Elucidation of the role of GIP in pancreatic glucagon secretion.

• Project/Area Number: 25461345
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The Tazuke Kofukai (2014-2015); Kyoto University (2013)
• Principal Investigator: HAMASAKI Akihiro 公益財団法人田附興風会, 医学研究所第3研究部, 部長 (40456900)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: グルカゴン / インクレチン / GIP / 膵島 / 肥満 / GLP-1 / インスリン / インクレチン作用 / 糖尿病 / 2型糖尿病 / 膵β細胞

Outline of Final Research Achievements

We performed basic experiments and clinical studies to elucidate the role of glucose-dependent insulinotropic polypeptide (GIP) in modification of glucagon secretion in diabetes and obesity. We generated and analysed tissue-specific GIP receptor knock-out mice in basic study. We also investigated the relation between glucagon secretion and incretin secretion, and clarified that GIP affected the glucagon secretion especially in postprandial state.

Research Products

• [Journal Article] Enteral supplement enriched with glutamine, fiber, and oligosaccharide modulates incretin and glucagon-like peptide-2 secretion. (2015)
  • Author(s): Joo E., Muraoka A., Hamasaki A., Harada N., Yamane S., Kondo Y., Suzuki K., Nasteska D., Shibue K., Harada T., Iwasaki K., Tsuji H., Shide K., Inagaki N.
  • Journal Title: J Diabetes Investig. Volume: 6 Issue: 3 Pages: 302-308
  • DOI: 10.1111/jdi.12289
  • Peer Reviewed / Open Access
• [Journal Article] Fatty acid binding protein 5 (FABP5) regulates diet-induced obesity (DIO) via GIP secretion from enteroendocrine K-cells in response to fat ingestion. (2015)
  • Author(s): Shibue, K., Yamane, S., Harada, N., Hamasaki, A., Suzuki, K., Joo, E., Iwasaki, K., Nasteska, D., Harada, T., Hayashi, Y., Adachi, Y., Owada, Y., Takayanagi, R. and Inagaki, N.
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 308 Issue: 7 Pages: 583-591
  • DOI: 10.1152/ajpendo.00543.2014
  • Peer Reviewed / Open Access
• [Journal Article] Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K-cells of upper small intestine and has a critical role in GIP secretion after fat ingestion. (2015)
  • Author(s): Iwasaki K, Harada N, Sasaki K, Yamane S, Iida K, Suzuki K, Hamasaki A, Joo E, Nasteska D, Shibue K, Harada T, Hashimoto T, Asakawa Y, Hirasawa A, Inagaki N.
  • Journal Title: Endocrinology Volume: 156 Issue: 3 Pages: 837-837
  • DOI: 10.1210/en.2014-1653
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Chronic reduction of GIP secretion alleviates obesity and insulin resistance under high fat diet condition. (2014)
  • Author(s): Nasteska, D., Harada, N., Suzuki, K., Yamane, S., Hamasaki, A., Joo, E., Mori, K., Shibue, K., Harada, T., Inagaki, N.
  • Journal Title: Diabetes Volume: 63 Issue: 7 Pages: 2332-2343
  • DOI: 10.2337/db13-1563
  • NAID: 120005458283
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet-induced obesity. (2013)
