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Thorkil Ploug

Publications and source records attributed to Thorkil Ploug.

18 recordsLinked to original sources
PubMed2006

Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine.

A better understanding of skeletal muscle lipid metabolism is needed to identify the molecular mechanisms relating intramuscular triglyceride (IMTG) to muscle metabolism and insulin sensitivity. An increasing number of proteins have been reported to be associated with intracellular triglyceride (TG), among them the PAT family members: perilipin, ADRP (for adipocyte differentiation-related protein), and TIP47 (for tail-interacting protein of 47 kDa). Hormone-sensitive lipase (HSL) is thought to be the major enzyme responsible for IMTG hydrolysis in skeletal muscle. In adipocytes, regulation of HSL by intracellular redistribution has been demonstrated. The existence of such regulatory mechanisms in skeletal muscle has long been hypothesized but has never been demonstrated. The aim of this study was to characterize the PAT family proteins associated with IMTG and to investigate the effect of epinephrine stimulation or muscle contraction on skeletal muscle TG content and HSL intracellular distribution. Rat soleus muscles were either incubated with epinephrine or electrically stimulated for 15 min. Single muscle fibers were used for morphological analysis by confocal and transmission electron microscopy. We show a decrease in IMTG in response to both lipolytic stimuli. Furthermore, we identify two PAT family proteins, ADRP and TIP47, associated with IMTG. Finally, we demonstrate HSL translocation to IMTG and ADRP after stimulation with epinephrine or contraction.

Animals↗
PubMed2006

Early and rapid development of insulin resistance, islet dysfunction and glucose intolerance after high-fat feeding in mice overexpressing phosphodiesterase 3B.

Inadequate islet adaptation to insulin resistance leads to glucose intolerance and type 2 diabetes. Here we investigate whether beta-cell cAMP is crucial for islet adaptation and prevention of glucose intolerance in mice. Mice with a beta-cell-specific, 2-fold overexpression of the cAMP-degrading enzyme phosphodiesterase 3B (RIP-PDE3B/2 mice) were metabolically challenged with a high-fat diet. We found that RIP-PDE3B/2 mice early and rapidly develop glucose intolerance and insulin resistance, as compared with wild-type littermates, after 2 months of high-fat feeding. This was evident from advanced fasting hyperinsulinemia and early development of hyper-glycemia, in spite of hyperinsulinemia, as well as impaired capacity of insulin to suppress plasma glucose in an insulin tolerance test. In vitro analyses of insulin-stimulated lipogenesis in adipocytes and glucose uptake in skeletal muscle did not reveal reduced insulin sensitivity in these tissues. Significant steatosis was noted in livers from high-fat-fed wild-type and RIP-PDE3B/2 mice and liver triacyl-glycerol content was 3-fold higher than in wild-type mice fed a control diet. Histochemical analysis revealed severe islet perturbations, such as centrally located alpha-cells and reduced immunostaining for insulin and GLUT2 in islets from RIP-PDE3B/2 mice. Additionally, in vitro experiments revealed that the insulin secretory response to glucagon-like peptide-1 stimulation was markedly reduced in islets from high-fat-fed RIP-PDE3B/2 mice. We conclude that accurate regulation of beta-cell cAMP is necessary for adequate islet adaptation to a perturbed metabolic environment and protective for the development of glucose intolerance and insulin resistance.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Imaging of insulin signaling in skeletal muscle of living mice shows major role of T-tubules.

