Decline in muscle insulin-dependent and -independent glucose uptake but not GLUT-4 in 21- vs. 28-day-old rats.

Abstract

The most rapid age-related decrease in insulin-stimulated glucose uptake in skeletal muscle occurs between 3 and 5 wk of age in rats. Therefore, we studied unstimulated, insulin-stimulated, and in vitro hypoxia-stimulated 2-deoxy-D-[G-3H]glucose (2-DG) uptake in isolated soleus, flexor digitorum brevis (FDB), and epitrochlearis muscles from rats at 21, 28, and 35 days of age. Age-related decrements in insulin- (approximately 40-60%) and hypoxia-stimulated (approximately 50%) 2-DG uptake occurred in all muscles, and most of the decline was evident by 28 days. Unstimulated 2-DG uptake declined significantly with advancing age in the epitrochlearis (73%) and FDB (60%) and tended to decrease in the soleus (38%). The time course and relative magnitude of these decrements were similar under unstimulated, insulin-stimulated, and hypoxic conditions. GLUT-4 protein concentration was unaltered by age in each muscle. These results indicate that a substantial age-related decrement in 2-DG uptake occurs in several limb muscles from rats at 21 vs. 28-35 days by a mechanism that is independent of GLUT-4 levels and not specific for the insulin-dependent pathway.