Raghavan S, Saenger P, Hu M, Barzilai N
Division of Adult Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Pediatr Res. 1997 Mar;41(3):340-5. doi: 10.1203/00006450-199703000-00006.
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.
对人类和动物的研究表明，青春期后外周胰岛素敏感性会降低。尽管葡萄糖在摄取和磷酸化后会被导向糖酵解或糖原合成途径，但在进入青春期后，这些途径尚未得到明确表征。因此，我们研究了清醒状态下（n = 22）青春期前（81 ± 3 g）和青春期后（258 ± 9 g）的斯普拉格-道利大鼠葡萄糖利用途径的变化。胰岛素刺激（通过胰岛素钳夹，18 mU/kg/min）的葡萄糖摄取[葡萄糖消失率（Rd）]在青春期后降低了约30%（从339 ± 22降至239 ± 28 μmol/kg/min；p < 0.001）。尽管糖酵解（通过[3H]葡萄糖转化为3H2O的速率估算）降低了约15%（p < 0.05），但糖原合成降低了约40%（从青春期前的200 ± 17降至青春期后的122 ± 22 μmol/kg/min；p < 0.001），并且占青春期后Rd降低的约80%。在钳夹研究结束时，糖原水平和3H（来自3H-葡萄糖）积累到糖原中的量均降低了约40%，这也证实了胰岛素刺激下糖原储存能力的下降。这一现象发生时，糖原合酶的米氏常数（K(m)）或最大反应速度（Vmax）以及糖原磷酸化酶的活性均未发生任何变化。我们得出结论，青春期后胰岛素反应性的降低表现为肌肉糖原储存能力的下降。我们提出，可能需要较高的肌肉糖原合成能力来维持青春期前后生长期间增加的代谢需求。
