Insulin-induced translocation of GLUT 4 in skeletal muscle of insulin-resistant Zucker rats.
The genetically obese Zucker rat (fa/fa) is an animal model with severe insulin resistance of the skeletal muscle. We investigated whether a defect of insulin-dependent glucose transporter (GLUT 4) translocation might contribute to the pathogenesis of the insulin-resistant state. fa/fa rats, lean controls (Fa/Fa) as well as normal Wistar rats were injected intraperitoneally with insulin and were killed after 2 or 20 min, respectively. Subcellular fractions were prepared from hind-limb skeletal muscle and were characterized by determination of marker-enzyme activities and immunoblotting applying antibodies against alpha 1 Na+/K+ ATPase. The relative amounts of GLUT 1 and GLUT 4 were determined in the fractions by immunoblotting with the respective antibodies. Insulin induced an approximately two-fold increase of GLUT 4 in a plasma membrane and transverse tubule enriched fraction and a decrease in the low density enriched membrane fraction in all three groups of rats. There was a high individual variation in GLUT 4 translocation efficiency within the groups. However, no statistically significant difference was noted between the groups. No effect of insulin was detectable on the distribution of GLUT 1 or alpha 1 Na+K+ ATPase. The data suggest that skeletal muscle insulin resistance of obese Zucker rats is not associated with a lack of GLUT 4 translocation.
Galante
P
P
Institute for Diabetes Research, Munich, Germany.
Maerker
E
E
Scholz
R
R
Rett
K
K
Herberg
L
L
Mosthaf
L
L
Häring
H U
HU
D000818:Animals; D000906:Antibodies; D002462:Cell Membrane / Q000378:metabolism; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000235:genetics*; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000096:biosynthesis*; D009124:Muscle Proteins; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase