Vaspinのメタボリック症候群における意義

• 研究課題/領域番号: 20390257
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 代謝学
• 研究機関: 岡山大学
• 研究代表者: 和田 淳 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (30294408)
• 研究分担者: 槇野 博史 岡山大学, 大学院・医歯薬学総合研究科, 教授 (50165685)
• 研究期間 (年度): 2008 – 2010
• 研究課題ステータス: 完了 (2010年度)
• 配分額: 18,590千円 (直接経費: 14,300千円、間接経費: 4,290千円); 2010年度: 5,330千円 (直接経費: 4,100千円、間接経費: 1,230千円); 2009年度: 6,240千円 (直接経費: 4,800千円、間接経費: 1,440千円); 2008年度: 7,020千円 (直接経費: 5,400千円、間接経費: 1,620千円)
• キーワード: メタボリックシンドローム / インスリン抵抗性 / アディポカイン / バスピン / 糖尿病 / 脂質異常症 / 高血圧 / 肥満症 / メタボリック症候群 / 肥満

研究概要

Vaspinは肥満ラットの内臓脂肪から発見したアディポサイトカインである。肥満マウスへのリコンビナント蛋白の投与実験・トランスジェニックマウスやノックアウトマウスの実験からメタボリック症候群においてインスリン抵抗性を改善する代償因子であるとの結論に至った。Vaspinはヒトの血中にも存在し、体格指数やインスリン抵抗性指数と正の相関を認め、2型糖尿病でも血中濃度が増加している。アディポネクチンやレプチンとは異なった血中濃度動態を示しておりメタボリック症候群治療の新たな分子ターゲットである。

研究成果

• [雑誌論文] Effects of icodextrin peritoneal dialysis solution on the peritoneal membrane in the STZ-induced diabetic rat model with partial nephrectomy. (2010)
  • 著者名/発表者名: Nakao A, Nakao K, Takatori Y, Kojo S, Inoue J, Akagi S, Sugiyama H, Wada J, Makino H
  • 雑誌名: Nephrol Dial Transplant 25(5) ページ: 1479-1488
  • 査読あり
• [雑誌論文] Comparison of insulin detemir and insulin glargine on glycemic variability in patients with type 1 and type 2 diabetes. (2010)
  • 著者名/発表者名: Tone A, Iseda I, Higuchi C, Tsukamoto K, Katayama A, Matsushita Y, Hida K, Wada J, Shikata K
  • 雑誌名: Exp Clin Endocrinol Diabetes 118(5) ページ: 320-324
  • 査読あり
• [雑誌論文] In vivo delivery of gremlin siRNA plasmid reveals therapeutic potential against diabetic nephropathy by recovering bone morphogenetic protein-7. (2010)
  • 著者名/発表者名: Zhang Q, Shi Y, Wada J, Malakauskas SM, Liu M, Ren Y, Du C, Duan H, Li Y, Li Y, Zhang Y
  • 雑誌名: PLoS ONE 5(7)
  • 査読あり
• [雑誌論文] Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R and their effect on visceral fat area in the Japanese population. (2010)
  • 著者名/発表者名: Hotta K, Nakamura M, Nakamura T, Matsuo T, Nakata Y, Kamohara S, Miyatake N, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Kawamoto M, Masuzaki H, Ueno T, Hamaguchi K, Tanaka K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K, Sakata T, Matsuzawa Y, Nakamura Y, Kamatani N
  • 雑誌名: J Hum Genet 55(11) ページ: 738-742
  • NAID: 10030737572
  • 査読あり
• [雑誌論文] Effects of icodextrin peritoneal dialysis solution on the peritoneal membrane in the STZ-induced diabetic rat model with partial nephrectomy. (2010)
  • 著者名/発表者名: Nakao A, Nakao K, Takatori Y, Kojo S, Inoue J, Akagi S, Sugiyama H, Wada J, Makino H
  • 雑誌名: Nephrol Dial Transplant 巻: 25(5) ページ: 1479-1488
  • 査読あり
• [雑誌論文] Comparison of insulin detemir and insulin glargine on glycemic variability in patients with type 1 and type 2 diabetes. (2010)
