Ｖａｓｐｉｎのメタボリック症候群における意義と創薬への展開

2013 年度 研究成果報告書

• 研究課題/領域番号: 23390241
• 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, 医歯(薬)学総合研究科, 准教授 (30294408)
• 研究期間 (年度): 2011-04-01 – 2014-03-31
• 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

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。メタボリックシンドロームにおいてインスリン抵抗性を改善し、動脈硬化の進展を抑制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] Pemt deficiency ameliorates endoplasmic reticulum stress in diabetic nephropathy (2014)
  • 著者名/発表者名: Watanabe M, Nakatsuka A, Murakami K, Inoue K, Terami T, Higuchi C, Katayama A, Teshigawara S, Eguchi J, Ogawa D, Watanabe E, Wada J, Makino H
  • 雑誌名: PLoS ONE 巻: 9(3) ページ: e92647
  • DOI: 10.1371/journal.pone.0092647
  • 査読あり
• [雑誌論文] Nuclear hormone receptor expression in mouse kidney and renal cell lines (2014)
  • 著者名/発表者名: Ogawa D, Eguchi J, Wada J, Terami N, Hatanaka T, Tachibana H, Nakatsuka A, Horiguchi CS, Nishii N, Makino H
  • 雑誌名: PLoS ONE 巻: 9(1) ページ: e85594
  • DOI: 10.1371/journal.pone.0085594
  • 査読あり
• [雑誌論文] Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice (2014)
  • 著者名/発表者名: Tachibana H, Ogawa D, Sogawa N, Asanuma M, Miyazaki I, Terami N, Hatanaka T, Horigushi CS, Nakatsuka A, Eguchi J, Wada J, Yamada H, Takei K, Makino H
  • 雑誌名: Am J Physiol Renal Physiol 巻: 306 ページ: F105-F115
  • DOI: 10.1152/ajprenal.00034.2013
  • 査読あり
• [雑誌論文] Long-term effect of cinacalcet hydrochloride on abdominal aortic calcification in patients on hemodialysis with secondary hyperparathyroidism (2013)
  • 著者名/発表者名: Nakayama K, Nakao K, Takatori Y, Inoue J, Kojo S, Akagi S, Fukushima M, Wada J, Makino H
  • 雑誌名: Int J Nephrol Renovasc Dis 巻: 7 ページ: 25-33
  • DOI: 10.2147/IJNRD.S54731
  • 査読あり
• [雑誌論文] Urinary angiotensinogen is a marker for tubular injuries in patients with type 2 diabetes (2013)
  • 著者名/発表者名: Terami T, Wada J, Inoue K, Nakatsuka A, Ogawa D, Teshigawara S, Murakami K, Katayama A, Eguchi J, Makino H
  • 雑誌名: Int J Nephrol Renovasc Dis 巻: 6 ページ: 233-240
  • DOI: 10.2147/IJNRD.S51829
  • 査読あり
• [雑誌論文] Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease (2013)
  • 著者名/発表者名: Kurose Y, Wada J, Kanzaki M, Teshigawara S, Nakatsuka A, Murakami K, Inoue K, Terami T, Katayama A, Watanabe M, Higushi C, Eguchi J, Miyatake N, Makino H
  • 雑誌名: BMC Nephrol 14 巻: 14 ページ: 23
  • DOI: 10.1186/1471-2369-14-23
  • 査読あり
• [雑誌論文] Vaspin inhibits apoptosis of endothelial cells as a ligand for cell-surface GRP78/VDAC complex (2013)
  • 著者名/発表者名: Nakatsuka A, Wada J, Iseda I, Teshigawara S, Higashio K, Murakami K, Kanzaki M, Inoue K, Terami T, Katayama A, Hida K, Eguchi J, Ogawa D, Matsuki Y, Hiramatsu R, Tagita H, Kakuta S, Iwakura Y, Makino H
  • 雑誌名: Circ Res 巻: 112(5) ページ: 771-780
  • DOI: 10.1161/CIRCRESAHA.111.300049
