of how GLUT4 is retained within and released from these compartments will facilitate the identification of downstream signaling molecules that function proximal to the GLUT4 storage sites.

Adipocytes↗
PubMed1994

Isoproterenol inhibits cyclic AMP-mediated but not insulin-mediated translocation of the GLUT4 glucose transporter isoform.

Isoproterenol is a beta adrenergic agonist whose effects have been attributed to the generation of cAMP. Previous studies have shown that it inhibits glucose transport in adipocytes without changing the number of insulin-responsive glucose transporters (GLUT4) on the cell surface. However, we have shown previously that cAMP stimulates translocation of GLUT4 to the cell surface in adipocytes (Kelada et al. J Biol Chem 267, 7021-7025, 1992). We therefore further investigated the mechanisms involved in isoproterenol regulation of glucose transport. Consistent with the effects of dibutyryl cAMP, we found that a low concentration of isoproterenol (10 nM) stimulated glucose transport and the translocation of GLUT4 from the low density microsomal fraction to the plasma membrane. By contrast, a higher concentration of isoproterenol (1 microM) did not stimulate transport or GLUT4 translocation and furthermore inhibited dibutyryl cAMP-stimulated GLUT4 translocation. This inhibitory effect was specific for cAMP since isoproterenol had no effect on insulin-stimulated GLUT4 translocation. We conclude that isoproterenol has a biphasic effect on glucose transport, mediated by acute translocation of GLUT4 at low concentrations and by inhibition of intrinsic activity at high concentration, both of which may be explained by effects of cAMP. It has a further cAMP-independent effect at high concentration to inhibit cAMP-mediated translocation of GLUT4.

Adipocytes↗
PubMed1997

Regional variation in adipose tissue insulin action and GLUT4 glucose transporter expression in severely obese premenopausal women.

Insulin action and GLUT4 expression were examined in adipose tissue of severely obese premenopausal women undergoing gastrointestinal surgery. Fat samples were taken from three different anatomical regions: the subcutaneous abdominal site, the round ligament (deep abdominal properitoneal fat), and the greater omentum (deep abdominal intraperitoneal fat). The stimulatory effect of insulin on glucose transport and the ability of the hormone to inhibit lipolysis were determined in adipocytes isolated from these three adipose depots. Insulin stimulated glucose transport 2-3 times over basal rates in all adipocytes. However, round ligament adipose cells showed a significantly greater responsiveness to insulin when compared to subcutaneous and omental adipocytes. Round ligament fat cells also displayed the greatest sensitivity and maximal antilipolytic response to insulin. We also investigated whether regional differences in fat cell insulin-stimulated glucose transport were linked to a differential expression of the GLUT4 glucose transporter. GLUT4 protein content in total membranes was 5 and 2.2 times greater in round ligament adipose tissue than in subcutaneous and omental fat depots, respectively. Moreover, GLUT4 mRNA levels were 2.1 and 3 times higher in round ligament than in subcutaneous or omental adipose tissues, respectively. Adipose tissue GLUT4 protein content was strongly and negatively associated (r = -0.79 to -0.89, p < 0.01) with the waist-to-hip ratio but not with total adiposity. In conclusion, these results demonstrate the existence of site differences in adipose tissue insulin action in morbidly obese women. The greater insulin effect on glucose transport in round ligament adipocytes was associated with a higher expression of GLUT4 when compared to subcutaneous abdominal and omental fat cells. Moreover, despite the regional variation in GLUT4 expression, an increased proportion of abdominal fat was found to be associated with lower levels of GLUT4 in all adipose regions investigated.

Adipocytes↗
PubMed2002

Gene gun bombardment-mediated expression and translocation of EGFP-tagged GLUT4 in skeletal muscle fibres in vivo.