Insulin stimulates glucose transport in skeletal muscle by glucose transporter GLUT4 translocation to sarcolemma and membrane invaginations, the t-tubules. Although muscle glucose uptake plays a key role in insulin resistance and type 2 diabetes, the dynamics of GLUT4 translocation and the signaling involved are not well described. We have now developed a confocal imaging technique to follow trafficking of green fluorescent protein-labeled proteins in living muscle fibers in situ in anesthetized mice. Using this technique, by imaging the dynamics of GLUT4 translocation and phosphatidylinositol 3,4,5 P(3) (PIP(3)) production in response to insulin, here, for the first time, we delineate the temporal and spatial distribution of these processes in a living animal. We find a 10-min delay of maximal GLUT4 recruitment and translocation to t-tubules compared with sarcolemma. Time-lapse imaging of a fluorescent dye after intravenous injection shows that this delay is similar to the time needed for insulin diffusion into the t-tubule system. Correspondingly, immunostaining of muscle fibers shows that insulin receptors are present throughout the t-tubule system. Finally, PIP(3) production, an early event in insulin signaling, progresses slowly along the t-tubules with a 10-min delay between maximal PIP(3) production at sarcolemma compared with deep t-tubules following the appearance of dye-labeled insulin. Our findings in living mice indicate a major role of the t-tubules in insulin signaling in skeletal muscle and show a diffusion-associated delay in insulin action between sarcolemma and inner t-tubules.

Animals↗
PubMed2005

Effect of intermittent fasting and refeeding on insulin action in healthy men.

Insulin resistance is currently a major health problem. This may be because of a marked decrease in daily physical activity during recent decades combined with constant food abundance. This lifestyle collides with our genome, which was most likely selected in the late Paleolithic era (50,000-10,000 BC) by criteria that favored survival in an environment characterized by fluctuations between periods of feast and famine. The theory of thrifty genes states that these fluctuations are required for optimal metabolic function. We mimicked the fluctuations in eight healthy young men [25.0 +/- 0.1 yr (mean +/- SE); body mass index: 25.7 +/- 0.4 kg/m(2)] by subjecting them to intermittent fasting every second day for 20 h for 15 days. Euglycemic hyperinsulinemic (40 mU.min(-1).m(-2)) clamps were performed before and after the intervention period. Subjects maintained body weight (86.4 +/- 2.3 kg; coefficient of variation: 0.8 +/- 0.1%). Plasma free fatty acid and beta-hydroxybutyrate concentrations were 347 +/- 18 and 0.06 +/- 0.02 mM, respectively, after overnight fast but increased (P < 0.05) to 423 +/- 86 and 0.10 +/- 0.04 mM after 20-h fasting, confirming that the subjects were fasting. Insulin-mediated whole body glucose uptake rates increased from 6.3 +/- 0.6 to 7.3 +/- 0.3 mg.kg(-1).min(-1) (P = 0.03), and insulin-induced inhibition of adipose tissue lipolysis was more prominent after than before the intervention (P = 0.05). After the 20-h fasting periods, plasma adiponectin was increased compared with the basal levels before and after the intervention (5,922 +/- 991 vs. 3,860 +/- 784 ng/ml, P = 0.02). This experiment is the first in humans to show that intermittent fasting increases insulin-mediated glucose uptake rates, and the findings are compatible with the thrifty gene concept.

Adult↗
PubMed2005

Phosphorylation-dependent translocation of glycogen synthase to a novel structure during glycogen resynthesis.

Glycogen metabolism has been the subject of extensive research, but the mechanisms by which it is regulated are still not fully understood. It is well accepted that the rate-limiting enzymes in glycogenesis and glycogenolysis are glycogen synthase (GS) and glycogen phosphorylase (GPh), respectively. Both enzymes are regulated by reversible phosphorylation and by allosteric effectors. However, evidence in the literature indicates that changes in muscle GS and GPh intracellular distribution may constitute a new regulatory mechanism of glycogen metabolism. Already in the 1960s, it was proposed that glycogen was present in dynamic cellular organelles that were termed glycosomas but no such cellular entities have ever been demonstrated. The aim of this study was to characterize muscle GS and GPh intracellular distribution and to identify possible translocation processes of both enzymes. Using in situ stimulation of rabbit tibialis anterior muscle, we show GS and GPh intracellular redistribution at the beginning of glycogen resynthesis after contraction-induced glycogen depletion. We identify a new "player," a new intracellular compartment involved in skeletal muscle glycogen metabolism. They are spherical structures that were not present in basal muscle, and we present evidence that indicate that they are products of actin cytoskeleton remodeling. Furthermore, for the first time, we show a phosphorylation-dependent intracellular distribution of GS. Here, we present evidence of a new regulatory mechanism of skeletal muscle glycogen metabolism based on glycogen enzyme intracellular compartmentalization.

