EXPRESSION OF THE GLUCOSE TRANSPORTER GLUT4 IN THE MUSCULAR DYSTROPHIC MDX MOUSE

Glucose transporter protein levels have been investigated in mdx and c ontrol (C57B1/10) mice. Crude membrane fractions (microsomes plus plas ma membranes) were prepared from skeletal muscle, heart, diaphragm and brain of 5-6-week-old and 6-7-month-old control and mdx mice. Using W estern blot analysis with C-terminal-specific anti-peptide antibodies, we investigated the glucose transporters GLUT4 in the different muscl e tissues and GLUT1 in brain. In skeletal tissue from the hindlegs, GL UT4 was increased by approximately 55 % in mdx mice compared with cont rol mice at both ages studied. In the diaphragm, the amount of GLUT4 p rotein was unchanged in young mdx mice, and was decreased by 37.4+/-4. 7 % in older mice compared with age-matched control mice. No differenc e was observed between mdx and control mice in the amounts of GLUT4 an d GLUT1 in heart and brain preparations respectively. To determine whe ther the change in GLUT4 protein observed in the diaphragm and skeleta l muscle of mdx mice was regulated through changes at the level of glu cose transporter mRNA, Northern blot analyses were performed. In skele tal muscle, GLUT4 mRNA level per tissue was not different between the two groups of mice at both ages studied. In contrast, the decrease in the amount of GLUT4 protein observed in the diaphragm of 6-7-month-old mdx mice was accompanied by a decrease in the GLUT4 mRNA level. In co nclusion, the levels of GLUT4 protein were modified in muscle tissues from mdx compared with control mice, and these modifications were diff erent depending on the muscle involved and the age of the mice. An inc rease in the amount of GLUT4 protein in the skeletal muscle of mdx mic e was not due to changes at the mRNA level. The diaphragms of 6-7-mont h-old mdx mice exhibited decreases in GLUT4 protein and mRNA levels th at were not detected in young animals (5-6 weeks old).