Cellular protein trafficking has been studied to date only in vitro or with techniques that are invasive and have a low time resolution. To establish a gentle method for analysis of glucose transporter-4 (GLUT4) trafficking in vivo in fully differentiated rat skeletal muscle fibres we combined the enhanced green fluorescent protein (EGFP) labelling technique with physical transfection methods in vivo: intramuscular plasmid injection or gene gun bombardment. During optimisation experiments with plasmid coding for the EGFP reporter alone EGFP-positive muscle fibres were counted after collagenase treatment of in vivo transfected flexor digitorum brevis (FDB) muscles. In contrast to gene gun bombardment, intramuscular injection produced EGFP expression in only a few fibres. Regardless of the transfection technique, EGFP expression was higher in muscles from 2-week-old rats than in those from 6-week-old rats and peaked around 1 week after transfection. The gene gun was used subsequently with a plasmid coding for EGFP linked to the C-terminus of GLUT4 (GLUT4-EGFP). Rats were anaesthetised 5 days after transfection and insulin given i.v. with or without accompanying electrical hindleg muscle stimulation. After stimulation, the hindlegs were fixed by perfusion. GLUT4-EGFP-positive FDB fibres were isolated and analysed by confocal microscopy. The intracellular distribution of GLUT4-EGFP under basal conditions as well as after translocation to the plasma membrane in response to insulin, contractions, or both, was in accordance with previous studies of endogenous GLUT4. Finally, GLUT4-EGFP trafficking in quadriceps muscle in vivo was studied using time-lapse microscopy analysis in anaesthetised mice and the first detailed time-lapse recordings of GLUT4-EGFP translocation in fully differentiated skeletal muscle in vivo were obtained.

Animals↗
PubMed1996

Effect of vanadate on glucose transporter (GLUT4) intrinsic activity in skeletal muscle plasma membrane giant vesicles.

Maximally effective concentrations of vanadate (a phosphotyrosine phosphatase inhibitor) increase glucose transport in muscle less than maximal insulin stimulation. This might be due to vanadate-induced decreased intrinsic activity of GLUT4 accompanying GLUT4 translocation. Thus, the effect of vanadate (NaVO3) on glucose transporter (GLUT4) intrinsic activity (V(max) = intrinsic activity x [GLUT4 protein]) was studied in muscle plasma membrane giant vesicles. Giant vesicles (average diameter 7.6 microns) were produced by collagenase treatment of rat skeletal muscle. The vesicles were incubated for 1.5 h with concentrations of vanadate ranging from 3 to 40 mmol l-1 at 34 degrees C before being used for determination of glucose transport. The dose-response curve showed that vanadate decreased the specific D-glucose uptake by a maximum of 70% compared with a control preparation. The vanadate-induced decrease in glucose uptake was not due to a decrease in number of vesicles. To further verify the apparent vanadate-induced decrease in GLUT4 intrinsic activity, the kinetics of glucose transport were also examined. In the presence of 10 mmol l-1 vanadate the V(max) and K(m) were decreased (P < 0.05, n = 6) 55% and 60%, respectively, compared with control. The plasma membrane GLUT4 protein content was not changed in response to vanadate. It is concluded that vanadate decreased glucose transport per GLUT4 (intrinsic activity). This finding suggests that regulation of glucose transport in skeletal muscle can involve changes in GLUT4 intrinsic activity.

Animals↗
PubMed1996

Dynamics of insulin-stimulated translocation of GLUT4 in single living cells visualised using green fluorescent protein.

Insulin increases glucose uptake by promoting the translocation of the GLUT4 isoform of glucose transporters to the plasma membrane. We have studied this process in living single cells by fusing green fluorescent protein (GFP) to the N-terminus (GFP-GLUT4) or C-terminus (GLUT4-GFP), of GLUT4. Both chimeras were expressed in a perinuclear compartment of CHO cells, and in a vesicular distribution through the cytosol. Insulin promoted an increase in plasma membrane fluorescence as a result of net translocation of the chimeras to the cell surface. GLUT4-GFP, but not GFP-GLUT4, was re-internalised upon the removal of insulin suggesting that a critical internalisation signal sequence exists in the N-terminus of GLUT4. The use of GFP thus allows an analysis of GLUT4 trafficking in single living cells.

Animals↗
PubMed1996

Analyses of the co-localization of cellubrevin and the GLUT4 glucose transporter in rat and human insulin-responsive tissues.

We have investigated the subcellular distribution and association of cellubrevin, a low molecular weight protein implicated in the process of membrane fusion, with intracellular membranes containing the insulin-sensitive GLUT4 glucose transporter from rat adipocytes, rat skeletal muscle and human skeletal muscle. SDS-PAGE and immunoblot analyses of subcellular fractions of adipocytes and skeletal muscle indicated a positive correlation between the distribution of GLUT4 and cellubrevin in intracellular membrane fractions tested from all tissues. The identity of the polypeptide reacting with antiserum against cellubrevin was further confirmed on the basis of its susceptibility to proteolysis by tetanus toxin. Immunoisolation of GLUT4-containing vesicles from a microsomal fraction enriched with GLUT4 and cellubrevin revealed that cellubrevin could be coprecipitated with GLUT4 vesicles from adipocytes. In contrast, intracellular GLUT4 vesicles isolated from both rat and human skeletal muscle were devoid of any detectable immunoreactivity towards cellubrevin. The observation that cellubrevin does not colocalise with intracellular GLUT4 in skeletal muscle from two different species, rat and human, would strongly suggest that it is unlikely to participate in the insulin-induced delivery of GLUT4 to the cell surface in skeletal muscle.