  • 査読あり
• [雑誌論文] The effects of telmisartan treatment on the abdominal fat depot in patients with metabolic syndrome and essential hypertension : Abdominal fat Depot Intervention Program of Okayama (ADIPO) (2013)
  • 著者名/発表者名: Murakami K, Wada J, Ogawa D, Horiguchi CS, Miyoshi T, Sasaki M, Uchida HA, Nakamura Y, Makino H
  • 雑誌名: Diab Vasc Dis Res 巻: 10(1) ページ: 93-96
  • DOI: 10.1177/1479164112444640
  • 査読あり
• [雑誌論文] Telmisartan attenuates diabetic nephropathy by suppressing ixidative stress in db/db mice (2012)
  • 著者名/発表者名: Sato-Horiguchi C, Ogawa D, Wada J, Tachibana H, Kodera R, Eguchi J, Nakatsuka A, Terami N, Shikata K, Makino H
  • 雑誌名: Nephron Exp Nephrol 巻: 121(3-4) ページ: e97-e108
  • DOI: 10.1159/000343102
  • 査読あり
• [雑誌論文] The serum vaspin levels are reduced in Japanese chronic hemodialysis patients (2012)
  • 著者名/発表者名: Inoue J, Wada J, Teshigawara S, Hida K, Nakatsuka A, Takatori U, Kojo S, Akagi S, Nakao K, Miyatake N, McDonald JF, Makino H
  • 雑誌名: BMC Nephrol 巻: 13(1) ページ: 163
  • DOI: 10.1186/1471-2369-13-163
  • 査読あり
• [雑誌論文] Activation of liver X receptor inhibits osteopontin and ameliorates diabetic nephropathy (2012)
  • 著者名/発表者名: Tachibana H, Ogawa D, Matsushita Y, Bruemmer D, Wada J, Teshigawara S, Eguchi J, Horiguchi CS, Uchida HA, Shikata K, Makino H
  • 雑誌名: J Am Soc Nephrol 巻: 23(11) ページ: 1835-1846
  • DOI: 10.1681/ASN.2012010022
  • 査読あり
• [雑誌論文] Vaspin is an adipokine ameliorating ER stress in obesity as a ligand for cell-surface GRP78/MTJ-1 complex (2012)
  • 著者名/発表者名: Nakatsuka A, Wada J, Iseda I, Teshigawara S, Higashio K, Murakami K, Kanzaki M, Inoue K, Terami T, Katayama A, Hida K, Eguchi J, Horiguchi CS, Ogawa D, Matsuki Y, Hiramatsu R, Yagita H, Kakuta S, Iwakura Y, Makino H
  • 雑誌名: Diabetes 巻: 61(11) ページ: 2823-2832
  • DOI: 10.2337/db12-0232
  • 査読あり
• [雑誌論文] The therapeutic potential of synthetic human atrial natriuretic peptide in nephrotic syndrome : a randomized controlled trial (2012)
  • 著者名/発表者名: Kanzaki M, Wada J, Kikumoto Y, Akagi S, Nakao K, Sugiyama H, Makino H
  • 雑誌名: Int J Nephrol Renovasc Dis 巻: 5 ページ: 91-96
  • DOI: 10.2147/IJNRD.S32191
  • 査読あり
• [雑誌論文] Hydrogen-rich water prevents progression of non-alcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice (2012)
  • 著者名/発表者名: Kawai D, Takaki A, Nakatsuka A, Wada J, Tamaki N, Yasunaka T, Koike K, Tsuzaki R, Matsumoto K, Miyake Y, Shiraha H, Morita M, Makino H, Yamamoto K
  • 雑誌名: Hepatology 巻: 56(3) ページ: 912-921
  • DOI: 10.1002/hep.25782
  • 査読あり
• [雑誌論文] Serum vaspin concentrations are closely related to insulin resistance and rs77060950 at SERPINA12 genetically defines distinct group with higher serum levels in Japanese population (2012)
