Acute hyperglycemia provides an insulin-independent inducer for GLUT4 translocation in C2C12 myotubes and rat skeletal muscle

• Published in: Diabetes (New York, N.Y.) Vol. 44; no. 6; pp. 646 - 651
• Main Authors: Galante, P., Mosthaf, L., Kellerer, M., Berti, L., Tippmer, S., Bossenmaier, B., Fujiwara, T., Okuno, A., Horikoshi, H., Haring, H. U.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01-06-1995
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.44.6.646

Acute hyperglycemia provides an insulin-independent inducer for GLUT4 translocation in C2C12 myotubes and rat skeletal muscle.
P Galante ,
L Mosthaf ,
M Kellerer ,
L Berti ,
S Tippmer ,
B Bossenmaier ,
T Fujiwara ,
A Okuno ,
H Horikoshi and
H U Häring
Institut für Diabetesforschung, Munich, Germany.
Abstract
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 x 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 alpha 1 Na(+)-K(+)-ATPase.