Regulation mechanism of nutrient assimilation and exocrine system which is achieved by the carbohydrate-recognition of pancreatic enzymes

• Project/Area Number: 22570111
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Ochanomizu University
• Principal Investigator: OGAWA Haruko お茶の水女子大学, 大学院・人間文化創成科学研究科, 教授 (90143700)
• Co-Investigator(Renkei-kenkyūsha): KAWASAKI Nana 国立医薬品食品衛生研究所, 生物薬品部, 部長 (20186167)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2012: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 膵臓酵素 / 糖鎖認識 / 糖質消化 / 糖質吸収 / 外分泌調節 / 糖尿病 / α-アミラーゼの糖結合性 / トリプシノーゲンの糖結合性 / リパーゼの糖結合性 / トリプシンの糖結合性 / 血糖値恒常性 / DPP4 / SGLT1 / 糖鎖認識の意義 / 消化・吸収 / 糖代謝 / Na^+-Glc共輸送体1(SGLT1) / α-アミラーゼ / Na+-Glc共輸送体1(SGLT1)

Research Abstract

We found novel carbohydrate-binding activities of pancreatic enzymes; -amylase, trypsinogen/trypsin, and lipase, etc. The carbohydrate-binding sites of bovine trypsinogen and trypsin were identified by cocrystallization with Me -GalNAc, and X-ray crystallography. Expression, purification, and refolding methods of recombinant human pancreatic lipase were established for the first time using Escherichia coli. The interaction between -amylase and N-glycans in the BBM activated starch degradation to produce much more Glc on one hand, while suppressing a sharp increase in Glc absorption on the other. Therefore, the carbohydrate recognition of α-amylase was shown to playa key role in regulating Glc assimilation to maintain blood homeostasis in the intestine.

Research Products

• [Journal Article] Functional Regulation of Sugar Assimilation by N-Glycan-specific Interaction of Pancreatic α-Amylase with Glycoproteins of Duodenal Brush Border Membrane. (2012)
  • Author(s): Asanuma-Date K, Hirano Y, LeNa, Sano K, Kawasaki N, Hashii N, Hiruta Y, Nakayama K, Umemura M, Ishikawa K, Sakagami H, Ogawa H.
  • Journal Title: J. Biol. Chem. Volume: 287 Issue: 27 Pages: 23104-18
  • DOI: 10.1074/jbc.m111.314658
  • Peer Reviewed
• [Journal Article] Novel anti-HIV-1 activity produced by conjugating unsulfated dextran with polyL-lysine (2012)
  • Author(s): Nakamura K
  • Journal Title: Antiviral Res Volume: 94 Issue: 1 Pages: 89-97
  • DOI: 10.1016/j.antiviral.2012.02.011
  • Peer Reviewed
• [Journal Article] Matrix Restructuring During Liver Regeneration is Regulated by Glycosylation of the Matrix Glycoprotein Vitronectin (2012)
  • Author(s): Ogawa, H., Sano, K., Sobukawa, N., Asanuma-Date, K
  • Journal Title: Liver regeneration Volume: Baptista, P. ed Pages: 79-98
  • Peer Reviewed
• [Journal Article] Matrix Restructuring During Liver Regeneration is Regulated by Glycosylation of the Matrix Glycoprotein Vitronectin. (2012)
  • Author(s): Haruko Ogawa, Kotone Sano, Naomi Sobukawa and Kimie Asanuma-Date
  • Journal Title: "Liver regeneration" Baptista, P. ed., InTech Volume: 5 Pages: 79-98
  • DOI: 10.5772/45636
  • ISBN: 9789535106227
  • Peer Reviewed
• [Journal Article] Glycosylation Changes in Matrix Glycoproteins Regulate the Matrix Restructuring during Liver Regeneration Liver Regeneration (2012)
  • Author(s): Ogawa H., Sano, K., Sobukawa, N.
