Comprehensive analysis of glucose metabolism by using stable-labeled minimal model approach

(1)本文分析了32例葡萄糖耐量正常受试者、15例空腹血糖受损和/或糖耐量受损受试者和11例糖尿病受试者（空腹血糖< 126 mg/dl）静脉葡萄糖耐量试验（IVGTT）中葡萄糖消失的决定因素。IVGTT中的葡萄糖耐量（Kg值）和激发后葡萄糖水平（口服激发）主要由对葡萄糖的急性胰岛素反应（AIR）和外周组织特异性胰岛素敏感性（SI 2 *）确定。因此，在AIR较低的受试者中，SI 2 * 降低将导致Kg值和攻毒后血糖水平恶化。相比之下，空腹血糖水平主要由肝脏胰岛素敏感性和非胰岛素依赖性（葡萄糖依赖性）组织葡萄糖摄取（Sg 2 *，葡萄糖有效性）以及AIR决定。(2)运动训练对外周组织特异性胰岛素敏感性（SI 2 *）和葡萄糖有效性（SG 2 *）的影响在健康受试者中，12周的运动训练和单次30分钟的运动都会增加SI 2 * 和SG 2 *（参考文献1和2）。(3)未来的方向我们现在已经通过使用新的最小模型分析（包括另一种肝脏成分）构建了新的肝脏胰岛素敏感性（hSI 2）和肝脏葡萄糖有效性（hSG 2）指数（Am J Physiol 288：E1038，2005）。利用这些新的指标，目前正在进一步分析糖耐量异常的发病机制和运动训练的影响。

(1) Pathogenesis of glucose intolerance in Japanese populationDeterminants of glucose disappearance in intravenous glucose tolerance tests (IVGTT) is analyzed in 32 subjects with normal glucose tolerance, 15 subjects with impaired fasting glucose and/or impaired glucose tolerance, and 11 subjects with diabetes mellitus (fasting glucose < 126 mg/dl). Glucose tolerance in IVGTT (Kg values) and post-challenge glucose levels (oral challenge) are mainly determined by acute insulin response (AIR) to glucose and peripheral-tissue specific insulin sensitivity (SI2*). Therefore, in subjects with lower AIR, decrease in SI2* would result in deterioration in Kg values and post-challenge glucose levels. In contrast, fasting glucose levels are mainly determined by hepatic insulin sensitivity and non-insulin-dependent (glucose-dependent) tissue glucose uptake (Sg2*, glucose effectiveness), in addition to AIR.(2) Effects of exercise training on peripheral-tissue specific insulin sensitivity (SI2*) and glucose effectiveness (SG2*)In healthy subjects, both 12 weeks of exercise training and a single bout of 30 minute exercise increase SI2* and SG2* (Reference 1 & 2).(3) Future directionsWe have now constructed new indices of hepatic insulin sensitivity (hSI2) and hepatic glucose effectiveness (hSG2) by using new minimal model analysis including another hepatic component (Am J Physiol 288: E1038, 2005). Using these new indices, further analysis is now being made on pathogenesis of glucose intolerance and effects of exercise training.