  • Author(s): Suzuki K, Harada N, Yamane S, Nakamura Y, Sasaki K, Nasteska D, Joo E, Shibue K, Harada T, Hamasaki A, Toyoda K, Nagashima K, Inagaki N.
  • Journal Title: J Biol Chem. Volume: 288 Issue: 3 Pages: 1929-1938
  • DOI: 10.1074/jbc.m112.423137
  • NAID: 120005373090
  • Peer Reviewed
• [Journal Article] Enteral supplement enriched with glutamine, fiber, and oligosaccharide attenuates experimental colitis in mice (2013)
  • Author(s): Joo E, Yamane S, Hamasaki A, Harada N, Matsunaga T, Muraoka A, Suzuki K, Nasteska D, Fukushima T, Hayashi T, Tsuji H, Shide K, Tsuda K, Inagaki N
  • Journal Title: Nutrition Volume: 29(3):549-55 Issue: 3 Pages: 549-555
  • DOI: 10.1016/j.nut.2012.09.007
  • NAID: 120005242568
  • Peer Reviewed
• [Journal Article] A new equation to estimate basal energy expenditure of patients with diabetes. (2012)
  • Author(s): Ikeda K, Fujimoto S, Goto M, Yamada C, Hamasaki A, Ida M, Nagashima K, Shide K, Kawamura T, Inagaki N.
  • Journal Title: Clin Nutr. Volume: 未定 Issue: 5 Pages: 777-782
  • DOI: 10.1016/j.clnu.2012.11.017
  • NAID: 120005324918
  • Peer Reviewed
• [Presentation] Possible proteolyzaation of circulating betatrophin in human serum (2015)
  • Author(s): Tokumoto S, Hamamoto Y, Yamaguchi E, Okamura E, Honjo S, Hamasaki A
  • Organizer: International Diabetes Federation 2015 World Congress
  • Place of Presentation: Vancouver（Canada）
  • Year and Date: 2015-11-30
  • Int'l Joint Research
• [Presentation] Early phase glucagon secretion associated with GIP reflects preferentially glucose disposal after oral glucose loading (2015)
  • Author(s): Hamasaki A, Muraoka A, Harada N, Yamane S, Joo E, Suzuki K, Shibue K, Harada T, Iwasaki K, Inagaki N
  • Organizer: 7th AASD Scientific Meeting
  • Place of Presentation: Hong Kong（China）
  • Year and Date: 2015-10-21
  • Int'l Joint Research
• [Presentation] 脂肪酸結合タンパク5（FABP5）は胆汁の作用を介したK細胞における脂肪誘導性GIP分泌の制御に関与する (2015)
  • Author(s): 渋江公尊、山根俊介、原田範雄、濱崎暁洋、鈴木和代、城尾恵里奈、岩崎可南子、ダニエラナステスカ、原田貴成、安達泰弘、大和田祐二、高柳涼一、稲垣暢也
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 海峡メッセ下関（山口県下関市）
  • Year and Date: 2015-05-21
• [Presentation] インクレチン効果と脂肪酸分画の関連についての検討 (2015)
  • Author(s): 濱崎暁洋、村岡 敦、原田範雄、山根俊介、城尾恵里奈、鈴木和代、渋江公尊、原田貴成、岩崎可南子、稲垣暢也
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: ホテルニューオータニ（東京都千代田区）
  • Year and Date: 2015-04-23
• [Presentation] 肥満時のインクレチン効果修飾因子としても脂肪酸分画の検討 (2015)
  • Author(s): 村岡 敦、濱崎暁洋、原田範雄、山根俊介、城尾恵里奈、鈴木和代、渋江公尊、原田貴成、山本泰三、稲垣暢也
  • Organizer: 第112回日本内科学会総会・講演会
  • Place of Presentation: 京都国際会議場（京都市左京区）
  • Year and Date: 2015-04-10
• [Presentation] シンポジウム 明日から使えるインクレチン分泌・作用と栄養 ―糖尿病患者におけるインクレチン効果 (2015)
  • Author(s): 濱崎暁洋
  • Organizer: 第18回日本病態栄養学会年次学術集会
  • Place of Presentation: 京都国際会議場（京都市左京区）
  • Year and Date: 2015-01-10 – 2015-01-11
  • Invited
• [Presentation] Glucose-dependent Insulinotropic Polypeptide (GIP) Is Involved in Inappropriate Glucagon Secretion in Response to Oral Glucose Loading in Type 2 Diabetes (2014)