  • Journal Title: Liver regeneration Baptista P., ed., In Tech-Open Access Publisher Volume: (In press)
  • Peer Reviewed
• [Journal Article] Usefulness of specific antibodies to immobilize pyridylaminated N-glycans for solid-phase interaction analyses (2011)
  • Author(s): Le, N., Kato, M., Kubo, H., Hirashima, Y., Sakagami, H., Ogawa H
  • Journal Title: Nat Sci. Rept. Ochanomizu Univ. Tokyo Volume: 61 Pages: 31-45
  • NAID: 120002835833
  • URL: http://hdl.handle.net/10083/49657
  • Peer Reviewed
• [Journal Article] Usefulness of specific antibodies to immobilize pyridylaminated N-glycans for solid-phase interaction analyses. (2011)
  • Author(s): Na Le, Mari Kato, Haruko Ogawa
  • Journal Title: Nat.Sci.Rept.Ochanomizu Univ.,Tokyo Volume: 61 Pages: 31-45
  • NAID: 120002835833
  • Peer Reviewed
• [Journal Article] Survival of Hepatic Stellate Cell during Liver Regeneration is Regulated by the Changes in Glycosylation of Rat Vitronectin especially the Decreased Hypersialylation (2010)
  • Author(s): Sano, K., Miyamoto, Y., Kawasaki, N., Hashii, N., Itoh, S., Yokoyama, M., Sato, C., Kitajima, K., Ogawa, H
  • Journal Title: J. Biol. Chem Volume: 285 Issue: 23 Pages: 17301-17309
  • DOI: 10.1074/jbc.m109.077016
  • Peer Reviewed
• [Journal Article] Survival signals of hepatic stellate cells in liver regeneration are regulated by glycosylation changes in rat vitronectin, especially decreased sialylation. (2010)
  • Author(s): Kotone Sano, Yasunori Miyamoto, Nana Kawasaki, Noritaka Hashii, Satsuki Itoh, Misaki Murase, Kimie Date, Mild Yokoyama, Chihiro Sato, Ken Kitajima, Haruko Ogawa
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 17301-17309
  • Peer Reviewed
• [Journal Article] 細胞外マトリックス分子の糖鎖による肝再生の制御 (2010)
  • Author(s): 伊達公恵、佐野琴音、小川温子
  • Journal Title: 化学工業 Volume: 12・902 Pages: 902-910
• [Presentation] Another method of controlling Glc assimilation at high α-amylase concentrations inintestine through N-glycan-specific interactions (2013)
  • Author(s): K. Date, N. Kawasaki, N. Hashii, H.Sakagami, H. Ogawa
  • Organizer: Int. Symp. Glycoconjugates (Glyco22)
  • Place of Presentation: Dalian, China.
  • Year and Date: 2013-06-27
• [Presentation] 膵α-アミラーゼと腸内糖鎖リガンドとの結合を介する糖吸収調節機構の発見 (2012)
  • Author(s): 伊達公恵、川崎ナナ、橋井則貴、蛭田葉子、坂上ひろみ、小川温子
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
  • Year and Date: 2012-12-16
• [Presentation] ヒト膵リパーゼの大腸菌発現と糖結合性およびその脂質分解活性への影響 (2012)
  • Author(s): 富田千尋、楢舘里奈、樋上智子、相川京子、小川温子
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
  • Year and Date: 2012-12-15
• [Presentation] 膵リパーゼの糖結合性と複合糖質による活性への影響 (2012)
  • Author(s): 富田千尋、楢舘里奈、樋上智子、相川京子、小川温子
  • Organizer: GlycoTOKYO2012
  • Place of Presentation: 東京慶応大学薬学部
  • Year and Date: 2012-11-17
• [Presentation] Carbohydrate-specific interaction of mammalian pancreatic α-amylases with glycoproteins on intestinal mucosa regulates their functions (2012)
  • Author(s): K. Date, N. Kawasaki, N. Hashii, Y.Hiruta, H. Sakagami, H. Ogawa
  • Organizer: ASMB/SFG Joint meeting 2012
  • Place of Presentation: San Diego, USA
  • Year and Date: 2012-11-12
• [Presentation] ウシトリプシノーゲンの糖特異的相互作用による活性化調節の構造的基盤 (2012)
  • Author(s): 三橋佳奈、斉藤泉、和田有沙、坂上ひろみ、白井剛、今野美智子、小川温子
  • Organizer: 第31回日本糖質学会年会
  • Place of Presentation: 鹿児島国際会議場
  • Year and Date: 2012-09-20
• [Presentation] Ogawa Pancreatic Trypsinogen Is Controlled by Sugar-specific Interaction (2012)
  • Author(s): K. Mitsuhashi, I. Saito, A. Wada, H.Sakagami, M. Konno, T. Shirai, H
  • Organizer: EWU, JWU, OU Joint Symposium 2012
  • Place of Presentation: Seoul, Korea.