  • 著者名/発表者名: Tone A, Iseda I, Higuchi C, Tsukamoto K, Katayama A, Matsushita Y, Hida K, Wada J, Shikata K
  • 雑誌名: Exp Clin Endocrinol Diabetes 巻: 118(5) ページ: 320-324
  • 査読あり
• [雑誌論文] In vivo delivery of gremlin siRNA plasmid reveals therapeutic potential against diabetic nephropathy by recovering bone morphogenetic protein-7 (2010)
  • 著者名/発表者名: Zhang Q, Shi Y, Wada J, Malakauskas SM, Liu M, Ren Y, Du C, Duan H, Li Y, Li Y, Zhang Y
  • 雑誌名: PLoS ONE 巻: 5(7)
  • 査読あり
• [雑誌論文] Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R and their effect on visceral fat area in the Japanese population. (2010)
  • 著者名/発表者名: Hotta K, Nakamura M, Nakamura T, Matsuo T, Nakata Y, Kamohara S, Miyatake N, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Kawamoto M, Masuzaki H, Ueno T, Hamaguchi K, Tanaka K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K, Sakata T, Matsuzawa Y, Nakamura Y, Kamatani N
  • 雑誌名: J Hum Genet 巻: 55(11) ページ: 738-742
  • NAID: 10030737572
  • 査読あり
• [雑誌論文] Screening of 336 single-nucleotide polymorphisms in 85 obesity-related genes revealed McKusick-Kaufman syndrome gene variants are associated with metabolic syndrome. (2009)
  • 著者名/発表者名: Hotta K, Nakamura T, Takasaki J, Takahashi H, Takahashi A, Nakata Y, Kamohara S, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Masuzaki H, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Hamaguchi K, Tanaka K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K, Sakata T, Matsuzawa Y, Kamatani N, Nakamura Y
  • 雑誌名: J Hum Genet 54(4) ページ: 230-235
  • NAID: 10030730053
  • 査読あり
• [雑誌論文] Enhanced interaction between focal adhesion and adherens junction proteins : involvement in sphingosine 1-phosphate-induced endothelial barrier enhancement. (2009)
  • 著者名/発表者名: Sun X, Shikata Y, Wang L, Ohmori K, Watanabe N, Wada J, Shikata K, Birukov KG, Makino H, Jacobson JR, Dudek SM, Garcia JG
  • 雑誌名: Microvasc Res 77(3) ページ: 304-313
  • 査読あり
• [雑誌論文] Endothelial barrier protection by FTY720 under hyperglycemic condition : involvement of focal adhesion kinase, small GTPases, and adherens junction proteins. (2009)
  • 著者名/発表者名: Sarai K, Shikata K, Shikata Y, Omori K, Watanabe N, Sasaki M, Nishishita S, Wada J, Goda N, Kataoka N, Makino H
  • 雑誌名: Am J Physiol Cell Physiol 297(4)
  • 査読あり
• [雑誌論文] Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population. (2009)
  • 著者名/発表者名: Hotta K, Nakamura M, Nakamura T, Matsuo T, Nakata Y, Kamohara S, Miyatake N, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Masuzaki H, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Kawamoto M, Ueno T, Hamaguchi K, Tanaka K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K, Sakata T, Matsuzawa Y, Kamatani N, Nakamura Y
  • 雑誌名: J Hum Genet 54(12) ページ: 727-731
  • NAID: 10030732862
  • 査読あり
