Roles of wingless-related MMTV integration site 5B in type 2 diabetes mellitus

• Project/Area Number: 20700566
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Applied health science
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KUBOTA Hiroyuki The Institute of Physical and Chemical Research, 内分泌・代謝疾患研究チーム, 研究員 (40323290)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: WNT5B / インスリン分泌 / ラ氏島 / 脂肪細胞 / トリグリセリド蓄積

Research Abstract

In this study, we examined the effects of wingless-type mammary tumor virus integration-site family member 5B (WNT5B) on insulin secretion by using islets isolated from mouse. Overexpression of WNT5B in the islets increased both basal and glucose-induced insulin secretion from the islets, however, did not induce insulin expression. From the current study, wnt5b may be involved in the progression of type 2 diabetes by modulating insulin secretion from islets.

Research Products

• [Journal Article] A Single Nucleotide Polymorphism within the Acetyl-Coenzyme A Carboxylase Beta Gene Is Associated with Proteinuria in Patients with Type 2 Diabetes. (2010)
  • Author(s): Maeda S, Kobayashi MA, Araki S, Babazono T, Freedman BI, Bostrom MA, Cooke JN, Toyoda M, Umezono T, Tarnow L, Hansen T, Gaede P, Jorsal A, Ng DP, Ikeda M, Yanagimoto T, Tsunoda T, Unoki H, Kawai K, Imanishi M, Suzuki D, Shin HD, Park KS, Kashiwagi A, Iwamoto Y, Kaku K, Kawamori R, Parving HH, Bowden DW, Pedersen O, Nakamura Y.
  • Journal Title: PLoS Genet. 6(2)
  • Peer Reviewed
• [Journal Article] A Single Nucleotide Polymorphism within the Acetyl-Coenzyme A Carboxylase Beta Gene Is Associated with Proteinuria in Patients with Type 2 Diabetes (2010)
  • Author(s): Maeda S et al.
  • Journal Title: PLoS Genet. 6(2)
  • Peer Reviewed
• [Journal Article] Transcription factor AP-2 beta inhibits glucose-induced insulin secretion in cultured insulin-secreting cell-line. (2009)
  • Author(s): Tsukada S, Kobayashi M, Omori S, Unoki H, Maeda S.
  • Journal Title: Diabetes Res Clin Pract. 85(3) Pages: 279-85
  • Peer Reviewed
• [Journal Article] The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load. (2009)
  • Author(s): Holmkvist J, Banasik K, Andersen G, Unoki H, Jensen TS, Pisinger C, Borch-Johnsen K, Sandbaek A, Lauritzen T, Brunak S, Maeda S, Hansen T, Pedersen O.
  • Journal Title: PLoS One 4(6)
  • Peer Reviewed
• [Journal Article] Transcription factor AP-2 beta inhibits glucose-induced insulin secretion in cultured insulin-secreting cell-line (2009)
  • Author(s): Tsukada S et al.
  • Journal Title: Diabetes Res Clin Pract. 85(3) Pages: 279-285
  • Peer Reviewed
• [Journal Article] The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load (2009)
  • Author(s): Holmkvist J et al.
  • Journal Title: PLoS One. 4(6)
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase 2 improves the transplanted adipocyte survival in mice. (2008)
  • Author(s): Kuramochi D, Unoki H, Bujo H, Kubota Y, Jiang M, Rikihisa N, Udagawa A, Yoshimoto S, Ichinose M, Saito Y.
  • Journal Title: Eur J Clin Invest. 38(10) Pages: 752-9
  • Peer Reviewed
• [Journal Article] SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. (2008)
  • Author(s): Unoki H, Takahashi A, Kawaguchi T, Hara K, Horikoshi M, Andersen G, Ng DP, Holmkvist J, Borch-Johnsen K, Jorgensen T, Sandbaek A, Lauritzen T, Hansen T, Nurbaya S, Tsunoda T, Kubo M, Babazono T, Hirose H, Hayashi M, Iwamoto Y, Kashiwagi A, Kaku K, Kawamori R, Tai ES, Pedersen O, Kamatani N, Kadowaki T, Kikkawa R, Nakamura Y, Maeda S.
  • Journal Title: Nat Genet. 40(9) Pages: 1098-102
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase-3 enhances the free fatty acids-induced VEGF expression in adipocytes through toll-like receptor 2. (2008)
  • Author(s): Kawamura T, Murakami K, Bujo H, Unoki H, Jiang M, Nakayama T, Saito Y.
  • Journal Title: Exp Biol Med. 233(10) Pages: 1213-21
  • Peer Reviewed
