Insulin Induces the Translocation of GLUT4 From a Unique Intracellular Organelle to Transverse Tubules in Rat Skeletal Muscle

Marette, André; Burdett, Elena; Douen, Andre G.; Vranić, Mladen; Klip, Amira

doi:10.2337/diab.41.12.1562

Cited by 139 publications

(116 citation statements)

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“…In addition, the PKC isoform z previously shown to be activated by insulin was not changed providing further support for the inhibition of the early steps of insulin signalling cascade [32]. Noteworthy, in contrast to an insulin-dependent GLUT4 translocation [12,13,14], we observed no translocation of GLUT4 to Table 5. Quantification of the effect of glucose infusion on PKC isoforms translocation.…”

Section: Discussionsupporting

confidence: 73%

Prolonged glucose infusion into conscious rats inhibits early steps in insulin signalling and induces translocation of GLUT4 and protein kinase C in skeletal muscle

et al. 2002

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Impairment of the glucose transport in the insulinsensitive tissues contributes to the pathogenesis of Type II (non-insulin-dependent) diabetes mellitus [1,2]. Skeletal muscle represents the most important tissue for the maintenance of a balanced postprandial glucose homeostasis; about 80 % of insulin-stimulated glucose uptake is accounted for by muscle [3±5]. The influx of glucose into muscle is mediated by the glucose transporter proteins GLUT1 and the insulinsensitive GLUT4 [6±11]. Insulin induces the translocation of GLUT4 to the sarcolemma and to special- Abstract Aims/hypothesis. Previous studies on diabetic patients have shown that hyperglycaemia increases glucose uptake in an apparently insulin-independent manner. However, the molecular mechanism has not been clarified. Methods. We studied rats receiving continuous glucose infusion to address this question. In this animal model, rats accommodate systemic glucose oversupply and rapidly develop insulin resistance. Results. Glucose infusion increased both plasma glucose and insulin concentrations to peak after one day. In spite of continuous glucose infusion normoglycaemia was reached after 5 days while insulin concentrations remained higher. Focusing our studies in day 2 (hyperglycaemia/hyperinsulinaemia) and day 5 (normoglycaemia/hyperinsulinaemia) we found, particularly in day 5, that the early steps of the insulin signalling cascade in skeletal muscle of glucose-infused rats were not more activated when compared to control animals as assessed by a comparable phosphorylation of the insulin receptor, IRS-1 and PKB and by an unaltered IRS-1-associated Ptd(Ins) 3' kinase activity. Continuous glucose infusion induced GLUT4 protein expression and translocation to the plasma membrane while neither expression nor translocation of GLUT1 was affected. Translocation of PKC-bI, -bII (> threefold) and -a, -q (to a lesser extent) to the plasma membrane was significantly induced after 2 days but not after 5 days of glucose infusion when normoglycaemia was reached. Conclusions/interpretation. Our data support the hypothesis that continuous glucose infusion induces translocation of GLUT4 while the early steps of the insulin signalling cascade were not increased. These effects could be mediated by activation of PKC. [Diabetologia (2002) 45: 356±368]

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Section: Discussionsupporting

confidence: 73%

Prolonged glucose infusion into conscious rats inhibits early steps in insulin signalling and induces translocation of GLUT4 and protein kinase C in skeletal muscle

et al. 2002

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“…For example, immunoelectron microscopy has demonstrated the predominant localization of GLUT4 protein (∼60%) in tubulo-vesicular elements beneath the plasma membrane with the remaining protein localized to the trans-Golgi network (TGN), clathrin-coated vesicles and to endosome structures. [18][19][20][21]. The content of GLUT4 in all these compartments was found to decrease in response to insulin concomitant with an increased distribution to the plasma membrane.…”

Section: Glut4 Intracellular Retention and Exocytosismentioning

confidence: 88%

“…In part this is because at steady-state GLUT4 is distributed at varying levels throughout most of the endomembrane system [17][18][19][20][21]. Indeed, following insulin-stimulated translocation, GLUT4 is retrieved from the plasma membrane by endocytosis and routed through a complex trafficking itinerary that appears to include endosome compartments and perhaps the trans-Golgi network, before returning to the IRC.…”

