Effects of exercise on hepatic insulin sensitivity.

• Project/Area Number: 17300205
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Sports science
• Research Institution: University of Tsukuba
• Principal Investigator: TOKUYAMA Kumpei University of Tsukuba, Graduate School of Comprehensive Human Science, Professor (00207565)
• Co-Investigator(Kenkyū-buntansha): NAGANSAKA Shoichiro Jichi Medical University, 医学部, Assistant Professor (00296112) ; TANAKA Kiyoji University of Tsukuba, Graduate School of Comprehensive Human Science, Professor (50163514)
• Project Period (FY): 2005 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥13,690,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥990,000); Fiscal Year 2007: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2006: ¥4,600,000 (Direct Cost: ¥4,600,000); Fiscal Year 2005: ¥4,800,000 (Direct Cost: ¥4,800,000)
• Keywords: minimal model / stable isotope / insulin resistance / diabetes / intervention with exercise / glucose effective / hepatic glucose production / 糖尻病 / 安定同位体 / インスリン感受性 / 血糖の日内変動 / フラクタル解析 / minimal model / ヒューマン・カロリメータ / 運動介入 / 肝臓 / 運動 / シミュレーション

Research Abstract

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)

Research Products

• [Journal Article] Continuous glucose monitoring (2008)
  • Author(s): Ogata, H., K. Tokuyama
  • Journal Title: Annual Review of Diabetes, Metabolism and Endocrinology Pages: 44-50
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions (2007)
  • Author(s): Yamauchi T, Y. Nio, T. Maki, M. Kobayashi, T. Takazawa, M. Iwabu, M. Okada-lwabu, S. Kawamoto, N. Kubota, T. Kubota, Y. Ito, J. Kamon, A. Tsuchida, K. Kumagai, H. Kozono, Y. Hada, H. Ogata, K. Tokuyama, M. Tsunoda, T. Ide, K. Murakami, M. Awazawa, I. Takamoto, P. Froguel, K. Hara, K. Tobe, R. Nagai, K. Ueki, T. Kadowaki
  • Journal Title: Nature Medicine 13 Pages: 332-339
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Improved transient response of whole body indirect calorimeter by deconvolution (2007)
  • Author(s): Tokuyama, K., M. Sato, H. Ogata, S. Maritani, S. Nakajima.
  • Journal Title: Japanese Journal of Physical Fitness and Sports Medicine. 56 Pages: 315-326
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. (2007)
  • Author(s): Yamauchi T, Y. Nio, T. Maki, M. Kobayashi, T. Takazawa, M. Iwabu, M. Okada-lwabu, S. Kawamoto, N. Kubota, T. Kubota, Y. Ito, J. Kamon, A. Tsuchida, K. Kumagai, H. Kozono, Y. Hada, H. Ogata, K. Tokuyama, M. Tsunoda, T. Ide, K. Murakami, M. Awazawa, I.Takamoto, P. Froguel, K. Hara, K. Tobe, R. Nagai, K. Ueki, T. Kadowaki.
  • Journal Title: Nature Medicine 13 Pages: 332-339
  • Peer Reviewed
• [Journal Article] Improved transient response of whole body indirect calorimeter by deconvolution. (2007)
  • Author(s): Tokuyama, K., M. Sato, H. Ogata, S. Maritani, S. Nakajima
  • Journal Title: Japanese Journal of Physical Fitness and Sports Medicine. 56 Pages: 315-326
  • Peer Reviewed
• [Journal Article] Log-range negative correlation of glucose dynamics in humans and its breakdown in diabetes mellitus (2006)
  • Author(s): Ogata, H., K. Tokuyama, S. Nagasaka, A. Ando, I. Kusaka, N. Sato, A. Goto, S. Ishibashi, K. Kiyono, Z. R. Struzik, Y. Yamamoto.
  • Journal Title: American Journal of Physiology Regulatory Integrative and Comparative Physiology 291
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance (2006)
  • Author(s): Kamei, N., K. Tbbe, R. Suzuki, M. Ohsugi, T. Watanabe, N. Kubota, N. Ohtsuka-Kowatari, K. Kumagai, K. Sakamoto, M. Kobayashi, T. Yamauchi, K. Ueki, Y. Oishi, S. Nishimura, I. Manabe, H. Hashimoto, Y. Ohnishi, H. Ogata, K. Tokuyama, M. Tsunoda, T. Ide, K. Murakami, R. Nagai, T. Kadowaki
  • Journal Title: Journal of Biological Chemistry 281 Pages: 26602-26614
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 食後体熱産生のcephalic phase : ヒューマン・カロリメータによる検討 (2006)
  • Author(s): 山内有, 佐藤真樹, 徳山薫平
  • Journal Title: 肥満研究 12 Pages: 131-135
  • NAID: 10018715032
• [Journal Article] Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and-independent pathways. (2006)
  • Author(s): KUbota, N., Y.Terauchi, T.Kubota, H.Kumagai, S.Itoh, W.Yano, H.Ogata, K.Tokuyama, I.Takamoto, T.Mineyama, M.Ishikawa, M.Moroi, K.Sugi, T.Yamauchi, K.Ueki, K.Tobe, T.Noda, R.Nagai, T.Kadowaki.
  • Journal Title: J.Biol.Chem. 281 Pages: 8748-8755
• [Journal Article] Log-range negative correlation of glucose dynamics in gumans band its breakdown in diabetes mellitus. (2006)
  • Author(s): Ogata, H., K.Tokuyama, S.Nagasaka, A.Ando, I.Kusaka, N.Sato, A.Goto, S.Ishibashi, K.Kiyono, Z.R.Struzik, Y.Yamamoto.
  • Journal Title: Am.J.Physiol. 291
• [Journal Article] Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. (2006)
  • Author(s): Kamei, N., K.Tobe, R.Suzuki, M.Ohsugi, T.Watanabe, N.Kubota, N.Ohtsuka-Kowatari, K.Kumagai, K.Sakamoto, M.Kobayashi, T.Yamauchi, K.Ueki, Y.Oishi, H.Ogata, K.Tokuyama, M.Tsunoda, T.Ide, K.Murakami, R.Nagai, T.Kadowaki
  • Journal Title: J.Biol.Chem. 281 Pages: 26602-26614
• [Journal Article] A single bout of exercise at higher intensity enhances glucose effectiveness in sedentary men. (2005)
  • Author(s): Hayashi, Y., S.Nagasaka, N.Takahashi, I.Kusaka, S.Ishibashi, S.Numao, D.-J.Lee, Y.Taki, H.Ogata, K.Tokuyama, K.Tanaka.
  • Journal Title: J.Clin.Endocrinol.Metab. 90・7 Pages: 4035-4040
• [Presentation] ヒューマンカロリメータによるエネルギー代謝測定 (2007)
  • Author(s): 徳山薫平
  • Organizer: 第60回日本栄養食糧学会
  • Place of Presentation: 京都
  • Year and Date: 2007-05-18
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Evaluation of energy metabolism by human calorimeter (2007)
  • Author(s): Tokuyama K.
  • Organizer: 60th Scientific meeting of Japanese Society of Nutrition and Food Science
  • Place of Presentation: Kyoto
  • Year and Date: 2007-05-18
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Annual Review 糖尿病・代謝・内分泌 (2008)
  • Author(s): 緒形ひとみ・徳山薫平
  • Publisher: 中外医学社
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Annual Review糖尿病・代謝・内分泌 (2008)
  • Author(s): 緒形ひとみ、徳山薫平
  • Publisher: 中外医学社