Muscle-specific transgenic complementation of GLUT4-deficient mice. Effects on glucose but not lipid metabolism.
We have taken the approach of introducing the muscle-specific myosin light chain (MLC)-GLUT4 transgene into the GLUT4-null background to assess the relative role of muscle and adipose tissue GLUT4 in the etiology of the GLUT4-null phenotype. The resulting MLC-GLUT4-null mice express GLUT4 predominantly in the fast-twitch extensor digitorum longus (EDL) muscle. GLUT4 is nearly absent in female white adipose tissue (WAT) and slow-twitch soleus muscle of both sexes of MLC-GLUT4-null mice. GLUT4 content in male MLC-GLUT4-null WAT is 20% of that in control mice. In transgenically complemented EDL muscle, 2-deoxyglucose (2-DOG) uptake was restored to normal (male) or above normal (female) levels. In contrast, 2-DOG uptake in slow-twitch soleus muscle of MLC-GLUT4-null mice was not normalized. With the normalization of glucose uptake in fast-twitch skeletal muscle, whole body insulin action was restored in MLC-GLUT4-null mice, as shown by the results of the insulin tolerance test. These results demonstrate that skeletal muscle GLUT4 is a major regulator of skeletal muscle and whole body glucose metabolism. Despite normal skeletal muscle glucose uptake and insulin action, the MLC-GLUT4-null mice exhibited decreased adipose tissue deposits, adipocyte size, and fed plasma FFA levels that are characteristic of GLUT4-null mice. Together these results indicate that the defects in skeletal muscle and whole body glucose metabolism and adipose tissue in GLUT4-null mice arise independently.
Tsao
T S
TS
Department of Biochemistry, Albert Einstein College of Medicine, New York 10461, USA.
Stenbit
A E
AE
Li
J
J
Houseknecht
K L
KL
Zierath
J R
JR
Katz
E B
EB
Charron
M J
MJ
D000818:Animals; D005260:Female; D018014:Gene Transfer Techniques; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D018994:Myosin Light Chains / Q000235:genetics; D011401:Promoter Regions, Genetic
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D018994:Myosin Light Chains; C495693:Slc2a4 protein, mouse; D005947:Glucose