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PubMed1999

A transcriptional repressor regulates mouse GLUT4 gene expression during the differentiation of 3T3-L1 cells.

GLUT4, the major glucose transporter in adipose tissue, is expressed during the differentiation of 3T3-L1 cells from preadipocytes to adipocytes. We previously examined the mouse GLUT4 promoter activity up to -590 bp, and demonstrated that the 5'-flanking region of the GLUT4 gene between -200 and -100 bp contains sequences that act as a repressor in preadipocytes, but not in adipocytes. Here we examine in detail the activity of this repressor in 3T3-L1 cells. Transient transfections indicated that the region extending from -125 to -112 bp functions as a repressor element only in preadipocytes. In electrophoretic mobility shift assay (EMSA), this GLUT4 repressor element (G4RE) generated specific bands with nuclear extracts from preadipocytes, but not from adipocytes. Southwestern blot analysis identified a protein of approximately 96 kDa from preadipocytes that bound to the G4RE site. Mutation of the G4RE site, which abolished the protein/DNA complex formation by EMSA, increased GLUT4 promoter activity only in preadipocytes. These results suggest that the G4RE site and its binding protein may regulate GLUT4 gene transcription during adipocyte differentiation.

3T3 Cells↗
PubMed2000

Sustained activation of insulin receptors internalized in GLUT4 vesicles of insulin-stimulated skeletal muscle.

Exposure of target cells to insulin results in the formation of ligand receptor complexes on the cell surface and their subsequent internalization into the endosomal apparatus. A current view is that endocytosis of the insulin receptor (IR) kinase results in its rapid deactivation and sorting of the IR back to the cell surface or to late endocytic compartments. We report herein that, in skeletal muscle, in vivo stimulation with insulin induced a rapid internalization of the IR to an insulin-sensitive GLUT4-enriched intracellular membrane fraction. After 30 min of stimulation, IR content and tyrosine phosphorylation were increased by three and nine times in that fraction, respectively, compared with unstimulated muscles. In vitro autophosphorylation assays revealed that the kinase activity of internalized IRs was markedly augmented (eight to nine times) by insulin. In marked contrast with hepatic endosomes or adipocyte low-density microsomes, no IR tyrosine dephosphorylation activity was observed in GLUT4-enriched vesicles isolated from skeletal muscle. The activated IR was recovered in immunopurified GLUT4 vesicles after insulin stimulation. Insulin also increased tyrosine-phosphorylated insulin receptor substrate 1 and phosphatidylinositol 3-kinase adapter (p85) subunit contents in the intracellular membrane fraction, but these signaling molecules were not directly associated with GLUT4 vesicles. These results show that, in skeletal muscle, the activated IR reaches a GLUT4-enriched compartment where its activity is apparently sustained. We propose that compartmentalization of activated IRs to GLUT4 vesicles may play a role in sustaining insulin signaling at this locus in skeletal muscle.

Animals↗
PubMed2001

Troglitazone induces GLUT4 translocation in L6 myotubes.

A number of studies have demonstrated that insulin resistance in the skeletal muscle plays a pivotal role in the insulin resistance associated with obesity and type 2 diabetes. A decrease in GLUT4 translocation from the intracellular pool to the plasma membranes in skeletal muscles has been implicated as a possible cause of insulin resistance. Herein, we examined the effects of an insulin-sensitizing drug, troglitazone (TGZ), on glucose uptake and the translocation of GLUT4 in L6 myotubes. The prolonged exposure (24 h) of L6 myotubes to TGZ (10(-5) mol/l) caused a substantial increase in the 2-deoxy-[3H]D-glucose (2-DG) uptake without changing the total amount of the glucose transporters GLUT4, GLUT1, and GLUT3. The TGZ-induced 2-DG uptake was completely abolished by cytochalasin-B (10 micromol/l). The ability of TGZ to translocate GLUT4 from light microsomes to the crude plasma membranes was greater than that of insulin. Both cycloheximide treatment (3.5 x 10(-6) mol/l) and the removal of TGZ by washing reversed the 2-DG uptake to the basal level. Moreover, insulin did not enhance the TGZ-induced 2-DG uptake additively. The TGZ-induced 2-DG uptake was only partially reversed by wortmannin to 80%, and TGZ did not change the expression and the phosphorylation of protein kinase B; the expression of protein kinase C (PKC)-lambda, PKC-beta2, and PKC-zeta; or 5'AMP-activated protein kinase activity. a-Tocopherol, which has a molecular structure similar to that of TGZ, did not increase 2-DG uptake. We conclude that the glucose transport in L6 myotubes exposed to TGZ for 24 h is the result of an increased translocation of GLUT4. The present results imply that the effects of troglitazone on GLUT4 translocation may include a new mechanism for improving glucose transport in skeletal muscle.