Adipocytes↗
PubMed1993

Effects of wheel running on glucose transporter (GLUT4) concentration in skeletal muscle of young adult and old rats.

We examined the effects of voluntary exercise on glucose transporter concentration in skeletal muscle from young adult and old female Long-Evans rats. Rats had free access to voluntary running wheels beginning at 4 months of age or remained sedentary. Exercising rats ran approximately 7.5, 6.2, 5.6 and 5.3 km/day during their 6th, 8th, 9th and 10th month of age, respectively. During the 23rd, 24th and 25th month of age running distance averaged 3.0, 2.8 and 2.4 km/day, respectively. At 10 and 25 months of age, glucose transporter protein concentration was assessed in epitrochlearis and flexor digitorum brevis muscles with a polyclonal antibody directed against the GLUT4 transporter isoform. GLUT4 protein concentration was not altered by the aging process (i.e., comparing 10- and 25-month-old rats) in either muscle type. Wheel running increased GLUT4 protein concentration by 45% in epitrochlearis muscles of 10-month-old rats relative to age-matched sedentary controls. The training-induced adaptation in GLUT4 protein was no longer present at age 25 months, probably because the running distance had declined by 50%. In the flexor digitorum brevis, exercise did not alter GLUT4 concentration at either 10 or 25 months, presumably due to insufficient recruitment of this muscle during wheel running as assessed by measurement of citrate synthase and hexokinase enzyme activities. Wheel running induced cardiac and soleus muscle hypertrophy in 10- and 25-month-old rats. In summary, voluntary wheel running can induce an increase in skeletal muscle GLUT4 protein concentration in adult rats. Older rats that run less exhibit cardiac and soleus muscle hypertrophy, but do not maintain an elevated GLUT4 protein concentration in the epitrochlearis muscle. Aging does not alter GLUT4 protein concentration in the epitrochlearis or FDB muscles.

Aging↗
PubMed2003

Regulatory sequence elements of mouse GLUT4 gene expression in adipose tissues.

Ablation of GLUT4 in adipose tissues results in whole body insulin resistance and high-fat feeding down-regulates GLUT4 mRNA in white adipose tissues. Previous studies demonstrated that adipose tissue specific element(s) (ASE) of the murine GLUT4 gene is located between -551 and -442 relative to transcription start site and that high-fat responsive element(s) (HFRE) for down-regulation of the GLUT4 gene is located between bases -1001 and -442. To further characterize these regulatory elements, the regulation of GLUT4 minigenes containing -701, -551, and -506 bp of 5(')-flanking region was studied in transgenic mice. GLUT4 minigene mRNA from -506 transgenic mice did not express in adipose tissues, indicating that ASE located within 45 bp is located between bases -551 and -506. An 80-kDa of nuclear DNA binding protein was found to bind to a -TCCTCGTGGGAAGCG- element located between bases -551 and -537. High-fat diet feeding down-regulated GLUT4 minigene mRNA in -701 transgenic mice, but not in -551 transgenic mice, indicating that HFRE is located within 150 bp between bases -701 and -551 of the GLUT4 gene and is distinct from ASE.

Adipose Tissue↗
PubMed2004

Nuclear factor 1 regulates adipose tissue-specific expression in the mouse GLUT4 gene.

Previous studies demonstrated that an adipose tissue-specific element(s) (ASE) of the murine GLUT4 gene is located between -551 and -506 in the 5'-flanking sequence and that a high-fat responsive element(s) for down-regulation of the GLUT4 gene is located between bases -701 and -552. A binding site for nuclear factor 1 (NF1), that mediates insulin and cAMP-induced repression of GLUT4 in 3T3-L1 adipocytes is located between bases -700 and -688. To examine the role of NF1 in the regulation of GLUT4 gene expression in white adipose tissues (WAT) in vivo, we created two types of transgenic mice harboring mutated either 5' or 3' half-site of NF1-binding sites in GLUT4 minigene constructs. In both cases, the GLUT4 minigene was not expressed in WAT, while expression was maintained in brown adipose tissue, skeletal muscle, and heart. This was an unexpected finding, since a -551 GLUT4 minigene that did not have the NF1-binding site was expressed in WAT. We propose a model that explains the requirement for both the ASE and the NF1-binding site for expression of GLUT4 in WAT.

