Effect of chronic hypoxia on glucose transporters in heart and skeletal muscle of immature and adult rats

Abstract

Glucose transporter (GLUT) modulation can be an important mechanism that contributes to adaptation to hypoxic stress, but little is known about GLUT modulation in heart and skeletal muscle with prolonged hypoxia. In this work, the effect of chronic hypoxia on GLUT-4 and GLUT-1 mRNA and protein was studied in these two tissues in the adult and during development. Hypoxia (fractional inspired O2 = 9 ± 0.5%) was administered to two groups, i.e., an immature group exposed from 3 to 30 days of age and an adult group exposed from 90 to 120 days of age. Rats were then killed and their heart and skeletal muscles were sampled for measurements of GLUT mRNA and protein with Northern and Western blots. In the adult, chronic hypoxia significantly decreased cardiac GLUT mRNA level by >25% of control ( P < 0.05), but had little effect on GLUT protein. A very different hypoxic effect was seen in the immature rat heart with a major increase in protein and no appreciable change in mRNA density. Adult skeletal muscle had no change in GLUT mRNA level but GLUT protein increased (15–20%, P < 0.05) while both GLUT mRNA and protein were significantly increased in the immature skeletal muscles (60–90% over control). We conclude that during chronic O2 deprivation, GLUT-1 and GLUT-4 expressions show a similar pattern but greatly depend on tissue type and age. These differences in GLUT regulation may be due to different strategies for coping with prolonged O2 deprivation in both immature and adult animals.