Animals↗
PubMed2003

5-amino-imidazole carboxamide riboside increases glucose transport and cell-surface GLUT4 content in skeletal muscle from subjects with type 2 diabetes.

AMP-activated protein kinase (AMPK) activation by AICAR (5-amino-imidazole carboxamide riboside) is correlated with increased glucose transport in rodent skeletal muscle via an insulin-independent pathway. We determined in vitro effects of insulin and/or AICAR exposure on glucose transport and cell-surface GLUT4 content in skeletal muscle from nondiabetic men and men with type 2 diabetes. AICAR increased glucose transport in a dose-dependent manner in healthy subjects. Insulin and AICAR increased glucose transport and cell-surface GLUT4 content to a similar extent in control subjects. In contrast, insulin- and AICAR-stimulated responses on glucose transport and cell-surface GLUT4 content were impaired in subjects with type 2 diabetes. Importantly, exposure of type 2 diabetic skeletal muscle to a combination of insulin and AICAR increased glucose transport and cell-surface GLUT4 content to levels achieved in control subjects. AICAR increased AMPK and acetyl-CoA carboxylase phosphorylation to a similar extent in skeletal muscle from subjects with type 2 diabetes and nondiabetic subjects. Our studies highlight the potential importance of AMPK-dependent pathways in the regulation of GLUT4 and glucose transport activity in insulin-resistant skeletal muscle. Activation of AMPK is an attractive strategy to enhance glucose transport through increased cell surface GLUT4 content in insulin-resistant skeletal muscle.

Aminoimidazole Carboxamide↗
PubMed2003

Regulation of GLUT4 traffic and function by insulin and contraction in skeletal muscle.

Glucose transport across the cell surface is a key regulatory step for glucose metabolism in skeletal muscle. Both insulin and exercise increase glucose transport into myofibers through glucose transporter (GLUT) proteins. Skeletal muscle expresses several members of the GLUT family but the GLUT4 glucose transporter is considered the main "regulatable" isoform that is modulated by insulin and contraction. Glucose transport rate can be stimulated either by recruitment of GLUT4 units from intracellular storage vesicles or through activation of cell surface transporters. Insulin activates GLUT4 translocation through a complex signaling cascade involving both the lipid kinase phosphatidylinositol 3-kinase and the proto-oncoprotein c-Cbl. Contraction, on the other hand, appears to trigger GLUT4 translocation at least in part through activation of the metabolite-sensing 5'-AMP-activated protein kinase. Furthermore, recent studies suggest that p38 MAP kinase activation represents a point of convergence of the signaling pathways utilized by insulin and contraction to increase GLUT4 activation at the cell surface. This review will summarize our current knowledge of these alternative pathways of GLUT4 regulation in skeletal muscle.

Animals↗
PubMed2004

[Effects of puerarin on plasma membrane GLUT4 content in skeletal muscle from insulin-resistant Sprague-Dawley rats under insulin stimulation].

OBJECTIVE: To explore the effect of puerarin injection on the amount of GLUT4 protein at the plasma membrane in insulin-resistant rat skeletal muscle. METHOD: The rat model of insulin resistance (IR) was made by being fed with high-fat diet. The animals were divided into three groups (ten in each group): group I: controls; group II: Insulin-resistant rats; group III: Insulin-resistant rats + Puerarin treatment. Insulin-resistant rats were injected with 100 mg puerarin injection per kg body weight through abdominal cavity once a day for 4 weeks. Fasting blood glucose and fasting serum insulin levels were measured before and after Puerarin treatment, respectively. Insulin treatment was achieved by intraperitoneal injection of insulin (1 unit insulin per kg body weight.) 15 minute before killing the animals. The right hindlimb skeletal muscle was rapidly dissected. Then the expression of GLUT4 protein at the plasma membrane in all the animals was assessed with Western blot method. RESULT: The GLUT4 content at the plasma membrane in insulin-resistant rats skeletal muscle was significantly lower (about 31%) than that of controls (P < 0.01). Puerarin Injection partly corrected fasting blood glucose (from 6.17 +/- 0.67 mmol x L(-1) to 5.54 +/- 0.35 mmol x L(-1)) and fasting serum insulin levels (from 17.09 +/- 2.02 mU x L(-1) to 11.86 +/- 1.35 mU x L(-1)) and increased the GLUT4 content at the plasma membrane by 1.18-fold in insulin-resistant rats skeletal muscle. CONCLUSION: Puerarin Injection can ameliorate IR, and the mechanism may be involved in increasing cell-surface level of GLUT4 through decreasing fasting blood glucose and fasting serum insulin levels, improving GLUT4 trafficking and intracellular insulin signaling.

