Effects of exercise on hepatic insulin sensitivity.

作为体内内源性葡萄糖生产的主要来源，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)建立静脉葡萄糖耐量试验估计肝脏胰岛素敏感性的新方法。2)评估体内肝脏葡萄糖生成。3)评价运动对糖代谢的影响，包括肝糖生成和肝胰岛素敏感性。1)肝外周葡萄糖调节综合模型评价肝脏胰岛素敏感性。肝脏和外周糖代谢的综合模型描述了标记糖耐量试验中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生产的参数描述。本研究通过将肝脏胰岛素敏感性定义为胰岛素增强葡萄糖抑制内源性葡萄糖产生的能力，扩展了该模型的理论潜力（提交给2007年生物医学计算机方法和程序）。2)利用稳定同位素，可以估算内源性葡萄糖产量。本研究应用该方法评价基因敲除小鼠的内源性葡萄糖生成。[j] .中华医学杂志，2007；3)肝脏糖异生可以通过质量同位素分布分析（MIDA法）来估计。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，以评估门脉信号。（将于2008年日本糖尿病学会第51届年会上发表）

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)