Probing of physiological significance of adipocyte-specific glycerol channel and its application to the treatment of diabetes mellitus.
| Project/Area Number |
15390287
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Osaka University |
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Principal Investigator |
NAKAMURA Tadashi Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (90252668)
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| Co-Investigator(Kenkyū-buntansha) |
FUNAHASHI Tohru Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (60243234)
KIHARA Shinji Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20332736)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2004: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2003: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | aquaporin adipose / aquaporin 9 / glycerol / diabetes mellitus / lipolysis / obesity / knockout mouse / glyconeogenesis / アクアポリンアディポース / PPARγ |
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| Research Abstract |
Aquaporin adipose(AQPap), which we identified from human adipose tissue, is a glycerol channel in adipocyte (J Biol Chem 2000). The expression of this molecule increased in fasting, decreased in feeding and was inhibited by insulin (j Biol Chem 2001). We also demonstrated that there was a coordinated regulation of AQPap and aquaporin 9(AQP9), as a liver specific glycerol channel, through the inhibitory effect by insulin. However, the channel function was dysregulated in obese mice with insulin resistance, leading to glucose intorelance (Diabetes 2002).
In the present study, we investigated glycerol and glucose metabolism in mice lacking AQPap and demonstrated that AQPap functions as a glycerol gateway molecule in vivo. AQPap knockout(KO) mice had lower plasma glycerol levels compared with wild-type(WT) mice but had normal plasma free fatty acid levels. The increase in plasma glycrol level in response to _-adrenergic agonist was severely impaired in KO mice. Epinephrin-stimulated glycerol secretion was also impaired in AQPap knockdown adipocytes. During prolonged fasting, plasma glycerol was elevated and the plasma glucose level was maintained in WT mice. In contrast, KO mice showed a disrupted increase of plasma glycerol and rapid reduction of plasma glucose during prolonged fasting. These findings suggest that the lack of effective glycerol transport from adipocytes by glycerol gateway molecule causes defective adaptation to prolonged fasting. (PNAS 2004).
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Report
(3 results)
Research Products
(25 results)
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[Journal Article] A new simple method for the measurement of visceral fat accumulation by bioelectrical impedance.2005
Author(s)
Ryo M, Maeda K, Onda T, Katashima M, Okumiya A, Nishida M, Yamaguchi T, Funahashi T, Matsuzawa Y, Nakamura T, Shimomura I.
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Journal Title
Diabetes Care. 28(2)
Pages: 451-453
Description
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[Journal Article] Adiponectin I164T mutation is associated with the metabolic syndrome and coronary artery disease.2004
Author(s)
Ohashi K, Ouchi N, Kihara S, Funahashi T, Nakamura T, Sumitsuji S, Kawamoto T, Matsumoto S, Nagaretani H, Kumada M, Okamoto Y, Nishizawa H, Kishida K, Maeda N, Hiraoka H, Iwashima Y, Ishikawa K, Ohishi M, Katsuya T, Rakugi H, Ogihara T, Matsuzawa Y.
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Journal Title
J Am Coll Cardiol 43(7)
Pages: 1195-1200
Description
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[Journal Article] Osaka CAD Study Group. Coronary artery disease ; Association of hypoadiponectinemia with coronary artery disease in men.2003
Author(s)
M.Kumada, S.Kihara, S.Sumitsuji, T.Kawamoto, S.Matsumoto, N.Ouchi, Y.Arita, Y.Okamoto, I.Shimomura, H.Hiraoka, T.Nakamura, T.Funahashi, Y.Matsuzawa
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Journal Title
Arterioscler.Thromb.Vasc.Biol. 23(1)
Pages: 85-89
Description
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[Journal Article] Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue.2003
Author(s)
N.Ouchi, S.Kihara, T.Funahashi, T.Nakamura, M.Nishida, M.Kumada, Y.Okamoto, K.Ohashi, H.Nagaretani, K.Kishida, H.Nishizawa, N.Maeda, H.Kobayashi, H.Hiraoka, Y.Matsuzawa
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Journal Title
Circulation 107(5)
Pages: 671-674
Description
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[Journal Article] Association of hypoadiponectinemia with impaired vasoreactivity.2003
Author(s)
N.Ouchi, M.Ohishi, S.Kihara, T.Funahashi, T.Nakamura, H.Nagaretani, M.Kumada, K.Ohashi, Y.Okamoto, H.Nishizawa, K.Kishida, N.Maeda, A.Nagasawa, H.Kobayashi, H.Hiraoka, N.Komai, M.Kaibe, H.Rakugi, T.Ogihara, Y.Matsuzawa
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Journal Title
Hypertension 42(3)
Pages: 231-234
Description
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