Animals↗
PubMed1991

Differentiation of erythrocyte-(GLUT1), liver-(GLUT2), and adipocyte-type (GLUT4) glucose transporters by binding of the inhibitory ligands cytochalasin B, forskolin, dipyridamole, and isobutylmethylxanthine.

The binding affinities of the glucose transporter isoforms GLUT1, GLUT2, and GLUT4 for the inhibitory ligands cytochalasin B, forskolin, dipyridamole, and isobutylmethylxanthine (IBMX) were compared in membranes from human erythrocytes and rat brain containing the erythrocyte-type glucose transporter (GLUT1), in membranes from rat liver containing the liver-type glucose transporter (GLUT2), and in membranes from adipocytes and heart containing predominantly the adipose/muscle-type glucose transporter (GLUT4). The binding affinities of cytochalasin B for GLUT1 and GLUT4 were virtually identical (KD) in membranes from erythrocytes, 190 nM; in brain, 130 nM; in adipocytes, 160 nM; and in heart, 170 nM). In contrast, no specific glucose-inhibitable binding of cytochalasin B was detected in liver membranes. The binding affinity for forskolin of GLUT1 was significantly lower than that of GLUT4 (KD in erythrocytes, 2360 nM; Kl in brain, 4360 nM; and KD in adipocytes, 200 nM; and in heart, 210 nM); specific glucose-inhibitable binding to GLUT2 was not detectable. Like forskolin, the glucose transport inhibitors dipyridamole (Kl in adipocyte membranes, 1.2 microM; in erythrocytes, greater than 40 microM) and IMBX (Kl in adipocyte membranes, 60 microM; and in erythrocytes, greater than 500 microM) bound with higher affinity to GLUT4 than to GLUT1. These data demonstrate striking differences of GLUT1, GLUT2, and GLUT4 with respect to their binding affinity for the inhibitory ligands cytochalasin B, forskolin, dipyridamole, and IBMX. It is suggested that the complex differences result from interaction of more than one heterogeneous binding site at the glucose transporters with the inhibitory ligand.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Arachidonic acid down-regulates the insulin-dependent glucose transporter gene (GLUT4) in 3T3-L1 adipocytes by inhibiting transcription and enhancing mRNA turnover.

Chronic exposure of fully differentiated 3T3-L1 adipocytes to 50 microM arachidonic acid (AA) resulted in an inhibition (approximately 91%) in cellular GLUT4 mRNA content after a 48-h exposure, without similarly affecting the mRNA content of the ubiquitous glucose transporter, GLUT1. Subsequent investigations revealed that transcription of the GLUT4 gene was reduced by approximately 50% in response to AA treatment and the half-life of GLUT4 mRNA decreased from 8.0 to 4.6 h. By contrast, AA increased the accumulation of GLUT1 mRNA by 65%, by a mechanism that also involved regulation at both transcriptional and mRNA stability levels. Western blot analysis revealed that AA was specifically reducing the insulin-responsive glucose transporter (GLUT4) in both plasma and intracellular membranes. Subsequently, AA was observed to alter the ability of the GLUT4 transporter to respond to insulin and mediate a significant enhancement of glucose uptake. The results presented in this study indicate that AA can partially mimic the effects of both tumor necrosis factor-alpha and insulin which, when chronically supplied to 3T3-L1 adipocytes, also down-regulate GLUT4 gene expression. Therefore, these data may have relevance to the insulin-resistance associated with non-insulin-dependent diabetes mellitus.

Adipocytes↗
PubMed1993

Kinetics of GLUT1 and GLUT4 glucose transporters expressed in Xenopus oocytes.