  • Year and Date: 2012-07-15
• [Presentation] OgawaExpression, purification and refolding of recombinant human pancreatic lipase in Escherichia coli (2012)
  • Author(s): H. Tomita, R. Naradate, T. Higam, K.Aikawa, H
  • Organizer: EWU, JWU, OU Joint Symposium 2012
  • Place of Presentation: Seoul, Korea.
  • Year and Date: 2012-07-15
• [Presentation] 膵α-アミラーゼの糖タンパク質糖鎖結合性は腸内の糖質消化・吸収を高次調節する (2012)
  • Author(s): 伊達公恵、楽娜、川崎ナナ、橋井則貴、蛭田葉子、坂上ひろみ、小川温子
  • Organizer: 平成24年度日本生化学会関東支部例会
  • Place of Presentation: 群馬大学医学部、群馬
  • Year and Date: 2012-06-23
• [Presentation] ウシトリプシノーゲンの活性化の糖特異的相互作用による調節 (2012)
  • Author(s): 三橋佳奈、斉藤泉、和田有沙、白井剛、今野美智子、小川温子
  • Organizer: 平成24年度日本生化学会関東支部例会
  • Place of Presentation: 群馬大学医学部、群馬
  • Year and Date: 2012-06-23
• [Presentation] ヒト膵リパーゼの大腸菌における発現、精製とリフォールディング (2012)
  • Author(s): 富田千尋、楢舘里奈、樋上智子、相川京子、小川温子
  • Organizer: 第12回日本蛋白質科学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2012-05-22
• [Presentation] 膵酵素の糖結合性と膵臓外分泌顆粒における膵酵素間の相互作用解析 (2012)
  • Author(s): 三ツ木礼子、大崎加奈恵、伊達公恵、小川温子
  • Organizer: 第12回日本蛋白質科学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2012-05-22
• [Presentation] 膵α-アミラーゼと腸内糖鎖リガンドとの結合を介する糖吸収調節機構の発見 (2012)
  • Author(s): K. Date, N. Kawasaki, N. Hashii, Y. Hiruta, H. Sakagami, H. Ogawa.
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡、福岡
• [Presentation] シュードプロテオグリカンPLL-Dexの抗HIV-1活性 Anti-HIV-1 activity of pseudoproteoglycan prepared by conjugating unsulfated dextran with poly-L-lysine (2012)
  • Author(s): 狩野文枝、中村公亮、大槻貴博、森治代、星野洪郎、Ariful Hoque、大上厚志、棚元憲一、牛島廣治、坂上ひろみ、小川温子
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡、福岡
• [Presentation] ヒト膵リパーゼの大腸菌発現と糖結合性およびその脂質分解活性への影響、Expression of Pancreatic Lipase and studies on the Carbohydrate-binding and Lipolytic Activity (2012)
  • Author(s): 富田千尋、楢舘里奈、樋上智子、相川京子、小川温子
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡、福岡
• [Presentation] Characterization of The Anti-HIV-1 Mechanism of a Pseudoproteoglycan Produced by Conjugating Unsulfated Dextran with Poly-L-lysine (2012)
  • Author(s): Haruko Ogawa,Fumie Kano, Takahiro Otsuki, Hiroo Hoshino, Kosuke Nakamura, Haruyo Mori, Hiromi Sakagami
  • Organizer: ASMB/SFG Joint meeting 2012
  • Place of Presentation: San Diego, USA
• [Presentation] Carbohydrate-specific interaction of mammalian pancreatic α-amylases with glycoproteins on intestinal mucosa regulates their functions. (2012)
  • Author(s): K. Date, N. Kawasaki, N. Hashii, H Sakagami, H. Ogawa.