• [雑誌論文] Screening of 336 single-nucleotide polymorphisms in 85 obesity-related genes revealed McKusick-Kaufman syndrome gene variants are associated with metabolic syndrome. (2009)
  • 著者名/発表者名: Hotta K, (以下25名省略), Wada J, Nakamura Y
  • 雑誌名: J Hum Genet. 54(4) ページ: 230-235
  • NAID: 10030730053
  • 査読あり
• [雑誌論文] Enhanced interaction between focal adhesion and adberens junction proteins : involvement in sphingosine 1-phosphate-induced endothelial barrier enbancement. (2009)
  • 著者名/発表者名: Sun X, Shikata Y, Wang L, Ohmori K, Watanabe N, Wada J, Shikata K, Birukov KG, Makino H, Jacobson JR, Dudek SM, Garcia JG
  • 雑誌名: Microvasc Res 77(3) ページ: 304-313
  • 査読あり
• [雑誌論文] Urinary excretions of lipocalin-type prostaglandin D synthase predict renal injury in type-2 diabetes : a cross-sectional and prospective multicentre study. (2009)
  • 著者名/発表者名: Uehara Y, Makino H, Seiki K, Urade Y, LPGDS Clinical Research Group of Kidney
  • 雑誌名: Nephrol Dial Transplant 24(2) ページ: 475-482
  • 査読あり
• [雑誌論文] Endothelial barrier protection by FTY720 under hyperglycemic condition : involvement of focal adhesion kinase, small GTPases, and adherens junctionproteins. (2009)
  • 著者名/発表者名: Sarai K, Shikata K, Shikata Y, Omori K, Watanabe N, Sasaki M, Nishishita S, Wada J, Goda N, Kataoka N, Makino H
  • 雑誌名: Am J Physiol Cell Physiol 297(4)
  • 査読あり
• [雑誌論文] Effects of icodextrin peritoneal dialysis solution on the peritoneal membrane in the STZ-induced diabetic rat model with partial nephrectomy. (2009)
  • 著者名/発表者名: Nakao A, Nakao K, Takatori Y, Kojo S, Inoue J, Akagi S, Sugiyama H, Wada J, Makino H
  • 雑誌名: Nephrol Dial Transplant (In press)
  • 査読あり
• [雑誌論文] Procollagen C-proteinase enhancer-1 (PCPE-1) interacts with beta(2)-microglobulin (beta2-m) and may help initiate beta2-m amyloid fibril formation in connective tissues. (2008)
  • 著者名/発表者名: Morimoto H, Wada J, Font B, Mott JD, Hulmes DJ, Ookoshi T, Naiki H, Yasuhara A, Nakatsuka A, Fukuoka K, Takatori Y, Ichikawa H, Akagi S, Nakao K, Makino H
  • 雑誌名: Matrix Biol 27(3) ページ: 211-219
  • 査読あり
• [雑誌論文] Comparison of serum uric acid levels between Japanese with and without metabolic syndrome. (2008)
  • 著者名/発表者名: Numata T, Miyatake N, Wada J, Makino H
  • 雑誌名: Diabetes Res Clin Pract 80(1)
  • 査読あり
• [雑誌論文] Amelioration of high glucose-induced renal cell mitochondrial dysfunction by Rap1b GTPase. (2008)
  • 著者名/発表者名: Sun L, Xie P, Wada J, Kashihara N, Lie F-Y, Zhao Y, Kumar D, Chugh SS, Danesh FR, Kanwar YS
  • 雑誌名: J Am Soc Nephrol 19(12) ページ: 2293-2301
  • 査読あり
• [雑誌論文] Glycated albumin levels predict long-term survival in diabetic patients undergoing hemodialysis. (2008)
  • 著者名/発表者名: Fukuoka K, Nakao K, Morimoto H, Nakao A, Takatori Y, Arimoto K, Taki M, Wada J, Makino H
  • 雑誌名: Nephrology (Carlton) 13(4) ページ: 278-283
