EFFECT OF CHRONIC HYPOXIA ON GLUCOSE TRANSPORTERS IN HEART AND SKELETAL-MUSCLE OF IMMATURE AND ADULT RATS

Glucose transporter (GLUT) modulation can be an important mechanism th at contributes to adaptation to hypoxic stress, but little is known ab out GLUT modulation in heart and skeletal muscle with prolonged hypoxi a. In this work, the effect of chronic hypoxia on GLUT-4 and GLUT-1 mR NA and protein was studied in these two tissues in the adult and durin g development. Hypoxia (fractional inspired O-2 = 9 +/- 0.5%) was admi nistered to two groups, i.e., an immature group exposed hom 3 to 30 da ys 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 m RNA 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 m RNA density: Adult skeletal muscle had no change in GLUT mRNA level bu t GLUT protein increased (15-20%, P < 0.05) while both GLUT mRNA and p rotein were significantly increased in the immature skeletal muscles ( 60-90% over control). We conclude that during chronic O-2 deprivation, GLUT-1 and GLUT-4 expressions show a similar pattern but greatly depe nd on tissue type and age. These differences in GLUT regulation may be due to different strategies for coping with prolonged O-2 deprivation in both immature and adult animals.