The predominant mechanism by which insulin activates glucose transport in muscle and adipose tissue is by affecting the redistribution of the facilitated hexose carriers, GLUT1 and GLUT4, from an intracellular site to the plasma membrane. A quantitative analysis of this process has been hampered by the lack of reliable determinations for kinetic constants catalyzed by each of these isoforms. In order to obtain such information, each transporter was expressed in Xenopus oocytes by the injection of mRNA encoding rat GLUT1 or GLUT4. Equilibrium exchange 3-O-methylglucose uptake was measured and the data fitted to a two-compartment model, yielding Km = 26.2 mM and Vmax = 3.5 nmol/min/cell for GLUT1 and Km = 4.3 mM and Vmax = 0.7 nmol/min/cell for GLUT4. Measurement of the abundance of cell surface transporters was accomplished by two independent protocols: photolabeling with the impermeant hexose analog 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 -yloxy)-2-propylamine and subcellular fractionation of oocytes. Data obtained by either technique revealed that the ratio of plasma membrane GLUT1 to GLUT4 was about 4; this paralleled the relative maximal velocities for hexose transport, indicating that the turn-over numbers for the two isoforms were the same. Moreover, measurement of the concentration of exofacially disposed transporters with 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 -yloxy)-2-propylamine allowed calculation of the turnover number to be about 20,000 min-1. These data indicate that, at low substrate concentrations, the catalytic efficiency of GLUT4 is significantly greater than GLUT1. Extrapolation to mammalian systems suggests that GLUT4 is responsible for virtually all of the hexose uptake in insulin-responsive targets, particularly in the presence of hormone.

3-O-Methylglucose↗
PubMed1995

Decreased glucose transporter protein (GLUT4) in skeletal muscle of hypertriglyceridaemic insulin-resistant rat.

Protein levels (Western blot) of the major glucose transporter isoform (GLUT4) were measured in skeletal muscles (quadriceps femoris) of an animal model of human metabolic syndrome X, i.e. the hereditary hypertriglyceridaemic (HTG) insulin-resistant rats fed various diets. The results were compared with the data obtained in normal Wistar rats which underwent the identical protocol. In HTG rats fed the basal diet (B) or high-sucrose diet (HS) (known to induce hypertriglyceridaemia and to impair insulin action), a decrease of GLUT4 protein levels (B: Control 100 +/- 3 vs HTG 46 +/- 5%, p < 0.005; HS: Control 80 +/- 9 vs HTG 49 +/- 3%, p < 0.005) was observed. Furthermore, marine fish oil (FO) rich in n-3 polyunsaturated fatty acids (PUFA), added to the basal diet (30 wt % of n-3 PUFA) reduced the GLUT4 protein levels (B: 100 +/- 3 vs B+FO: 42 +/- 4%, p < 0.005) in control rats to values similar to those found in HTG rats (B: 46 +/- 4%). However, dietary FO did not have any effect in HTG rats (49 +/- 3%). Feeding the high-sucrose diet supplemented with FO to both the control and HTG rats was followed by a further decrement of GLUT4 protein (Control 15 +/- 5 vs HTG 14 +/- 4%). In conclusions, a) the hereditary HTG rats had by about 50% lower GLUT4 protein levels in the quadriceps femoris muscle in comparison to normal Wistar rats; b) high-sucrose diet or raised dietary intake of n-3 PUFA did not further alter the number of glucose carriers in quadriceps femoris muscle in HTG rats and c) feeding the high-sucrose diet with higher proportion of n-3 PUFA was associated with an additional reduction of the GLUT4 protein level in this muscle.

Animals↗
PubMed1993

Cyclic AMP-induced transcriptional repression of the insulin-responsive glucose transporter (GLUT4) gene: identification of a promoter region required for down-regulation of transcription.

The mechanism(s) by which cyclic AMP represses transcription of the GLUT4 gene was investigated. 3T3-L1 preadipocytes were stably transfected with a series of 5' deletion mutants of the mouse GLUT4 gene promoter fused to the bacterial CAT gene and then were induced to differentiate into adipocytes. A method based on reverse transcription/polymerase chain reaction (PCR) amplification was developed and optimized to quantitate expression of CAT mRNA transcripts. Treatment with 8-bromo-cAMP down-regulated the level of CAT mRNA in adipocytes transfected with the -7000/CAT, -785/CAT and -469/CAT constructs, but not the -78/CAT construct. Thus, the regulatory element(s) which mediates transcriptional repression by cAMP resides in the proximal promoter of the GLUT4 gene between positions -469 and -78. Since down-regulation of GLUT4 mRNA is unaffected by inhibitors of protein synthesis, cAMP (and insulin) may activate phosphorylation or dephosphorylation of an existing transcription factor that interacts with the GLUT4 proximal promoter.