  • 査読あり
• [雑誌論文] Variations in the FTO gene are associated with severe obesity in the Japanese. (2008)
  • 著者名/発表者名: Hotta K, Nakata Y, Matsuo T, Kamohara S, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Masuzaki H, Yondeda M, Nakajima A, Miyazaki S, Tokunaga K, Kawamoto M, Funahashi T, Hamaguchi K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K, Sakata T, Matsuzawa Y, Tanaka K, Kamatani N, Nakamura Y
  • 雑誌名: J Hum Genet 53(6) ページ: 546-553
  • NAID: 10021249391
  • 査読あり
• [雑誌論文] INSIG2 gene rs7566605 polymorphism is associated with severe obesity in Japanese. (2008)
  • 著者名/発表者名: Hotta K, Nakamura M, Nakata Y, Matsuo T, Kamohara S, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Masuzaki H, Yoneda M, Nakajima A, Miyazaki S, Tokunaga K, Kawamoto M, Funahashi T, Hamaguchi K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K, Sakata T, Matsuzawa Y, Tanaka K, Kamatani N, Nakamura Y
  • 雑誌名: J Hum Genet 53(9) ページ: 857-862
  • NAID: 10021929575
  • 査読あり
• [雑誌論文] Collectrin is involved in the development of salt-sensitive hypertension by facilitating the membrane trafficking of apical membrane proteins via interaction with SNARE complex. (2008)
  • 著者名/発表者名: Yasuhara A, Wada J, Malakauskas SM, Zhang Y, Eguchi J, Nakatsuka A, Murakami K, Kanzaki M, Teshigawara S, Yamagata K, Le TH, Makino H
  • 雑誌名: Circulation 118 ページ: 2146-2155
  • 査読あり
• [雑誌論文] Procollagen C-proteinase enhancer-1 (PCPE-1)interacts with beta(2)-microglobulin (beta2-m)and may help initiate beta2-mamyloid fibril formation in connective tissues. (2008)
  • 著者名/発表者名: Morimoto H, Wada J, FontB, Mott JD, Hulmes DJ, Ookoshi T, Naiki H, Yasuhara A, Nakatsuka A, Fukuoka K, Takatori Y, Ichikawa H, Akagi S, Nakao K, Makino H
  • 雑誌名: Matrix Biol 27(3) ページ: 211-219
  • 査読あり
• [雑誌論文] Comparison of serum uric acid levels between Japanese with and without metabolic syndrome. (2008)
  • 著者名/発表者名: Numata T, Miyatake N, Wada J, Makino H
  • 雑誌名: Diabetes Res Clin Prac 80(1)
  • 査読あり
• [雑誌論文] Vaspin : a novel serpin with insulin-sensitizing effects. (2008)
  • 著者名/発表者名: Wada J
  • 雑誌名: Expert Opin lnvestig Drugs 17(3) ページ: 327-333
  • 査読あり
• [雑誌論文] Diabetic nephropathy : mechanism of renal disease progression. (2008)
  • 著者名/発表者名: Kanwar YS, Wada J. Sun L, Xie P, Wallner El, Chen s, Chugh s, Danesh FR
  • 雑誌名: Exp Biol Med (Maywood) 233(1) ページ: 4-11
  • 査読あり
• [雑誌論文] Variations in the FTO gene are associated with severe obesity in the Japanese. (2008)
  • 著者名/発表者名: Hotta K, Nakata Y, Matsuo T, Kamohara S, Kotani K, Komatsu R, ltoh N, Mineo I, Wada J, Masuzaki H, Yondeda M, Nakajima A, Miyazaki S, Tokunaga K, Kawamoto M, Funahashi T, Hamaguchi K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K, Sakata T, Matsuzawa Y, Tanaka K, Kamatani N, Nakamura Y