Adipose Tissue↗
PubMed2006

Syntaxin 16 controls the intracellular sequestration of GLUT4 in 3T3-L1 adipocytes.

The regulated delivery of Glut4-containing vesicles to the plasma membrane is a specialised example of regulated membrane trafficking. Present models favour the transporter trafficking through two inter-related endosomal cycles. The first is the proto-typical endosomal system. This is a fast trafficking event that, in the absence of insulin, serves to internalise Glut4 from the plasma membrane. Once in this pathway, Glut4 is further sorted into a slowly recycling pathway that operates between recycling endosomes, the trans Golgi network, and a population of vesicles often referred to as Glut4-storage vesicles. Little is known about the molecules that regulate these distinct sorting steps. Here, we have studied the role of Stx16 in Glut4 trafficking. Using two independent strategies, we show that Stx16 plays a crucial role in Glut4 traffic in 3T3-L1 adipocytes. Over-expression of a mutant form of Stx16 devoid of a transmembrane anchor was found to significantly slow the reversal of insulin-stimulated glucose transport. Depletion of Stx16 using antisense approaches profoundly reduced insulin-stimulated glucose transport but was without effect on cell surface transferrin receptor levels, and also reduced the extent of Glut4 translocation to the plasma membrane in response to insulin. These data support a model in which Stx16 is crucial in the sorting of Glut4 from the fast cycling to the slow cycling intracellular trafficking pathways in adipocytes.

3T3-L1 Cells↗
PubMed2006

Rabs 8A and 14 are targets of the insulin-regulated Rab-GAP AS160 regulating GLUT4 traffic in muscle cells.

Insulin causes translocation of glucose transporter GLUT4 to the membrane of muscle and fat cells, a process requiring Akt activation. The Rab GTPase-activating protein (Rab-GAP) AS160 is inhibited upon phosphorylation by insulin-activated Akt, thereby allowing GLUT4 translocation. Although several Rab proteins are detected on GLUT4 vesicles, the target Rabs of AS160 involved in the GLUT4 translocation have not been identified. We test whether Rabs 8A, 10, and 14 (in vitro targets of AS160) rescue the inhibition of GLUT4 translocation caused by 'constitutively active' 4P-AS160 in L6 muscle cells. Coexpression of GFP-tagged Rabs 8A or Rab14 with 4P-AS160 prevented the inhibition of GLUT4 translocation imposed by 4P-AS160. GFP-tagged, constitutively active Rab8A also elicited this rescue. In contrast, neither wild-type nor constitutively active GFP-tagged Rab10 restored GLUT4 translocation. These results suggest that Rab8A and possibly Rab14 may be targets of AS160 leading to GLUT4 translocation in L6 muscle cells.

Animals↗
PubMed2005

NF-kappaB, MEF2A, MEF2D and HIF1-a involvement on insulin- and contraction-induced regulation of GLUT4 gene expression in soleus muscle.

The GLUT4 gene transcriptional activity has a profound impact on the insulin-mediated glucose disposal and it is, therefore, important to understand the mechanisms underlying it. Insulin and exercise modulate GLUT4 expression in vivo, but the net control and involved mechanisms of each one have not been established yet. This paper sought to discriminate, in soleus muscle, the effects of insulin and muscle contraction on GLUT4 gene expression, and the involvement of transcriptional factors: myocite enhancer factor 2 (MEF2 A/C/D), hypoxia inducible factor 1-a (HIF1-a) and nuclear factor-kappa B (NF-kappaB). The GLUT4 mRNA was reduced by fasting (40%), and increased by in vitro incubation with insulin (25%) or insulin plus glucose (40%), which was accompanied by opposite regulations of NF-kappaB mRNA. Differently, in vitro, muscle contraction led to a rapid increase (35-80%) in GLUT4, MEF2A, MEF2D and HIF1-a mRNAs. Additionally, electrophoretic mobility shift assay confirmed changes in the binding activity of nuclear proteins to consensus NF-kappaB, GLUT4-Ebox and GLUT4-AT-rich element probes, parallel to the mRNA changes of their respective transcriptional factors NF-kappaB, HIF1-a and MEF2s. Concluding, insulin- and contraction-induced regulation of GLUT4 expression involves distinct transcriptional factors.