3T3 Cells↗
PubMed1994

Epidermal growth factor triggers the translocation of insulin-responsive glucose transporter (GLUT4).

In a novel cell line we developed for direct, sensitive detection of insulin-responsive glucose transporter (GLUT4) on the cell surface, we considered that insulin-activated phosphatidylinositol 3-kinase (PI 3-kinase) may be involved in the signaling pathway of insulin-stimulated GLUT4 translocation. We report here evidence that epidermal growth factor (EGF), which stimulates PI 3-kinase activity, also triggers GLUT4 translocation in Chinese hamster ovary (CHO) cells stably overexpressing the EGF receptor. The EGF-dependent GLUT4 translocation is possibly mediated by two independent pathways: one by PI 3-kinase and the other by protein kinase C (PKC); the PI 3-kinase-mediated pathway predominates. Triggering of the GLUT4 translocation is not specific for insulin, rather it may be a common property of growth factors which activate PI 3-kinase.

Androstadienes↗
PubMed1997

Regulatory elements in the insulin-responsive glucose transporter (GLUT4) gene.

GLUT4, the insulin responsive-glucose transporter, mediates the rate limiting step of glucose metabolism in skeletal muscle and adipose tissue. GLUT4 expression is up-regulated by exercise training and thyroid hormone treatment and is down-regulated by fasting, streptozotocin-induced diabetes, obesity, high-fat diet, and denervation. Since overexpression of GLUT4 in insulin resistant db/db mice and high-fat diet-fed mice has been observed to dramatically improve glycemic control, increasing GLUT4 expression may be an effective strategy with which to alleviate insulin resistance. This review discusses recent findings on the regulation of the GLUT4 gene and on progress in the identification of regulatory elements in the promoter of the gene.

Adipose Tissue↗
PubMed1999

Overexpression of protein tyrosine phosphatase-alpha (PTP-alpha) but not PTP-kappa inhibits translocation of GLUT4 in rat adipose cells.

Protein tyrosine phosphatases (PTPases) are likely to play important roles in insulin action. We recently demonstrated that the nontransmembrane PTPase PTP1B can act as a negative modulator of insulin-stimulated translocation of GLUT4. We now examine the role of PTP-alpha and PTP-kappa (two transmembrane PTPases) in this metabolic action of insulin. Rat adipose cells were transfected with either PTP-alpha or PTP-kappa and effects of these PTPases on the translocation of a cotransfected epitope-tagged GLUT4 were studied. Cells overexpressing wild-type PTP-alpha had significantly lower levels of cell surface GLUT4 in response to insulin and a threefold decrease in insulin sensitivity when compared with control cells expressing only tagged GLUT4. Co-overexpression of PTP-alpha and PTP1B did not have additive effects, suggesting that these PTPases share common substrates. Cells overexpressing either wild-type PTP-kappa or catalytically inactive mutants of PTP-alpha had dose-response curves similar to those of control cells. Since overexpression of PTP-alpha, but not PTP-kappa, had effects on translocation of GLUT4, our data suggest that PTPalpha may be a specific negative modulator of insulin-stimulated glucose transport.

Adipocytes↗
PubMed2001

PTEN does not modulate GLUT4 translocation in rat adipose cells under physiological conditions.

PTEN is a 3'-inositol lipid phosphatase that dephosphorylates products of PI 3-kinase. Since PI 3-kinase is required for many metabolic actions of insulin, we investigated the role of PTEN in insulin-stimulated translocation of GLUT4. In control rat adipose cells, we observed a approximately 2-fold increase in cell surface GLUT4 upon maximal insulin stimulation. Overexpression of wild-type PTEN abolished this response to insulin. Translocation of GLUT4 in cells overexpressing PTEN mutants without lipid phosphatase activity was similar to that observed in control cells. Overexpression of PTEN-CBR3 (mutant with disrupted membrane association domain) partially impaired translocation of GLUT4. In Cos-7 cells, overexpression of wild-type PTEN had no effect on ERK2 phosphorylation in response to acute insulin stimulation. However, Elk-1 phosphorylation in response to chronic insulin treatment was significantly decreased. Thus, when PTEN is overexpressed, both its lipid phosphatase activity and subcellular localization play a role in antagonizing metabolic actions of insulin that are dependent on PI 3-kinase but independent of MAP kinase. However, because translocation of GLUT4 in cells overexpressing a dominant inhibitory PTEN mutant (C124S) was similar to that of control cells, we conclude that endogenous PTEN may not modulate metabolic functions of insulin under normal physiological conditions.

