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

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(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.