Effects of exercise on hepatic insulin sensitivity.

作为体内内源性葡萄糖产生的主要来源，肝脏在葡萄糖稳态中起着至关重要的作用。尽管肝脏和胰岛素在维持正常葡萄糖稳态中的重要性，但关于肝脏胰岛素敏感性的文献很少。本研究的目的是：1）建立一种新的静脉葡萄糖耐量试验检测肝脏胰岛素敏感性的方法。2)以评估体内肝脏葡萄糖产生。3)评价运动对葡萄糖代谢包括肝脏葡萄糖生成和肝脏胰岛素敏感性的影响。1）肝脏和外周葡萄糖调节综合模型评估肝脏胰岛素敏感性。肝脏和外周葡萄糖代谢的综合模型描述了标记葡萄糖耐量试验期间的外源性和内源性葡萄糖动力学。该模型还提供了内源性葡萄糖产生的参数描述。本研究通过将肝脏胰岛素敏感性定义为胰岛素增强内源性葡萄糖产生的葡萄糖抑制的能力（提交给Computer Method & Programs in Biomedicine 2007）来扩展模型的理论潜力。2）使用稳定同位素，可以估计内源性葡萄糖产生。本研究应用该方法对基因敲除小鼠内源性葡萄糖的产生进行了评价。（自然医学13：332-339，2007; J.Biol.Chem.281：26602-26614，2006）3）肝脏中的葡糖异生可以从质量同位素分布分析（MIDA方法）估计。使用这种方法和另一种示踪技术，在口服葡萄糖和静脉葡萄糖负荷后评估肝脏葡萄糖代谢，以评估门静脉信号。(to日本糖尿病学会第51届年会（2008年）

As the main source of endogenous glucose production in the body, the liver plays a crucial role in glucose homeostasis. Despite the importance of liver and insulin in maintaining normal glucose homeostasis, there is a paucity in literature regarding hepatic insulin sensitivity. The aim of the present research project was 1) to develop new method to estimate hepatic insulin sensitivity from intravenous glucose tolerance test. 2) to evaluate hepatic glucose production in vivo. 3) to evaluate effect of exercise on glucose metabolism including hepatic glucose production and hepatic insulin sensitivity.1) Hepatic insulin sensitivity assessed by integrated model of hepatic and peripheral glucose regulation. Integrated model of hepatic and peripheral glucose metabolism describes exogenous and endogenous glucose kinetics during labeled glucose tolerance test. The model also provides a parametric description of endogenous glucose production. The present study extended the theoretical potential of the model by defining hepatic insulin sensitivity as the ability of insulin to enhance glucose suppression of endogenous glucose production (submitted to Computer Method & Programs in Biomedicine 2007).2) Using stable isotope, endogenous glucose production can be estimated. The present study applied this method to evaluate endogenous glucose production of genetically knock-out mice. (Nature Medicine 13: 332-339, 2007; J. Biol. Chem. 281: 26602-26614, 2006)3) Gluconeogenesis in the liver can be estimated from mass isotopomer distribution analysis (MIDA method). Using this approach and another tracer technique, hepatic glucose metabolism was assessed after oral glucose and intravenous glucose load to evaluate portal signal. (to be presented in 51th Annual Meeting of Japan Diabetes Society 2008)