Kinetics of Native Insulin in Diabetic, Obese, and Aged Men
Kinetics of Native Insulin in Diabetic, Obese, and Aged Men
复制标题
糖尿病、肥胖和老年男性中天然胰岛素的动力学
作者：
E. A. McGuire;J. Tobin;M. Berman;R. Andres
使用正常血糖钳夹技术，在 69 名年龄为 18-83 岁、肥胖指数为 0.93-1.51 的非糖尿病男性受试者和 12 名年龄为 46-78 岁、肥胖指数为 0.95-1.56 的成年发病糖尿病患者中研究了未标记猪胰岛素的动力学。通过使用数学模型对胰岛素动力学数据进行分析，可以确定每个个体的稳态分布质量和降解速率常数。对个体进行分组，以便根据年龄、肥胖指数或糖尿病对结果进行比较。在 120 毫米的时间内，对胰岛素输注和清除的反应显示出一些随年龄、肥胖或糖尿病而出现的短暂和稳态差异。通过使用房室模型对这些数据进行分析得出的结论是，在稳定状态下，与适当的对照相比，血管外空间中的胰岛素与血浆中的胰岛素的比率（T/P）在中度肥胖组（26%）和糖尿病组（17%）中降低，但在老年组（13%）中升高。由于血管外胰岛素包括与受体结合的胰岛素和间质液中的胰岛素，因此观察到的血管外与血浆质量比的变化很可能反映了体内与受体结合的变化，尽管变化的幅度会因间质空间相对于血浆的大小的变化而有所改变。此外，新胰岛素进入血浆的比率（BSDR）在糖尿病人群（45%；P <0.02）以及中度肥胖组（27%）中增加，但在老年组（11%）中有所下降。从结果中可以得出以下一般性结论： 肥胖症的参数变化模式与成年期发病的糖尿病相似。肥胖和成年发病糖尿病导致的 T/P 下降不能仅用这些人群空腹血浆胰岛素水平的变化来解释。在老年受试者中观察到的变化模式与在成熟期发病的糖尿病患者中观察到的变化模式相反，这表明糖尿病是一种不同于正常衰老过程的扰动。最后，胰岛素代谢的变化并不大，因此它们不太可能是衰老、肥胖或糖尿病引起的葡萄糖耐量主要变化的唯一原因。
The kinetics of unlabeled porcine insulin were studied in 69 nondiabetic male subjects aged 18–83 yr with obesity indexes of 0.93–1.51 and in 12 maturity-onset diabetics age 46–78 yr with obesity indexes of 0.95–1.56 by using the euglycemic clamp technique. Analysis of the insulin kinetic data by using a mathematical model permitted the determination, for each individual, of steady state distribution masses and degradation rate constants. The individuals were grouped to allow comparison of the results on the basis of age, obesity index, or diabetes. The responses over a period of 120 mm to an infusion and wash out of insulin show some transient as well as steady state differences with age, obesity, or diabetes. Analysis of these data by use of compartmental models leads to the conclusion that in the steady state the ratio of insulin in extravascular spaces to that in plasma (T/P) is decreased in the moderately obese group (26%) and in the diabetic group (17%) but increased in the older group (13%) when each is compared with the appropriate control. Since extravascular insulin includes both insulin bound to receptors and insulin in the interstitial fluid, the observed changes in the extravascular to plasma mass ratio most likely reflect changes in in vivo binding to receptors, although the magnitude of the change would be modified somewhat by changes in the size of the interstitial spaces relative to plasma. In addition, the rate of entry of new insulin into plasma (BSDR) was increased in the diabetic population (45%; P <0.02) as well as in the moderately obese group (27%) but was decreased somewhat in the older group (11%). The following general conclusions can be drawn from the results: The pattern of parameter changes seen with obesity is similar to that seen with maturity-onset diabetes. The decrease in T/P seen with obesity and with maturity-onset diabetes cannot be accounted for solely by changes in fasting plasma insulin levels in these populations. The pattern of changes seen in the older subjects is opposite that seen in the maturity-onset diabetics, which suggests that diabetes is a perturbation distinct from the normal aging process. Finally, the changes in the metabolism of insulin are not large, making it unlikely that they are the sole cause of the major alterations in glucose tolerance seen with aging, obesity, or diabetes.