GLUT4 translocation and activation of glucose uptake in skeletal muscle can be induced by both physiological (i.e., insulin, nerve stimulation, or exercise) and pharmacological (i.e., phorbol ester) means. Recently, we demonstrated that high glucose levels may mimic the effects of phorbol esters on protein kinase C (PKC) and insulin receptor function (J Biol Chem 269:3381–3386, 1994). In this study, we tested whether the previously described effects of phorbol esters on translocation of GLUT4 in myotubes in culture and also in rat skeletal muscle might be mimicked by glucose. We found that stimulation of C2C12 myotubes with both insulin (10–7) mol/l, 5 min) and glucose (25 mmol/l, 10 min) induces a comparable increase of the GLUT4 content in the plasma membrane. To test whether this effect occurs in intact rat skeletal muscle as well, two different model systems were used. As an in vitro model, isolated rat hindlimbs were perfused for 80 min with medium containing 6 mmol/l glucose ± insulin (1.6 × 10–9 mmol/l, 40 min) or 25 mmol/l glucose. As an in vivo model, acute hyperglycemia (> 11 mmol/l glucose, 20 min) was induced in Wistar rats by intraperitoneal injection of glucose under simultaneous suppression of the endogenous insulin release by injection of somatostatin. In both models, subcellular fractions were prepared from hindlimb skeletal muscle, and plasma membranes were characterized by the enrichment of the marker enzyme α1 Na+ -K+ -ATPase. Acute hyperglaycemia in vivo (n = 5) and in vitro (n = 6) induced an increases of GLUT4 content in the α1 Na+ -K+ -ATPase–enriched fraction (in vivo, 2.45 ± 0.47-fold increase to basal [mean ±SE]; in vitro, 1.71 ± 0.14-fold increase to basal), which was Quantitatively similar to that obtained after insulin treatment (in vivi, 2.35 ± 0.62-fold increase to basal; in vitro, 1.91 ± 0.21-fold increase to basal). Glucose-in-duced GLUT4 translocation in myotubes was prevented by prior addition of the PKC inhibitor 1-(5-isoquinolinyl-by prior addition of the PKC inhibitor 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine; in rat skeletal muscle,GLUT4 translocation was paralleled by a translocation of PKC β, while no effect on PKC α, δ, ∊, and ζ was observed. These results suggest that glucose-induced GLUT4 translocation might represenet an insulin-independent autoregulatory mechanism of the skeletal muscle to rapidly increase glucose uptake in acute hyperglycemia. Activation of PKC β might be involved in this mechanisum in skeletal muscle. GLUT4 translocation was paralleled by a translocation of PKC β, while no effect on PKC α, δ, μ, and ¶ was observed. These results suggest that glucose-induced GLUT4 translocation might represent an insulin-independent autoregulatory mechanism of the skeletal muscle to rapidly increase glucose uptake in acute hyperglycemia. Activation of PKC P might be involved in this mechanism in skeletal muscle.
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Original Articles|
June 01 1995
Acute Hyperglycemia Provides an Insulin-Independent Inducer for GLUT4 Translocation in C2C12 Myotubes and Rat Skeletal Muscle
Paola Galante;
Paola Galante
Institut für Diabetesforschung
Munich, Germany
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Luitgard Mosthaf;
Luitgard Mosthaf
Institut für Diabetesforschung
Munich, Germany
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Monika Kellerer;
Monika Kellerer
Institut für Diabetesforschung
Munich, Germany
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Lucia Berti;
Lucia Berti
Institut für Diabetesforschung
Munich, Germany
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Stefanie Tippmer;
Stefanie Tippmer
Institut für Diabetesforschung
Munich, Germany
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Birgit Bossenmaier;
Birgit Bossenmaier
Institut für Diabetesforschung
Munich, Germany
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Toshihiko Fujiwara;
Toshihiko Fujiwara
Sankyo Company Limited Pharmacology and Molecular Biology Laboratories
Tokyo, Japan
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Akira Okuno;
Akira Okuno
Sankyo Company Limited Pharmacology and Molecular Biology Laboratories
Tokyo, Japan
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Hiroyoshi Horikoshi;
Hiroyoshi Horikoshi
Sankyo Company Limited Pharmacology and Molecular Biology Laboratories
Tokyo, Japan
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Hans Ulrich Häring
Hans Ulrich Häring
Institut für Diabetesforschung
Munich, Germany
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Address correspondence and reprint requests to Prof. Hans U. Häring, Institut für Diabetesforschung, Kölner PI. 1, 80804 Munich, Germany.
Diabetes 1995;44(6):646–651
Article history
Received:
July 18 1994
Revision Received:
January 04 1995
Accepted:
January 04 1995
PubMed:
7789629
Citation
Paola Galante, Luitgard Mosthaf, Monika Kellerer, Lucia Berti, Stefanie Tippmer, Birgit Bossenmaier, Toshihiko Fujiwara, Akira Okuno, Hiroyoshi Horikoshi, Hans Ulrich Häring; Acute Hyperglycemia Provides an Insulin-Independent Inducer for GLUT4 Translocation in C2C12 Myotubes and Rat Skeletal Muscle. Diabetes 1 June 1995; 44 (6): 646–651. https://doi.org/10.2337/diab.44.6.646
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