Expression of the glucose transporter GLUT4 in the muscular dystrophic mdx mouse

Abstract

Glucose transporter protein levels have been investigated in mdx and control (C57Bl/10) mice. Crude membrane fractions (microsomes plus plasma 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 Western blot analysis with C-terminal-specific anti-peptide antibodies, we investigated the glucose transporters GLUT4 in the different muscle tissues and GLUT1 in brain. In skeletal tissue from the hindlegs, GLUT4 was increased by approximately 55% in mdx mice compared with control mice at both ages studied. In the diaphragm, the amount of GLUT4 protein was unchanged in young mdx mice, and was decreased by 37.4 +/- 4.7% in older mice compared with age-matched control mice. No difference was observed between mdx and control mice in the amounts of GLUT4 and GLUT1 in heart and brain preparations respectively. To determine whether the change in GLUT4 protein observed in the diaphragm and skeletal muscle of mdx mice was regulated through changes at the level of glucose transporter mRNA, Northern blot analyses were performed. In skeletal 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 conclusion, the levels of GLUT4 protein were modified in muscle tissues from mdx compared with control mice, and these modifications were different depending on the muscle involved and the age of the mice. An increase in the amount of GLUT4 protein in the skeletal muscle of mdx mice was not due to changes at the mRNA level. The diaphragms of 6-7-month-old mdx mice exhibited decreases in GLUT4 protein and mRNA levels that were not detected in young animals (5-6 weeks old).