Intracellular pathways of insulin-mediated glucose uptake before and after puberty in conscious rats

Studies in humans and animals indicate that peripheral insulin sensitivity is decreased after puberty. Although glucose, after its uptake and phosphorylation, will be diverted to either the glycolytic or glycogen synthesis pathway, these pathways have not been characterized after the transition to puberty. Thus, we examined the changes in the pathways of glucose utilization in conscious (n = 22) prepuberty (81 +/- 3 g), and postpuberty (258 +/- 9 g) Sprague-Dawley rats. Insulin stimulated (by insulin clamp 18 mU/kg/min) glucose uptake [rate of glucose disappearance (Rd)] was decreased by approximately 30% postpuberty (from 339 +/- 22 to 239 +/- 28 mumol/kg/min; p < 0.001). Although glycolysis (estimated by the rate of conversion of [3H]glucose to 3H2O) decreased by approximately 15% (p < 0.05), glycogen synthesis decreased by approximately 40% (from 200 +/- 17 prepuberty to 122 +/- 22 mumol/kg/min postpuberty; p < 0.001), and accounted for approximately 80% of the decrease in Rd postpuberty. Decrease in the capacity to store glycogen in response to insulin was also confirmed by approximately 40% decrease in both glycogen levels, and in 3H accumulation into glycogen (from 3H-glucose) at the end of the clamp study. This occurred in the absence of any changes in either the K(m) or the Vmax of glycogen synthase nor in the activity of glycogen phosphorylase. We conclude that the postpubertal decrease in insulin responsiveness is characterized by decreased ability to store muscle glycogen. We propose that high capacity for muscle glycogen synthesis may be required to sustain the increased metabolic requirements during peripubertal growth.