Effects of exercise on hepatic insulin sensitivity.

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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)