  • 著者名/発表者名: Teshigawara S, Wada J, Hida K, Nakatsuka A, Eguchi J, Murakami K, Kanzaki M, Inoe K, Terami T, Katayama A, Iseda I, Matsushita Y, Miyatake N, McDonald JF, Hotta K, Makino H
  • 雑誌名: J Clin Endocrinol Metab 巻: 97(7) ページ: E1202-1207
  • DOI: 10.1210/jc.2011-3297
  • 査読あり
• [雑誌論文] Galectin-9 and T cell immunoglobulin mucin-3 pathway is a therapeutic target for type 1 diabetes (2012)
  • 著者名/発表者名: Kanzaki M, Wada J, Sugiyama K, Nakatsuka A, Teshigawara S, Murakami K, Inoue K, Terami T, Katayama A, Eguchi J, Akiba H, Yagita H, Makino H
  • 雑誌名: Endocrinology 巻: 153(2) ページ: 612-620
  • DOI: 10.1210/en.2011-1579
  • 査読あり
• [雑誌論文] Impact of circulating vaspin levels on metabolic variables in elderly twins (2012)
  • 著者名/発表者名: Hida K, Poulsen P, Teshigawara S, Nilsson E, Friedrichsen M, Ribel-Madsen R, Grunnet L, Lund SS, Wada J, Vaag A
  • 雑誌名: Diabetologia 巻: 55(2) ページ: 530-532
  • DOI: 10.1007/s00125-011-2385-0
  • 査読あり
• [雑誌論文] RXR antagonism induces G0/G1 cell cycle arrest and ameliorates obesity by up-regulating the p53-p21 Cip1 pathway in adipocytes (2012)
  • 著者名/発表者名: Nakatsuka A, Wada J, Hida K, Hida A, Eguchi J, Teshigawara S, Murakami K, Kanzaki M, Inoue K, Terami T, Katayama A, Ogawa D, Kagechika H, Makino H
  • 雑誌名: J Pathol 巻: 226(5) ページ: 784-795
  • DOI: 10.1002/path.3001
  • 査読あり
• [雑誌論文] High glucose increases metallothionein expression in renal proximal tubular epithelial cells (2011)
  • 著者名/発表者名: Ogawa D, Asanuma M, Miyazaki I, Tachibana H, Wada J, Sogawa N, Sugaya T, Kitamura S, Maeshima Y, Shikata K, Makino H
  • 雑誌名: Exp Diabetes Res 巻: 2011 ページ: 534872
  • DOI: 10.1155/2011/534872
  • 査読あり
• [雑誌論文] Icodextrin increases technique survival rate in peritoneal dialysis patients with diabetic nephropathy by improving body fluid management : a randomized controlled trial (2011)
  • 著者名/発表者名: Takatori Y, Akagi S, Sugiyama H, Inoue J, Kojo S, Morinaga H, Nakao K, Wada J, Makino H
  • 雑誌名: Clin J Am Soc Nephrol 巻: 6(6) ページ: 1337-1344
  • DOI: 10.2215/CJN.10041110
  • 査読あり
• [雑誌論文] Urinary fetuin-A is a novel marker for diabetic neohropathy in type 2 diabetes identified by lectin microarray
  • 著者名/発表者名: Inoue K, Wada J, Eguchi J, Nakatsuka A, Teshigawara S, Murakami K, Ogawa D, Terami T, Katayama A, Tone A, Iseda I, Hida K, Yamada M, Ogawa T, Makino H
  • 雑誌名: PLoS ONE 巻: 8(10) ページ: e77118
  • DOI: 10.1371/journal.pone.0077118
  • 査読あり
• [学会発表] T Soluble form of transmembrane protein, Gpnmb, is a novel adipokine with a protective role in fatty liver diseases in obesity (2013)
  • 著者名/発表者名: Katayama A, Wada J, Nakatsuka A, Eguchi J, Murakami K, Kanzaki M, Teshigawara S, Terami T, Inoue K, Hida K, Makino H
  • 学会等名: Keystone Symposia 'Adipose Tissue Biology'
  • 発表場所: Keystone, Colorado, USA
  • 年月日: 20130127-0201