  • Organizer: ASMB/SFG Joint meeting 2012
  • Place of Presentation: San Diego, USA
• [Presentation] Novel anti-HIV-1 activity produced by conjugating unsulfated dextran with poly-L-lysine and characterization of the unique antiviral mechanism (2012)
  • Author(s): F. Kano, T. Otsuki, K.Nakamura, H. Mori, H. Hoshino, H. Sakagami, H. Ogawa
  • Organizer: ASMB/SFG Joint meeting 2012
  • Place of Presentation: San Diego, USA
• [Presentation] ウシトリプシノーゲンの糖特異的相互作用による活性化調節の構造的基盤 (2012)
  • Author(s): 三橋佳奈、斉藤泉、和田有沙、坂上ひろみ、白石剛、今野美智子、小川温子
  • Organizer: 第３１回日本糖質学会年会
  • Place of Presentation: 鹿児島
• [Presentation] 膵臓外分泌における顆粒内の糖鎖とプロテアーゼチモーゲンとの相互作用 (2012)
  • Author(s): 三橋佳奈、斉藤泉、和田有沙、坂上ひろみ、白石剛、今野美智子、小川温子
  • Organizer: 第３１回日本糖質学会年会
  • Place of Presentation: 鹿児島
• [Presentation] ヒト膵リパーゼの大腸菌発現とその糖結合性および脂質分解、Expression of Pancreatic Lipase and its carbohydrate-binding and Lipolytic Activity (2012)
  • Author(s): 富田千尋、楢舘里奈、樋上智子、相川京子、小川温子
  • Organizer: 第３１回日本糖質学会年会
  • Place of Presentation: 鹿児島
• [Presentation] Pancreatic Trypsinogen Is Controlled by Sugar-specific Interactinon (2012)
  • Author(s): K. Mitsuhashi, I. Saitho, A. Wada, H. Sakagami, M. Konno, T. Shirai, H. Ogawa
  • Organizer: EWU, JWU, OU Joint Symposium 2012
  • Place of Presentation: Seoul
• [Presentation] Expression, purification and refolding of recombinant human pancreatic lipase in Escherichia coli (2012)
  • Author(s): 富田千尋、楢舘里奈、樋上智子、相川京子、小川温子
  • Organizer: EWU, JWU, OU Joint Symposium 2012
  • Place of Presentation: Seoul
• [Presentation] Fc Regions of Mammalian Immunoglobulins Have Carbohydrate-Recognition Activities (2011)
  • Author(s): N.Le, Y.Hirashima, M.Kato, K.Sano, H.Sakagami, H.Ogawa
  • Organizer: 3^<rd> The 3rd ACGG Conference
  • Place of Presentation: China, Shanghai
  • Year and Date: 2011-12-28
• [Presentation] Functional Regulation of Sugar Assimilation by Newly-Identified Receptors for Pancreatic α-Amylase in Duodenal Brush Border Membrane via Carbohydrate-specific Interactions (2011)
  • Author(s): Date K., Kawasaki N., Hashii N., Ito S., Le N., Hirano Y., Ogawa H.