  • 雑誌名: J Hum Genet 53(6) ページ: 546-553
  • NAID: 10021249391
  • 査読あり
• [雑誌論文] INSIG2 gene rs7566605 polymorphism is associated with severe obesity in Japanese. (2008)
  • 著者名/発表者名: Hotta, K, Nakamura, M, Nakata, Y, Matsuo, T, Kamohara, S, Kotani, K, Komatsu, R, ltoh, N, Mineo, |, Wada, J, Masuzaki, H, Yoneda, M, Nakajima, A, Miyazaki, S, Tokunaga, K, Kawamoto, M, Funahashi, T, Hamaguchi, K, Yamada, K, Hanafusa, T, Oikawa, S, Yoshimatsu, H, Nakao, K, Sakata, T, Matsuzawa, Y, Tanaka, K, Kamatani, N, Nakamura, Y
  • 雑誌名: J Hum Genet 53(9) ページ: 857-862
  • NAID: 10021929575
  • 査読あり
• [雑誌論文] Collectrin is involved in the development of salt-sensitive hypertension by facilitating the membrane trafficking of apicalmembrane proteins via interaction with SNARE complex. (2008)
  • 著者名/発表者名: Yasuhara A, Wada J, Malakauskas SM, Zhang Y, Eguchi J, Nakatsuka A, Murakami K, Kanzaki M, Teshigawara S, Yamagata K, Le TH, Makino H
  • 雑誌名: Circulation 118 ページ: 2146-2155
  • 査読あり
• [学会発表] コレクトリン:その機能と異常 (2010)
  • 著者名/発表者名: 和田淳
  • 学会等名: 第53回日本腎臓学会
  • 発表場所: 神戸ポートピアホテル(神戸市)
  • 年月日: 2010-06-16
• [学会発表] Vaspin as a New Therapeutic Target for Diabetes and Obesity. (2009)
  • 著者名/発表者名: Wada J
  • 学会等名: BIT Life Sciences' 7^<th> Annual Congress of International Drug Discovery Sciences & Technology-2009
  • 発表場所: Shanghai, China
  • 年月日: 2009-10-24
• [学会発表] Vaspin as a New Therapeutic Target for Diabetes and Obesity. (2009)
  • 著者名/発表者名: Wada J, 他 共著
  • 学会等名: BIT Life Sciences' 7th Annual Congress of International Drug Discovery Sciences & Technology-2009
  • 発表場所: 上海
  • 年月日: 2009-10-24
• [学会発表] Vaspin, A Novel Adipokine with Insulin-Sensitizing Effects. (2008)
  • 著者名/発表者名: Wada J
  • 学会等名: GTCbio's 4th Metabolic Diseases World Summit
  • 発表場所: Boston, USA
  • 年月日: 2008-11-06
• [学会発表] Vaspin, A Novel Adipokine with Insulin Sensitizing Effects. (2008)
  • 著者名/発表者名: Wada J
  • 学会等名: GTCbio's 4th Metabolic Diseases World Summit
  • 発表場所: Boston, US
  • 年月日: 2008-11-06
• [学会発表] Drug discovery related to vaspin, visceral adipose tissue-derived serine protease inhibitor, a novel adipokine with insulin-sensitizing effects. (2008)
  • 著者名/発表者名: Wada J
  • 学会等名: EHRLICH II, 2nd World Conference on Magic Bullets
  • 発表場所: Nurnberg, Germany
  • 年月日: 2008-10-04
• [図書] Vaspin : Visceral Adipose Tissue-Derived Serpin with Insulin-Sensitizing Effects(Ed Bojidor Georgiev and Sava Markovski)(In Serpins and Protein Kinase Inhibitors : Novel Functions, Structural Features and Molecular Mechanisms, Nova Science Publishers, Hauppauge NY) (2009)
  • 著者名/発表者名: Wada J
• [図書] Serpins and Protein Kinase Inhibitors : Novel Functions, Structural Features and Molecular Mechanisms (2009)
  • 著者名/発表者名: Wada J
  • 総ページ数: 257
  • 出版者: Nova Science Publishers