Actins↗
PubMed2005

Glucose clearance is higher in arm than leg muscle in type 2 diabetes.

Insulin-mediated glucose clearance (GC) is diminished in type 2 diabetes. Skeletal muscle has been estimated to account for essentially all of the impairment. Such estimations were based on leg muscle and extrapolated to whole body muscle mass. However, skeletal muscle is not a uniform tissue and insulin resistance may not be evenly distributed. We measured basal and insulin-mediated (1 pmol min-1 kg-1) GC simultaneously in the arm and leg in type 2 diabetes patients (TYPE 2) and controls (CON) (n=6 for both). During the clamp arterio-venous glucose extraction was higher in CON versus TYPE 2 in the arm (6.9+/-1.0 versus 4.7+/-0.8%; mean+/-s.e.m.; P=0.029), but not in the leg (4.2+/-0.8 versus 3.1+/-0.6%). Blood flow was not different between CON and TYPE 2 but was higher (P<0.05) in arm versus leg (CON: 74+/-8 versus 56+/-5; TYPE 2: 87+/-9 versus 43+/-6 ml min-1 kg-1 muscle, respectively). At basal, CON had 84% higher arm GC (P=0.012) and 87% higher leg GC (P=0.016) compared with TYPE 2. During clamp, the difference between CON and TYPE 2 in arm GC was diminished to 54% but maintained at 80% in the leg. In conclusion, this study shows that glucose clearance is higher in arm than leg muscles, regardless of insulin resistance, which may indicate better preserved insulin sensitivity in arm than leg muscle in type 2 diabetes.

Arm↗
PubMed2005

Prevention of hyperglycemia in Zucker diabetic fatty rats by exercise training: effects on gene expression in insulin-sensitive tissues determined by high-density oligonucleotide microarray analysis.

Exercise training (ET) causes metabolic improvement in the prediabetic and diabetic states. However, only little information exists on the changes to ET at the transcriptional level in insulin-sensitive tissues. We have investigated the gene expression changes in skeletal muscle, liver, fat, and pancreatic islets after ET in male Zucker diabetic fatty (ZDF) rats. Eighteen ZDF rats (7 weeks old) were divided in a control and ET group. Exercise was performed using a motorized treadmill (20 m/min 1 hour daily for 6 days a week). Blood glucose, weight, and food intake were measured weekly. After 5 weeks, blood samples, soleus muscle, liver, visceral fat (epididymal fat pads), and islet tissue were collected. Gene expression was quantified with Affymetrix RG-U34A array (16 chips). Exercise training ameliorates the development of hyperglycemia and reduces plasma free fatty acid and the level of glucagon-insulin ratio (P < .05). In skeletal muscle, the expression of 302 genes increased, whereas that of 119 genes decreased. These changes involved genes related to skeletal muscle plasticity, Ca(2+) signals, energy metabolism (eg, glucose transporter 1, phosphorylase kinase), and other signaling pathways as well as genes with unknown functions (expressed sequence tags). In the liver, expression of 148 genes increased, whereas that of 199 genes decreased. These were primarily genes involved in lipogenesis and detoxification. Genes coding for transcription factors were changed in parallel in skeletal muscle and liver tissue. Training did not markedly influence the gene expression in islets. In conclusion, ET changes the expression of multiple genes in the soleus muscle and liver tissue and counteracts the development of diabetes, indicating that ET-induced changes in gene transcription may play an important role en the prevention of diabetes.