• [Journal Article] Ang II-stimulated migration of vascular smooth muscle cells is dependent on LR11 in mice. (2008)
  • Author(s): Jiang M, Bujo H, Ohwaki K, Unoki H, Yamazaki H, Kanaki T, Shibasaki M, Azuma K, Harigaya K, Schneider WJ, Saito Y.
  • Journal Title: J Clin Invest. 118(8) Pages: 2733-46
  • Peer Reviewed
• [Journal Article] Advanced glycation end products and insulin resistance. (2008)
  • Author(s): Unoki H, Yamagishi S.
  • Journal Title: Curr Pharm Des. 14(10) Pages: 987-9
  • Peer Reviewed
• [Journal Article] Macrophages regulate tumor necrosis factor-・expression in adipocytes through the secretion of matrix metalloproteinase-3. (2008)
  • Author(s): Unoki H, Bujo H, Jiang M, Kawamura T, Murakami K, Saito Y.
  • Journal Title: Int J Obes. 32(6) Pages: 902-11
  • Peer Reviewed
• [Journal Article] Low-dose GH supplementation reduces the TLR2 and TNF-・expressions in visceral fat. (2008)
  • Author(s): Kubota Y, Unoki H, Bujo H, Rikihisa N, Udagawa A, Yoshimoto S, Ichinose M, Saito Y.
  • Journal Title: Biochem Biophys Res Commun. 28,368(1) Pages: 81-7
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase 2 improves the transplanted adipocyte survival in mice. (2008)
  • Author(s): Kuramochi D, et al.
  • Journal Title: Eur J Clin Invest. 38 Pages: 752-759
  • Peer Reviewed
• [Journal Article] SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. (2008)
  • Author(s): Unoki H, et al.
  • Journal Title: Nat Genet. 40 Pages: 1098-1102
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase-3 enhances the free fatty acids-induced VEGF expression in adipocytes through toll-like receptor 2. (2008)
  • Author(s): Kawamura T, et al.
  • Journal Title: Exp Biol Med 233 Pages: 1213-1221
  • Peer Reviewed
• [Journal Article] Ang II-stimulated migration of vascular smooth muscle cells is dependent on LR11 in mice. (2008)
  • Author(s): Jiang M, et al.
  • Journal Title: J Clin Invest. 118 Pages: 2733-2746
  • Peer Reviewed
• [Journal Article] Advanced glycation end products and insulin resistance. (2008)
  • Author(s): Unoki H, et al.
  • Journal Title: Curr Pharm Des. 14 Pages: 987-989
  • Peer Reviewed
• [Journal Article] Macrophages regulate tumor necrosis factor-alpha expression in adipocytes through the secretion of matrix metalloproteinase-3. (2008)
  • Author(s): Unoki H, et al.
  • Journal Title: Int J Obes 32 Pages: 902-911
  • Peer Reviewed
• [Journal Article] Low-dose GH supplementation reduces the TLR2 and TNF-alpha expressions in visceral fat. (2008)
  • Author(s): Kubota Y, et al.
  • Journal Title: Biochem Biophys Res Commun. 368 Pages: 81-87
  • Peer Reviewed
• [Journal Article] Pyridoxamine, an Inhibitor of Advanced Glycation End Product (AGE) Formation Ameliorates Insulin Resistance in Obese, Type 2 Diabetic Mice.
  • Author(s): Unoki-Kubota H, Yamagishi S, Takeuchi M, Bujo H, Saito Y.
  • Journal Title: Protein & Peptide Letters (in press)
  • Peer Reviewed
• [Presentation] KCNQ1の2型糖尿病疾患感受性に関わる分子機構 (2009)
  • Author(s): 塚田修市, 他
  • Organizer: 第24回日本糖尿病合併症学会
  • Place of Presentation: 岡山県岡山市
  • Year and Date: 2009-10-09
• [Presentation] SNPを用いた大規模ケースコントロール関連解析による糖尿病腎症疾患感受性遺伝子の同定 (2009)
  • Author(s): 卯木浩之, 他
  • Organizer: 第24回日本糖尿病合併症学会
  • Place of Presentation: 岡山県岡山市
  • Year and Date: 2009-10-09
• [Presentation] SNPを用いた大規模ケースコントロール関連解析による糖尿病性腎症疾患感受性遺伝子の探索 (2009)
  • Author(s): 卯木浩之, 他
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 東京都品川区
  • Year and Date: 2009-09-23
• [Presentation] 2型糖尿病疾患感受性遺伝子KCNQ1は膵β細胞からのインスリン分泌調節に関与する (2009)
  • Author(s): 塚田修市, 他
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 東京都品川区
  • Year and Date: 2009-09-23
• [Presentation] Identification of a New Susceptibility Gene to Diabetic Nephropathy in Japanese Subjects with Type 2 Diabetes (2009)
  • Author(s): 卯木浩之 et al.
  • Organizer: American diabetes association 69th scientific session
  • Place of Presentation: アメリカ合衆国ニューオーリンズ
