Ortmeyer H K, Bodkin N L, Hansen B C
Obesity and Diabetes Research Center, Department of Physiology, School of Medicine, University of Maryland at Baltimore, Baltimore, MD 21201, USA.
Obes Res. 1994 Nov;2(6):549-55. doi: 10.1002/j.1550-8528.1994.tb00104.x.
Chronic caloric restriction (CR) prevents the development of obesity and maintains health, slows aging processes, and prevents or substantially delays the development of non-insulin-dependent diabetes. Because changes in energy metabolism could be involved in all of these positive effects of CR, we examined glycogen synthase (GS) and glycogen phosphorylase (GP) activities and glucose 6-phosphate (G6P) and glycogen concentrations in skeletal muscle samples before and during a euglycemic hyperinsulinemic clamp in 6 older aged monkeys in which CR had been continued for 10.4 +/- 2.1 years. Basal GS activity (fractional velocity and independent) was significantly higher in the CR monkeys than has been previously shown in normal, hyperinsulinemic and diabetic monkeys. The normal effect of insulin to activate GS was absent in the CR group due to the paradoxical finding in some of these monkeys of a reduction in GS activity by insulin. Insulin also had the unexpected effect of increasing the independent activity of GP above basal activity (p<0.05). There was an inverse relationship between the change (insulin-stimulated minus basal) in GS fractional velocity and GP activity ratio (r=-0.91, p<0.005). The basal independent activities of GS and GP were also inversely correlated (r=-0.79, p<0.05). The insulin-stimulated concentration of G6P tended to be higher than the basal concentration (p<0.06) and was significantly higher than that previously shown in normal monkeys (p<0.05). We suggest that long-term calorie restriction (1) results in alterations in glycogen metabolism that may be important to the anti-diabetogenic and antiaging effects of CR and (2) unmasks early defects which may indicate the likelihood of ultimately developing obesity and diabetes.
长期热量限制（CR）可预防肥胖的发生并维持健康，减缓衰老进程，预防或显著延迟非胰岛素依赖型糖尿病的发展。由于能量代谢的变化可能与CR的所有这些积极作用有关，我们检测了6只老年猴子在正常血糖高胰岛素钳夹试验前及试验期间骨骼肌样本中的糖原合酶（GS）和糖原磷酸化酶（GP）活性以及葡萄糖6-磷酸（G6P）和糖原浓度，这些猴子已持续CR 10.4±2.1年。CR猴子的基础GS活性（分数速度和独立活性）显著高于先前在正常、高胰岛素血症和糖尿病猴子中所显示的水平。由于在其中一些猴子中发现胰岛素使GS活性降低这一矛盾现象，CR组中胰岛素激活GS的正常作用消失。胰岛素还产生了意想不到的效果，即使GP的独立活性高于基础活性（p<0.05）。GS分数速度的变化（胰岛素刺激减去基础值）与GP活性比值之间存在负相关（r=-0.91，p<0.005）。GS和GP的基础独立活性也呈负相关（r=-0.79，p<0.05）。胰岛素刺激后的G6P浓度倾向于高于基础浓度（p<0.06），且显著高于先前在正常猴子中所显示的水平（p<0.05）。我们认为，长期热量限制（1）导致糖原代谢改变，这可能对CR的抗糖尿病和抗衰老作用很重要；（2）揭示了早期缺陷，这些缺陷可能表明最终发展为肥胖和糖尿病的可能性。