Adipose Tissue↗
PubMed2005

Hormone-sensitive lipase as mediator of lipolysis in contracting skeletal muscle.

The authors propose that the enzyme hormone-sensitive lipase (HSL), which is the rate-limiting enzyme for hydrolysis of triacylglycerol in adipocytes, also regulates the intramyocellular triacylglycerol mobilization and is controlled by mechanisms similar to those regulating glycogen phosphorylase. From an exercise perspective, it is fascinating that the primary enzymatic setting allows simultaneous mobilization of all major extramuscular and intramuscular energy stores.

Animals↗
PubMed2005

Expression profiling reveals differences in metabolic gene expression between exercise-induced cardiac effects and maladaptive cardiac hypertrophy.

While cardiac hypertrophy elicited by pathological stimuli eventually leads to cardiac dysfunction, exercise-induced hypertrophy does not. This suggests that a beneficial hypertrophic phenotype exists. In search of an underlying molecular substrate we used microarray technology to identify cardiac gene expression in response to exercise. Rats exercised for seven weeks on a treadmill were characterized by invasive blood pressure measurements and echocardiography. RNA was isolated from the left ventricle and analysed on DNA microarrays containing 8740 genes. Selected genes were analysed by quantitative PCR. The exercise program resulted in cardiac hypertrophy without impaired cardiac function. Principal component analysis identified an exercise-induced change in gene expression that was distinct from the program observed in maladaptive hypertrophy. Statistical analysis identified 267 upregulated genes and 62 downregulated genes in response to exercise. Expression changes in genes encoding extracellular matrix proteins, cytoskeletal elements, signalling factors and ribosomal proteins mimicked changes previously described in maladaptive hypertrophy. Our most striking observation was that expression changes of genes involved in beta-oxidation of fatty acids and glucose metabolism differentiate adaptive from maladaptive hypertrophy. Direct comparison to maladaptive hypertrophy was enabled by quantitative PCR of key metabolic enzymes including uncoupling protein 2 (UCP2) and fatty acid translocase (CD36). DNA microarray analysis of gene expression changes in exercise-induced cardiac hypertrophy suggests that a set of genes involved in fatty acid and glucose metabolism could be fundamental to the beneficial phenotype of exercise-induced hypertrophy, as these changes are absent or reversed in maladaptive hypertrophy.

Animals↗
PubMed2004

Contractions induce phosphorylation of the AMPK site Ser565 in hormone-sensitive lipase in muscle.

Intramyocellular triglyceride is an important energy store which is related to insulin resistance. Mobilization of fatty acids from this pool is probably regulated by hormone-sensitive lipase (HSL), which has recently been shown to exist in muscle and to be activated by epinephrine via PKA and by contractions via PKC and ERK. 5' AMP-activated protein kinase (AMPK) is an intracellular fuel gauge which regulates metabolism. In this study we incubated rat soleus muscle to investigate if AMPK influences HSL during 5min of repeated tetanic contractions. An eightfold increase in AMPK activity was accompanied by a 2.5-fold increase in phosphorylation of the AMPK-site Ser(565) in HSL (p<0.05). Inhibition of PKC by Calphostin C abolished the contraction-mediated HSL activation while HSL-Ser(565) phosphorylation was not reduced. The study indicates that during contractions AMPK phosphorylates HSL in Ser(565), but this phosphorylation is not directly responsible for the contraction-induced activation of HSL.

AMP-Activated Protein Kinases↗
PubMed2004

Regulation and role of hormone-sensitive lipase in rat skeletal muscle.