  • Year and Date: 2009-06-05
• [Presentation] Effects of KCNQ1 on Glucose-Induced Insulin Secretion in Rat Pancreatic β Cells (2009)
  • Author(s): 塚田修市 et al.
  • Organizer: American diabetes association 69th scientific session
  • Place of Presentation: アメリカ合衆国ニューオーリンズ
  • Year and Date: 2009-06-05
• [Presentation] 大規模ケースコントロール相関解析による糖尿病性腎症感受性遺伝子の同定 (2009)
  • Author(s): 卯木浩之, 他
  • Organizer: 第52回日本腎臓学会学術総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2009-06-03
• [Presentation] 大規模ケースコントロール関連解析による糖尿病性腎症疾患感受性遺伝子の同定 (2009)
  • Author(s): 卯木浩之, 他
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2009-05-21
• [Presentation] SNPを用いた大規模ケースコントロール関連解析による糖尿病腎症疾患感受性遺伝子の同定 (2009)
  • Author(s): 卯木浩之、小林正明、荒木信一、馬場園哲也、川井紘一、今西政仁、岩本安彦、柏木厚典、河盛隆造、中村祐輔、前田士朗
  • Organizer: 第24回日本糖尿病合併症学会
  • Place of Presentation: 岡山
• [Presentation] SNPを用いた大規模ケースコントロール関連解析による糖尿病性腎症疾患感受性遺伝子の探索 (2009)
  • Author(s): 卯木浩之、小林正明、荒木信一、馬場園哲也、川井紘一、今西政仁、岩本安彦、柏木厚典、河盛隆造、中村祐輔、前田士朗
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 東京
• [Presentation] Identification of a New Susceptibility Gene to Diabetic Nephropathy in Japanese Subjects with Type 2 Diabetes. (2009)
  • Author(s): Unoki H, Kobayashi M, Araki S, Babazono T, Kawai K, Imanishi M, Iwamoto Y, Kashiwagi A, Kawamori R, Nakamura Y, Maeda S.
  • Organizer: American diabetes association 69th scientific session
  • Place of Presentation: New Orleans, USA
• [Presentation] 大規模ケースコントロール相関解析による糖尿病性腎症感受性遺伝子の同定 (2009)
  • Author(s): 卯木浩之、小林正明、荒木信一、馬場園哲也、川井紘一、今西政仁、岩本安彦、柏木厚典、河盛隆造、中村祐輔、前田士郎
  • Organizer: 第52回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 大規模ケースコントロール関連解析による糖尿病性腎症疾患感受性遺伝子の同定 (2009)
  • Author(s): 卯木浩之、小林正明、荒木信一、馬場園哲也、川井紘一、今西政仁、岩本安彦、柏木厚典、河盛隆造、中村祐輔、前田士郎
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
• [Presentation] Identification of a New Susceptibility Gene to Diabetic Nephropathy in Japanese Subjects with Type 2 Diabetes. (2008)
  • Author(s): Unoki H
  • Organizer: The American Society of Nephrology 41^<st> Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-04
• [Presentation] SNPを用いたゲノムワイド相関解析による2型糖尿病疾患感受性遺伝子の同定 (2008)
  • Author(s): 卯木浩之
  • Organizer: 第23回糖尿病合併症学会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-03
• [Presentation] SNPを用いたゲノムワイド相関解析による2型糖尿病疾患感受性遺伝子の探索 (2008)
  • Author(s): 卯木浩之
  • Organizer: 第53回日本人類遺伝学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-09-27
• [Presentation] Transcription Factor AP-2β Inhibits Glucose-induced Insulin Secretion in Cultured Insulin-secreting Cell Lines. (2008)
  • Author(s): Tsukada S
  • Organizer: American Diabetes Association 68^<th> Scientific Sessions
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-06-06
• [Presentation] SNPを用いたゲノムワイドケースコントロール解析による2型糖尿病疾患感受性遺伝子の同定 (2008)
  • Author(s): 卯木浩之
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-22
• [Presentation] 2型糖尿病疾患感受性遺伝子TFAP2Bは膵β細胞からのインスリン分泌調節に関与する (2008)
  • Author(s): 塚田修市
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-22
• [Presentation] Identification of a new susceptibility gene to diabetic nephropathy in Japanese subjects with type 2 diabetes. (2008)
  • Author(s): Unoki H, Kobayashi M, Araki S, Ng DP, Babazono T, Kawai K, Imanishi M, Iwamoto Y, Kashiwagi A, Kawamori R, Nakamura Y, Maeda S.
  • Organizer: The American society of nephrology 42nd Annual Meeting & Scientific Exposition
  • Place of Presentation: Philadelphia, USA
• [Presentation] SNPを用いたゲノムワイド相関解析による2型糖尿病疾患感受性遺伝子の探索 (2008)
  • Author(s): 卯木浩之、塚田修市、柏木厚典、加来浩平、門脇孝、河盛隆造、中村祐輔、前田士郎
  • Organizer: 第23回日本糖尿病合併症学会
  • Place of Presentation: 東京
• [Presentation] SNPを用いたゲノムワイド相関解析による2型糖尿病疾患感受性遺伝子の探索 (2008)
  • Author(s): 卯木浩之、塚田修市、柏木厚典、加来浩平、門脇孝、河盛隆造、中村祐輔、前田士郎
  • Organizer: 日本人類遺伝学会第53回大会
  • Place of Presentation: 横浜
• [Presentation] SNPを用いたゲノムワイドケースコントロール相関解析による2型糖尿病疾患感受性遺伝子の同定 (2008)
  • Author(s): 卯木浩之、塚田修市、柏木厚典、加来浩平、門脇孝、河盛隆造、吉川隆一、中村祐輔、前田士郎
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京