Animals↗
PubMed2003

Cadmium induces impaired glucose tolerance in rat by down-regulating GLUT4 expression in adipocytes.

Cadmium (Cd) has been known to cause hyperglycemia with diabetes-related complications in experimental animals; however, the molecular basis underlying this Cd-induced hyperglycemia is not known. Here, we report the novel finding that the impaired glucose tolerance (IGT) in rats induced by CdCl(2) is accompanied by a drastic (by as much as 90%) and dose-dependent reduction in GLUT4 protein and GLUT4 mRNA levels in adipocytes. The effect was specific to GLUT4; neither GLUT1 nor insulin-responsive aminopeptidase in adipocytes was affected. GLUT2 in hepatocytes was also not affected. Interestingly, the effect on GLUT4 was also specific to adipocytes; the muscle tissues of the Cd-treated rats showed only a slight (<25%) reduction in GLUT4 protein level with no change in GLUT4 message level, and again with no change in GLUT1 protein and its message levels. Although the insulin-induced GLUT4 translocation in adipocytes was not affected by the Cd treatment, the 3-O-methy-D-glucose flux in insulin-stimulated adipocytes of Cd-treated rat was drastically reduced. Together these findings clearly demonstrate that Cd induces IGT in rats by selectively down-regulating GLUT4 expression in adipocytes.

3-O-Methylglucose↗
PubMed2002

The fatty acid translocase (FAT)/CD36 and the glucose transporter GLUT4 are localized in different cellular compartments in rat cardiac muscle.

The fatty acid translocase (FAT)/CD36 plays an important role in the acute regulation of fatty acid uptake in muscle tissue. We studied the subcellular distribution of FAT/CD36 in rat cardiac muscle after in vivo insulin stimulation by membrane fractionation and immunoisolation of GLUT4- and FAT/CD36-vesicles. FAT/CD36 was equally present in both plasma and microsomal membranes with no effect of insulin on the cellular distribution, whereas GLUT4 increased 2- to 3-fold in the plasma membrane. FAT/CD36 resides in one intracellular pool, whereas GLUT4 is present in two distinct pools. Immunoadsorption of GLUT4-vesicles indicated that FAT/CD36 is undetectable in these vesicles. Likewise, no GLUT4 could be detected in FAT/CD36-vesicles. These vesicles contain a high amount of Rab11 that remained unaffected after insulin stimulation, whereas Rab11 increased about 3-fold in the GLUT4-vesicles in response to insulin. These data show that GLUT4 and FAT/CD36 do not co-localize in cardiac muscle and that FAT/CD36 is not redistributed in response to insulin in the heart. Rab11 may be involved in endosomal recycling of FAT/CD36, however, insulin-associated Rab11 functions appear to be limited to GLUT4-vesicles.

Animals↗
PubMed1998

GLUT4 glucose transporter expression in rodent brain: effect of diabetes.

This study describes the regional and cellular expression of the insulin-sensitive glucose transporter, GLUT4, in rodent brain. A combination of in situ hybridization, immunohistochemistry and immunoblot techniques was employed to localize GLUT4 mRNA and protein to the granule cells of the olfactory bulb, dentate gyrus of the hippocampus and the cerebellum, with the greatest level of expression being in the cerebellum. Estimates of the concentration of GLUT4 in cerebellar membranes indicate that this transporter isoform is present in significant amounts, relative to the other isoforms, GLUT1 and GLUT3. Cerebellar GLUT4 expression was increased in the genetically diabetic, hyperinsulinemic, db/db mouse relative to the non-diabetic control, and even higher levels were observed in db/db female than db/db male mice. Levels of expression of GLUT4 protein in cerebellum appear to respond to the level of circulating insulin, and are reduced in the hypoinsulinemic streptozotocin-diabetic rat. Exercise training also results in reduced insulin levels and comparably reduced levels of GLUT4 in the cerebellum. These studies demonstrate a chronic insulin-sensitive regulation of GLUT4 in rodent brain and raise the possibility of acute modulations of glucose uptake in these GLUT4 expressing cells.

Animals↗