Section: Glut4 Intracellular Retention and Exocytosismentioning

confidence: 99%

Ins (endocytosis) and outs (exocytosis) of GLUT4 trafficking

Hou

Pessin

2007

Current Opinion in Cell Biology

132

116

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SummaryGlucose transporter 4 (GLUT4) is the major insulin regulated glucose transporter expressed mainly in muscle and adipose tissue. GLUT4 is stored in a poorly characterized intracellular vesicular compartment and translocates to the cell surface in response to insulin stimulation resulting in increase glucose uptake. This process is essential for the maintenance of normal glucose homeostasis and involves a complex interplay of trafficking events and intracellular signaling cascades. Recent studies have identified sortilin as an essential element for the formation of GLUT4 storage vesicles during adipogenesis and GGA (Golgi-localized γ-ear-containing Arf-binding protein) as a key coat adaptor for the entry of newly synthesized GLUT4 into the specialized compartment. Insulinstimulated GLUT4 translocation from this compartment to the plasma membrane appears to require the Akt/protein kinase B substrate, termed AS160 (Akt Substrate of 160 kDa). In addition, the VPS9 domain-containing protein Gapex-5 in complex with CIP4 appears to function as a Rab31 guanylnucleotide exchange factor that is necessary for insulin-stimulated GLUT4 translocation. Here we attempt to summaries recent advances in GLUT4 vesicle biogenesis, intracellular trafficking and membrane fusion.

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“…Skeletal muscle expresses both the GLUT1 and GLUT4 glucose transporters but it is the mobilization of GLUT4, from an intracellular store to the plasma membrane (PM), that explains the observed increase in glucose transport in response to insulin binding [5][6][7][8]. In contrast, GLUT1 expression is largely restricted to the PM where, under normal *Corresponding author.…”

Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

“…Little is known regarding the nature and identity of the intracellular compartments containing the GLUT4 transporter and the subunits of the Na,K-ATPase. However, subcellular fractionation studies have revealed that the insulin-induced loss of both GLUT4 and the ~2-Na,K-ATPase subunit occurs from intracellular membranes (IM) of the same buoyant density [7,12]. This observation may signify that these proteins are colocalized in a single intracellular pool enabling them to be recruited to the PM simultaneously upon insulin stimulation.…”

mentioning

confidence: 99%

Sedimentation and immunological analyses of GLUT4 and α2‐Na,K‐ATPase subunit‐containing vesicles from rat skeletal muscle: evidence for segregation

Aledo

Hundal

1995

FEBS Letters

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In skeletal muscle insulin induces the translocation of both the GLUT4 glucose transporter and the 62 subunit of the Na,K-ATPase from an intraceHnlar membrane (154) compartment to the plasma membrane (PM). Fractionation studies of rat skeletal muscle using a discontinuous sucrose gradient have indicated that the insulin-induced loss of both proteins occurs from a fraction containing intracellular membranes (IM) of common density. This raises the possibility that both proteins may be colocalized in a single intracellular compartment or are present in separate membrane vesicles that are of similar buoyant density. In this study we report that membrane vesicles from the insulinresponsive IM fraction can in fact be separated on the basis of differences in their sedimentation velocities; immunoblot analyses of fractions collected from a sucrose velocity gradient revealed the presence of two separate peaks for GLUT4 and the a2 subunit of the Na,K-ATPase. One of these peaks representing a fast sedimenting population of vesicles (with a sedimentation coefficient of 2697 + 57 S) reacted against antibodies to the 62 subunit of the Na,K-ATPase, whereas, the second peak contained a population of much slower sedimenting vesicles (with a sedimentation coefficient of 209 -+ 4 S) were practically devoid of the a2-subunit. By contrast, the slow sedimenting vesicles were enriched by ~32-fold in GLUT4 relative to the starting IM fraction when the fractional protein content was taken into account. Immunoprecipitation of GLUT4-containing vesicles from the insulin-sensitive IM fraction revealed that no immunoreactivity towards either the a2 or the ~1 subunits of the Na,K-ATPase could be observed, signifying that the insulin-responsive subunits of the Na,K-ATPase and GLUT4 were present in different membrane vesicles and that it was unlikely, therefore, that the insulin-induced redistribution of these proteins to the PM occurs from a common intracellular pool.

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Insulin Induces the Translocation of GLUT4 From a Unique Intracellular Organelle to Transverse Tubules in Rat Skeletal Muscle

Cited by 139 publications

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Prolonged glucose infusion into conscious rats inhibits early steps in insulin signalling and induces translocation of GLUT4 and protein kinase C in skeletal muscle

Prolonged glucose infusion into conscious rats inhibits early steps in insulin signalling and induces translocation of GLUT4 and protein kinase C in skeletal muscle

Ins (endocytosis) and outs (exocytosis) of GLUT4 trafficking

Sedimentation and immunological analyses of GLUT4 and α2‐Na,K‐ATPase subunit‐containing vesicles from rat skeletal muscle: evidence for segregation

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