  • Organizer: Joint Research Symposium 2011, JWU, Ochanomizu and Ehwa woman university
  • Place of Presentation: 韓国・Seoul
  • Year and Date: 2011-12-21
• [Presentation] 小川温子膵臓外分泌顆粒形成と膵臓酵素の持つpH依存的糖鎖結合性の関係 (2011)
  • Author(s): 三ツ木礼子、大崎加奈恵、伊達公恵
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-14
• [Presentation] Novel anti-HIV-1 mechanism of pseudoproteoglycan, conjyugate of unsulfiated glycans with poly-L-lysine, is different from that of sulfated polysaccharides (2011)
  • Author(s): Kano F., Nakamura K., Hoshino H., Otsuki T., Oue A., Shimisu N., Nakamura T., Sakagami H., Ogawa H.
  • Organizer: 21^<st> International Symposium on Glycoconjyugates
  • Place of Presentation: オーストリア・ウィーン
  • Year and Date: 2011-08-26
• [Presentation] The New Receptors for Pancreatic α-Amylase Controls The Blood Glucose Concentration via Carbohydrate-Specific Interaction (2011)
  • Author(s): Date K., Kawasaki N., Hashii N., Ito S., Le N., Hirano Y., Ogawa H.
  • Organizer: 21^<st> International Symposium on Glycoconjyugates
  • Place of Presentation: オーストリア・ウィーン
  • Year and Date: 2011-08-26
• [Presentation] Newly identified receptors for pancreatic α-amylase controls blood glucose concentration via carbohydrate-specific interactions (2011)
  • Author(s): Kimie Date; Nana Kawasaki; Noritaka Hashii; Na Le; Yuki Hirano; Haruko Ogawa
  • Organizer: 21th Int. Symp. Glycoconjugates (Glyco21)
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2011-08-23
• [Presentation] Roles of glycosylation of vitronectin in the inflammatory changes of liver (2011)
  • Author(s): Kotone Sano, Yasunori Miyamoto, Mio Tanabe, Nana Kawasaki, Noritaka. Hashii, Satsuki. Itoh, Sadako Yamada, Haruko Ogawa
  • Organizer: 3^<rd> Japan-Netherlands Glycobiology Symposium
  • Place of Presentation: 日本・名古屋(招待講演)
  • Year and Date: 2011-07-09
• [Presentation] 細胞外マトリックス分子の糖鎖による肝再生の制御 (2010)
  • Author(s): 小川温子
  • Organizer: 第4回 多糖の未来フォーラム
  • Place of Presentation: 東京医科歯科大学歯学部特別講堂
  • Year and Date: 2010-11-04
• [Presentation] Novel regulation of glucose productionand assimilation by carbohydrate- specific interaction between pancreatic α-amylase and brush border glycoproteins in duodenum (2010)
  • Author(s): K. Date; N. Kawasaki; N. Hashii; S. Ito; N. Le; Y. Hirano; H. Ogawa
  • Organizer: 25th Int. Carbohydrate Symp (ICS2010)
  • Place of Presentation: Makuhari, Japan
  • Year and Date: 2010-08-03
• [Presentation] 膵リパーゼの糖結合性と複合糖質による活性への影響
  • Author(s): 富田千尋、楢舘里奈、樋上智子、相川京子、小川温子
  • Organizer: GlycoTOKYO2012
  • Place of Presentation: 東京
• [Presentation] 膵α-アミラーゼの糖タンパク質糖鎖結合性は腸内の糖質消化・吸収を高次調節する