Intramyocellular triacylglycerol (TG) is an important energy store, and the energy content of this depot is higher than the energy content of the muscle glycogen depot. It has recently been shown that the mobilization of fatty acids from this TG pool may be regulated by the neutral lipase hormone-sensitive lipase (HSL). This enzyme is known to be rate limiting for intracellular TG hydrolysis in adipose tissue. The presence of HSL has been demonstrated in all muscle fibre types by Western blotting of muscle fibres isolated by collagenase treatment or after freeze-drying. The content of HSL varies between fibre types, being higher in oxidative fibres than in glycolytic fibres. When analysed under conditions optimal for HSL, neutral lipase activity in muscle can be stimulated by adrenaline as well as by contractions. These increases are abolished by the presence of anti-HSL antibody during analysis. Moreover, immunoprecipitation with affinity-purified anti-HSL antibody causes similar reductions in muscle HSL protein concentration and in measured neutral lipase responses to contractions. The immunoreactive HSL in muscle is stimulated by adrenaline via beta-adrenergic activation of cAMP-dependent protein kinase (PKA). From findings in adipocytes it is likely that PKA phosphorylates HSL at residues Ser(563), Ser(659) and Ser(660). Contraction probably also enhances muscle HSL activity by phosphorylation, because the contraction-induced increase in HSL activity is elevated by the protein phosphatase inhibitor okadaic acid and reversed by alkaline phosphatase. A novel signalling pathway in muscle by which HSL activity may be stimulated by protein kinase C (PKC) via extracellular signal-regulated kinase (ERK) has been demonstrated. In contrast to previous findings in adipocytes, in muscle the activation of ERK is not necessary for stimulation of HSL by adrenaline. However, contraction-induced HSL activation is mediated by PKC, at least partly via the ERK pathway. In fat cells ERK is known to phosphorylate HSL at Ser(600). Hence, phosphorylation of different sites may explain the finding that in muscle the effects of contractions and adrenaline on HSL activity are partially additive. In line with the view that the two stimuli act by different mechanisms, training increases contraction-mediated HSL activation but diminishes adrenaline-mediated HSL activation in muscle. In conclusion, HSL is present in skeletal muscle and can be activated by phosphorylation in response to both adrenaline and muscle contractions. Training increases contraction-mediated HSL activation, but decreases adrenaline-mediated HSL activation in muscle.

Animals↗
PubMed2003

Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact.

Lipid metabolism plays an important role in glucose homeostasis under normal and pathological conditions. In adipocytes, skeletal muscle, and pancreatic beta-cells, lipids are mobilized from acylglycerides by the hormone-sensitive lipase (HSL). Here, the consequences of a targeted disruption of the HSL gene for glucose homeostasis were examined. HSL null mice were slightly hyperglycemic in the fasted, but not fed state, which was accompanied by moderate hyperinsulinemia. During glucose challenges, however, disposal of the sugar was not affected in HSL null mice, presumably because of release of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance. Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia.

Adipocytes↗
PubMed2003

Contractions activate hormone-sensitive lipase in rat muscle by protein kinase C and mitogen-activated protein kinase.

Intramuscular triacylglycerol is an important energy store and is also related to insulin resistance. The mobilization of fatty acids from this pool is probably regulated by hormone-sensitive lipase (HSL), which has recently been shown to exist in muscle and to be activated by both adrenaline and contractions. Adrenaline acts via cAMP-dependent protein kinase (PKA). The signalling mediating the effect of contractions is unknown and was explored in this study. Incubated soleus muscles from 70 g male rats were electrically stimulated to perform repeated tetanic contractions for 5 min. The contraction-induced activation of HSL was abolished by the protein kinase C (PKC) inhibitors bisindolylmaleimide I and calphostin C and reduced 50% by the mitogen-activated protein kinase kinase (MEK) inhibitor U0126, which also completely blocked extracellular signal-regulated kinase (ERK) 1 and 2 phosphorylation. None of the inhibitors reduced adrenaline-induced HSL activation in soleus muscle. Both phorbol-12-myristate-13-acetate (PMA), which activates PKC and, in turn, ERK, and caffeine, which increases intracellular Ca2+ without eliciting contraction, increased HSL activity. Activated ERK increased HSL activity in supernatant from basal but not from electrically stimulated muscle. In conclusion, in muscle, PKC can stimulate HSL through ERK. Contractions and adrenaline enhance muscle HSL activity by different signalling mechanisms. The effect of contractions is mediated by PKC, at least partly via the ERK pathway.

