INTRACELLULAR PATHWAYS OF INSULIN-MEDIATED GLUCOSE-UPTAKE BEFORE AND AFTER PUBERTY IN CONSCIOUS RATS

Studies in humans and animals indicate that peripheral insulin sensiti vity is decreased after puberty, Although glucose, after its uptake an d phosphorylation, will be diverted to either the glycolytic or glycog en synthesis pathway, these pathways have not been characterized after the transition to puberty, Thus, we examined the changes in the pathw ays of glucose utilization in conscious (n = 22) prepuberty (81 +/- 3 g), and postpuberty (258 +/- 9 g) Sprague-Dawley rats. Insulin stimula ted (by insulin clamp 18 mU/kg/min) glucose uptake [rate of glucose di sappearance (R(d))] was decreased by similar to 30% postpuberty (from 339 +/- 22 to 239 +/- 28 mu mol/kg/min; p < 0.001). Although glycolysi s (estimated by the rate of conversion of [H-3]glucose to (H2O)-H-3) d ecreased by similar to 15% (p < 0.05), glycogen synthesis decreased by similar to 40% (from 200 +/- 17 prepuberty to 122 +/- 22 mu mol/kg/mi n postpuberty; p < 0.001), and accounted for similar to 80% of the dec rease in R(d) postpuberty, Decrease in the capacity to store glycogen in response to insulin was also confirmed by similar to 40% decrease i n both glycogen levels, and in H-3 accumulation into glycogen (from H- 3-glucose) at the end of the clamp study. This occurred in the absence of any changes in either the K-m or the V-max of glycogen synthase no r in the activity of glycogen phosphorylase, We conclude that the post pubertal decrease in insulin responsiveness is characterized by decrea sed ability to store muscle glycogen. We propose that high capacity fo r muscle glycogen synthesis may be required to sustain the increased m etabolic requirements during peripubertal growth.