• [学会発表] The pathological role of galectin-9 in metabolic syndrome (2013)
  • 著者名/発表者名: Teshigawara S, Wada J, Kanzaki M, Nakatsuka A, Murakami K, Katayama A, Terami T, Inoue K, Eguchi J, Makino H
  • 学会等名: Keystone Symposia 'Adipose Tissue Biology'
  • 発表場所: Keystone, Colorado, USA
  • 年月日: 20130127-0201
• [学会発表] Phosphatidylethanolamine N-methyltransferase (PEMT) deficiency improves obesity and insulin resistance associated with unexpected progression of steatoheptitis (2013)
  • 著者名/発表者名: Nakatsuka A, Wada J, Murakami K, Kanzaki M, Terami T, Katayama A, Eguchi J, Makino H
  • 学会等名: Keystone Symposia 'Adipose Tissue Biology'
  • 発表場所: Keystone, Colorado, USA
  • 年月日: 20130127-0201
• [学会発表] ACAM (Adipocyte Adhesion Molecule) / CLMP Inhibits Adipocyte Hypertrophy in Obesity (2013)
  • 著者名/発表者名: Murakami K, Wada J, Eguchi J, Ogawa D, Terami T, Terami N, Makino H
  • 学会等名: ADA 73th Scientific Session
  • 発表場所: Chicago
  • 年月日: 2013-06-23
• [学会発表] Phosphatidylethanolamine N-Methyltransferase (PEMT) Deficiency Protects from Obesity and Insulin Resistance but Promote Steatoheptitis with Tumorigenesis (2013)
  • 著者名/発表者名: Nakatsuka A, Wada J, Murakami K, Terami T, Eguchi J, Ogawa D, Makino H
  • 学会等名: ADA 73th Scientific Session
  • 発表場所: Chicago
  • 年月日: 2013-06-23
• [学会発表] Nuclear Hormone Receptor Expression in Mouse Kidney and Renal Cell Lines (2013)
  • 著者名/発表者名: Ogawa D, Eguchi J, Tachibana H, Sato-Horiguchi C, Hatanaka T, Nakatsuka A , Wada J, Makino H
  • 学会等名: ADA 73th Scientific Session
  • 発表場所: Chicago
  • 年月日: 2013-06-22
• [学会発表] Identification of transmembrnane proteins expressed in adipocytes under obese-state and the roles soluble forms in fat accumulation (2012)
  • 著者名/発表者名: Wada J
  • 学会等名: International Symposium for the Study ofObesity "Translational Science and Epidemiology on Adipomedicine; From Lipodystrophy to Obesity"
  • 発表場所: Shiran Kaikan of Kyoto University, Kyoto
  • 年月日: 20121013-14
  • 招待講演
• [学会発表] The pathological role of galectin-9 in metabolic syndrome; Modulation of inflammatory responses in liver and adipose tissue (2012)
  • 著者名/発表者名: Kanzaki M, Wada J, Nakatsuka A, Murakami K, Teshigawara S, Katayama A, Terami T, Inoue K, Eguchi J, Makino H
  • 学会等名: Keystone Symposia, Genetic and Molecular Basis of Obesity and Body Weight Regulation
  • 発表場所: Santa Fe, New Mexico, USA
  • 年月日: 2012-12-01
• [学会発表] Phosphatidylethanolamine N-methyltransferase (PEMT) deficiency protects from obesity and insulin resistance but aggravates non-alcoholic steatoheptitis (NASH) (2012)
  • 著者名/発表者名: Nakatsuka A, Wada J, Murakami K, Kanzaki M, Terami T, Katayama A, Eguchi J, Makino H
  • 学会等名: Keystone Symposia, Genetic and Molecular Basis of Obesity and Body Weight Regulation
  • 発表場所: Santa Fe, New Mexico, USA
  • 年月日: 2012-12-01