  • Author(s): 伊達 公恵、楽 娜、川崎 ナナ、橋井 則貴、蛭田 葉子、坂上 ひろみ、小川 温子
  • Organizer: 平成24年度 日本生化学会関東支部例会
  • Place of Presentation: 群馬大学医学部、群馬
• [Presentation] シュードプロテオグリカン、PLL-Dex の HIV-1 感染抑制機構に関する研究
  • Author(s): 狩野文枝、中村公亮、坂上ひろみ、小川温子
  • Organizer: 平成24年度 日本生化学会関東支部例会
  • Place of Presentation: 群馬大学医学部、群馬
• [Presentation] ウシトリプシノーゲン活性化の糖特異的相互作用による調節
  • Author(s): 三橋佳奈、斉藤泉、和田有沙、白石剛、今野美智子、小川温子
  • Organizer: 平成24年度 日本生化学会関東支部例会
  • Place of Presentation: 群馬大学医学部、群馬
• [Presentation] 抗体Fc 領域が持つ糖結合活性の分子シミューレーション
  • Author(s): 楽娜、平島友里恵、加藤真利、小川温子
  • Organizer: 平成24年度 日本生化学会関東支部例会
  • Place of Presentation: 群馬大学医学部、群馬
• [Presentation] ヒト膵リパーゼの大腸菌における発現、精製とリフォールディング、Expression, purification and refolding of recombinant human pancreatic lipase in Escherichia coli
  • Author(s): 富田千尋、楢舘里奈、樋上智子、相川京子、小川温子
  • Organizer: 第１２回日本蛋白質科学会年会
  • Place of Presentation: 名古屋
• [Book] 日刊工業新聞2012年3月29日掲載「お茶の水女子大、抗HIV薬が効かなくなったとき新治療薬を作りやすい化合物開発」 (2012)
  • Author(s): 冨井哲雄
  • Total Pages: 1
  • Publisher: 日刊工業新聞社
• [Book] 化学-最新のトピックス.糖鎖によるがん克服への挑戦-今なぜ糖鎖が重要か.化学 (2011)
  • Author(s): 佐野琴音,小川温子
  • Publisher: 化学同人刊
  • URL: http://www.fujisan.co.jp/product/366/b/620179/
• [Book] 化学 (雑誌) 5月号 「糖鎖によるがん克服への挑戦」 (2011)
  • Author(s): 佐野琴音、小川温子
  • Total Pages: 108
  • Publisher: 化学同人
• [Book] 小川温子細胞外マトリックス分子の糖鎖による肝再生の制御.化学工業
  • Author(s): 伊達公恵,佐野琴音
  • Publisher: 化学工業社刊
  • URL: http://iss.ndl.go.jp/books/R000000004-I10911380-00
• [Remarks]
  • URL: http://www.sci.ocha.ac.jp/chemHP/labos/ogawaHP/files/Page477.htm
• [Remarks] お茶の水女子大学 理学部化学科 小川研究室
  • URL: http://www.sci.ocha.ac.jp/chemHP/labos/ogawaHP/index.htm
• [Remarks]
  • URL: http://www.sci.ocha.ac.jp/chemHP/labos/ogawaHP/index.htm
• [Patent(Industrial Property Rights)] 組み替えヒト膵リパーゼの調製方法 (2012)
  • Inventor(s): 小川温子、相川京子、富田千尋、楢舘里奈、樋上智子
  • Industrial Property Rights Holder: 国立大学法人お茶の水女子大学
  • Industrial Property Number: 2012-263442
  • Filing Date: 2012-11-30
  • Overseas
• [Patent(Industrial Property Rights)] 組み換えヒト膵臓リパーゼの調製方法 (2012)
  • Inventor(s): 小川温子、相川京子、富田千尋、楢舘里奈、樋上智子
  • Industrial Property Rights Holder: 小川温子、相川京子、富田千尋、楢舘里奈、樋上智子
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-263442
  • Filing Date: 2012-11-30
• [Patent(Industrial Property Rights)] シュードプロテオグリカンおよびその用途 (2011)
  • Inventor(s): 小川温子
  • Industrial Property Rights Holder: 国立大学法人お茶の水女子大学
  • Filing Date: 2011-06-30
  • Overseas
• [Patent(Industrial Property Rights)] 公開特許シュードプロテオグリカンおよびその用途 (2004)
  • Inventor(s): 小川温子
  • Industrial Property Rights Holder: 国立大学法人お茶の水女子大学
  • Filing Date: 2004-03-31
  • Acquisition Date: 2011-06-17