Adipocytes↗
PubMed2003

Disruption of microtubules in rat skeletal muscle does not inhibit insulin- or contraction-stimulated glucose transport.

Insulin and muscle contractions stimulate glucose transport in skeletal muscle through a translocation of intracellular GLUT4 glucose transporters to the cell surface. Judged by immunofluorescence microscopy, part of the GLUT4 storage sites is associated with the extensive microtubule cytoskeleton found in all muscle fibers. Here, we test whether microtubules are required mediators of the effect of insulin and contractions. In three different incubated rat muscles with distinct fiber type composition, depolymerization of microtubules with colchicine for < or =8 h did not inhibit insulin- or contraction-stimulated 2-deoxyglucose transport or force production. On the contrary, colchicine at least partially prevented the approximately 30% decrease in insulin-stimulated transport that specifically developed during 8 h of incubation in soleus muscle but not in flexor digitorum brevis or epitrochlearis muscles. In contrast, nocodazole, another microtubule-disrupting drug, rapidly and dose dependently blocked insulin- and contraction-stimulated glucose transport. A similar discrepancy between colchicine and nocodazole was also found in their ability to block glucose transport in muscle giant "ghost" vesicles. This suggests that the ability of insulin and contractions to stimulate glucose transport in muscle does not require an intact microtubule network and that nocodazole inhibits glucose transport independently of its microtubule-disrupting effect.

Animals↗
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↗
PubMed2002

Effect of fiber type and nutritional state on AICAR- and contraction-stimulated glucose transport in rat muscle.

AMP-activated protein kinase (AMPK) may mediate the stimulatory effect of contraction and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on glucose transport in skeletal muscle. In muscles with different fiber type composition from fasted rats, AICAR increased 2-deoxyglucose transport and total AMPK activity approximately twofold in epitrochlearis (EPI), less in flexor digitorum brevis, and not at all in soleus muscles. Contraction increased both transport and AMPK activity more than AICAR did. In EPI muscles, the effects of AICAR and contractions on glucose transport were partially additive despite a lower AMPK activity with AICAR compared with contraction alone. In EPI from fed rats, glucose transport responses were smaller than what was seen in fasted rats, and AICAR did not increase transport despite an increase in AMPK activity. AICAR and contraction activated both alpha(1)- and alpha(2)-isoforms of AMPK. Expression of both isoforms varied with fiber types, and alpha(2) was highly expressed in nuclei. In conclusion, AICAR-stimulated glucose transport varies with muscle fiber type and nutritional state. AMPK is unlikely to be the sole mediator of contraction-stimulated glucose transport.

AMP-Activated Protein Kinases↗
PubMedDate not supplied

Exploring the whereabouts of GLUT4 in skeletal muscle (review).

The glucose transporter GLUT4 is expressed in muscle, fat cells, brain and kidney. In contrast to other glucose transporters, GLUT4 in unstimulated cells is mostly intracellular. Stimuli such as insulin and muscle contractions then cause the translocation of GLUT4 to the cell surface. Questions related to GLUT4 storage compartments, trafficking to the surface membrane, and nature of the intracellular pools, have kept many groups busy for the past 20 years. Yet, one of the main questions in the field remains the universality of GLUT4 features. Can one extrapolate work done on fat cells to muscle or brain? Or vice-versa? Can one use cultures to predict GLUT4 behaviour in fully differentiated tissues? This review summarizes the authors' knowledge of GLUT4 biology in skeletal muscle, which is the predominant tissue for glucose homeostasis. The results are compared to those obtained with the fat cell system, and an attempt is made to assess the universality principle.

Adipocytes↗