3T3 Cells↗
PubMed2001

A novel functional co-operation between MyoD, MEF2 and TRalpha1 is sufficient for the induction of GLUT4 gene transcription.

We report tripartite co-operation between MyoD, myocyte enhancer factor-2 (MEF2) and the thyroid hormone receptor (TRalpha1) that takes place in the context of an 82-bp muscle-specific enhancer in the rat insulin-responsive glucose transporter (GLUT4) gene that is active in both cardiac and skeletal muscle. In the L6E9 skeletal muscle cell line and in 10T1/2 fibroblasts, a powerful synergistic activation of the GLUT4 enhancer relied on the over-expression of MyoD, MEF2 and TRalpha1 and the integrity of their respective binding sites, and occurred when linked to either a heterologous promoter or in the context of the native GLUT4 promoter. In cardiac myocytes, enhancer activity was dependent on the binding sites for MEF2 and TRalpha1. Furthermore, we show that in 10T1/2 fibroblasts, the forced expression of MyoD, MEF2 and TRalpha1 induced the expression of the endogenous, otherwise silent, GLUT4 gene. In all, our results indicate a novel functional co-operation between these three factors which is required for full activation of GLUT4 transcription.

Animals↗
PubMed2005

Effect of exercise on the expression of adiponectin mRNA and GLUT4 mRNA in type 2 diabetic rats.

To investigate the impact of exercise on the expression of adiponectin and GLUT4 mRNA in type 2 diabetic rats, type 2 diabetic rat model was made. The diabetic rats were treated with swimming training for 8 weeks. The expression of adiponectin mRNA in perirenal fat and GLUT4 mRNA in skeletal muscles were assessed by reverse transcription polymerase chain reaction (RT-PCR) and the levels of blood glucose, serum insulin, and blood lipid were measured. Our results showed that the expression of adiponectin mRNA and GLUT4 mRNA in diabetic model group was decreased by 45% (P < 0.01), 43% (P < 0.01) respectively. The gene expression of adiponectin and GLUT4 was increased significantly in swimming group (P < 0.05 and P < 0.01, respectively). Compared with the model group, fasting insulin, TG, TC and FFA were decreased significantly in the training group (P < 0.05 or P < 0.01) as compared with model group. It is concluded that exercise can promote the expression of adiponectin mRNA and GLUT4 mRNA in type 2 diabetic rats, which may be one of the mechanisms responsible for the amelioration of insulin resistance in the rats.

Adiponectin↗
PubMed1999

Increased diaphragm expression of GLUT4 in control and streptozotocin-diabetic rats by fish oil-supplemented diets.

Dietary fat intake influences plasma glucose concentration through modifying glucose uptake and utilization by adipose and skeletal muscle tissues. In this paper, we studied the effects of a low-fat diet on diaphragm GLUT4 expression and fatty acid composition in control and streptozotocin-induced diabetic rats. Control as well as diabetic rats were divided into three different dietary groups each. Either 5% olive oil, 5% sunflower oil, or 5% fish oil was the only fat supplied by the diet. Feeding these low-fat diets for 5 wk induced major changes in fatty acid composition, both in control and in diabetic rats. Arachidonic acid was higher in diabetic olive and sunflower oil-fed rats with respect to fish oil-fed, opposite to docosahexaenoic acid which was higher in diabetic fish oil-fed rats with respect to the other two groups. Animals receiving a fish oil diet had the lowest plasma glucose concentration. GLUT4 expression in diaphragm, as indicated by GLUT4 protein and mRNA, is modulated both by diabetes and by diet fatty acid composition. Diabetes induced a decrease in expression in all dietary groups. Plasma glucose levels correlated well with the increased amount of GLUT4 protein and mRNA found in fish oil-fed groups. Results are discussed in terms of the influence that arachidonic and n-3 polyunsaturated fatty acids may exert on the transcriptional and translational control of the GLUT4 gene.

Animals↗