Kahn S E, Larson V G, Schwartz R S, Beard J C, Cain K C, Fellingham G W, Stratton J R, Cerqueira M D, Abrass I B
Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle.
J Clin Endocrinol Metab. 1992 Jun;74(6):1336-42. doi: 10.1210/jcem.74.6.1592879.
Aging has been associated with glucose intolerance, insulin resistance, hyperinsulinemia, and diminished islet B-cell function. The relative contribution of these factors to the aging-associated changes in glucose tolerance has been difficult to discern, particularly so for B-cell function, since insulin sensitivity itself is a determinant of B-cell function and, therefore, comparisons of insulin levels and responses between old and young subjects are difficult. To reduce this effect, we compared B-cell function in 14 healthy older men (aged 61-82 yr; body mass index, 21-30 kg/m2), who were exercise trained for 6 months to improve insulin sensitivity, to that of 11 healthy young men (aged 24-31 yr; body mass index, 19-31 kg/m2), who were also trained. Insulin-glucose interactions were assessed by measuring indices of insulin sensitivity (SI) and glucose effectiveness at zero insulin (GEZI) using Bergman's minimal model. B-Cell function was assessed by determining the acute insulin responses (AIR) to glucose (AIRgluc) and arginine at 3 different glucose levels: fasting, approximately 14 mM, and greater than 28 mM (AIRmax). AIRmax provides a measure of B-cell secretory capacity, while the glucose level at which 50% of AIRmax occurs is termed PG50 and is used to estimate B-cell sensitivity to glucose. The insulin sensitivity and glucose effectiveness at zero insulin of the trained older subjects was similar to that of the trained young [SI: old, 5.1 +/- 0.6; young, 6.5 +/- 0.7 x 10(-5) min-1/pM (mean +/- SEM; P = NS); GEZI: old, 1.3 +/- 0.2; young, 1.7 +/- 0.2 x 10(-2) min (P = NS)]. Under these conditions, the fasting glucose levels (old, 5.4 +/- 0.2; young, 5.1 +/- 0.1 mM) and basal insulin levels (old, 49 +/- 6; young, 63 +/- 11 pM) were also similar in the two groups. AIRgluc values were lower in the exercised elderly (old, 253 +/- 50; young, 543 +/- 101 pM; P = 0.01). This decrease in stimulated insulin release was due solely to a reduction in the AIRmax (old, 1277 +/- 179; young, 2321 +/- 225 pM; P less than 0.005); the PG50 was not different (old, 8.9 +/- 0.4; young, 8.8 +/- 0.2 mM; P = NS). These differences in the older subjects were associated with a reduction in iv glucose tolerance (old, 1.49 +/- 0.15; young, 1.95 +/- 0.13%/min; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
衰老与葡萄糖耐量异常、胰岛素抵抗、高胰岛素血症以及胰岛B细胞功能减退有关。这些因素对衰老相关的葡萄糖耐量变化的相对贡献难以区分，特别是对于B细胞功能而言，因为胰岛素敏感性本身就是B细胞功能的一个决定因素，因此，很难比较老年和年轻受试者之间的胰岛素水平和反应。为了减少这种影响，我们将14名健康老年男性（年龄61 - 82岁；体重指数，21 - 30 kg/m²）的B细胞功能与11名健康年轻男性（年龄24 - 31岁；体重指数，19 - 31 kg/m²）的B细胞功能进行了比较，这两组男性都接受了为期6个月的运动训练以提高胰岛素敏感性。使用伯格曼最小模型，通过测量胰岛素敏感性指数（SI）和零胰岛素时的葡萄糖效能（GEZI）来评估胰岛素 - 葡萄糖相互作用。通过测定在3种不同葡萄糖水平（空腹、约14 mM和大于28 mM）下对葡萄糖（AIRgluc）和精氨酸的急性胰岛素反应（AIR）来评估B细胞功能：AIRmax。AIRmax提供了B细胞分泌能力的一种度量，而发生50% AIRmax时的葡萄糖水平称为PG50，用于估计B细胞对葡萄糖的敏感性。经过训练的老年受试者的胰岛素敏感性和零胰岛素时的葡萄糖效能与经过训练的年轻受试者相似[SI：老年，5.1±0.6；年轻，6.5±0.7×10⁻⁵ min⁻¹/pM（均值±标准误；P =无显著性差异）；GEZI：老年，1.3±0.2；年轻，1.7±0.2×10⁻² min（P =无显著性差异）]。在这些条件下，两组的空腹血糖水平（老年，5.4±0.2；年轻，5.1±0.1 mM）和基础胰岛素水平（老年，49±6；年轻，63±11 pM）也相似。运动后的老年人的AIRgluc值较低（老年，253±50；年轻，543±101 pM；P = 0.01）。刺激后胰岛素释放的这种降低完全是由于AIRmax的降低（老年，1277±179；年轻，2321±225 pM；P＜0.005）；PG50没有差异（老年，8.9±0.4；年轻，8.8±0.2 mM；P =无显著性差异）。老年受试者的这些差异与静脉注射葡萄糖耐量的降低有关（老年，1.49±0.15；年轻，1.95±0.13%/min；P＜0.05）。（摘要截于400字）