  • Author(s): Hamasaki A, Muraoka A, Harada N, Yamane S, Joo E, Suzuki K, Kondo Y, Shibue K, Harada T, Iwasaki K, Inagaki N
  • Organizer: 10th IDF-WPR CONGRESS 2014 | 6th AASD Scientific Meeting
  • Place of Presentation: Singapore
  • Year and Date: 2014-11-21 – 2014-11-24
• [Presentation] Relationship between Fatty Acid Profile and Incretin Effect in Normal Glucose Tolerance (2014)
  • Author(s): Muraoka A, Hamasaki A, Harada N, Yamane S, Joo E, Suzuki K, Konodo Y, Shibue K, Harada T, Iwasaki K, Inagaki N
  • Organizer: 10th IDF-WPR CONGRESS 2014 | 6th AASD Scientific Meeting
  • Place of Presentation: Singapore
  • Year and Date: 2014-11-21 – 2014-11-24
• [Presentation] Inhibition of GIP receptor signalling in adipose tissue reduces insulin resistance in high fat diet-induced obesity (2014)
  • Author(s): E. Joo, N. Harada, T. Fukushima, A. Hamasaki, S. Yamane, K. Iwasaki, D. Nasteska, K. Shibue, T. Harada, K. Suzuki, N. Inagaki
  • Organizer: 50th European association for the study of diabetes annual meeting
  • Place of Presentation: Vienna
  • Year and Date: 2014-09-15 – 2014-09-19
• [Presentation] 肥満軽減におけるインクレチン効果改善についての検討 (2014)
  • Author(s): 濱崎暁洋、村岡 敦、原田範雄、山根俊介、鈴木和代、城尾恵里奈、ナステスカダニエラ、池田香織、近藤八重子、渋江公尊、原田貴成、森可南子、藤原雄太、長嶋一昭、稲垣暢也
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡国際会議場（福岡市博多区）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 糖負荷後グルカゴン分泌抑制に対するインクレチン分泌・効果の検討 (2013)
  • Author(s): 浜崎暁洋、原田範雄、村岡敦、山根俊介、鈴木和代、Nasteska Daniela、城尾恵里奈、佐々木香月、近藤八重子、菱澤方洋、渋江公尊、原田貴成、森可南子、稲垣暢也
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] インクレチン効果と糖負荷後遊離脂肪酸の関連についての検討 (2013)
  • Author(s): 村岡敦、浜崎暁洋、原田範雄、山根俊介、鈴木和代、Nasteska Daniela、城尾恵里奈、佐々木香月、近藤八重子、菱澤方洋、渋江公尊、原田貴成、森可南子、稲垣暢也
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] Lowering GIP secretion is beneficial for reducing obesity and insulin resistance without impairing glucose tolerance and osteogenesis (2013)
  • Author(s): Daniela Nasteska, Norio Harada, Shunsuke Yamane, Kazuyo Suzuki, Akihiro Hamasaki, Erina Joo, Kazuki Sasaki, Atsushi Muraoka, Kimitaka Shibue, Takanari Harada, Yaeko Kondo, Nobuya Inagaki
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] K細胞に高発現する転写因子Regulatory factor X 6(Rfx6) はGIP遺伝子発現ならびに、高脂肪食肥満下のGIP分泌亢進に関与する (2013)
  • Author(s): 鈴木和代、原田範雄、山根俊介、中村靖彦、佐々木香月、Nasteska Daniela、森可南子、城尾恵里奈、渋江公尊、原田貴成、浜崎暁洋、稲垣暢也
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] Distribution of fatty acid binding receptors in GIP-secreting K cells in the small intestine
  • Author(s): K.Mori,N.Harada,K.Suzuki,S.Yamane,A.Hamasaki,K.Sasaki,D.Nasteska,E.Joo,K.Shibue,T.Harada,N.Inagaki
  • Organizer: 49th EASD Annual Meeting
  • Place of Presentation: barcelona, Spain
• [Presentation] Inhibition of GIP Receptor signaling in adipose tissue improves insulin sensitivity under high fat diet-induced obesity
  • Author(s): E.Joo,N.Harada,A.Hamasaki,K.Mori,T.Fukushima,K.Shibue,D.Nasteska,K.Suzuki,T.Harada,S.Yamane,T.Hayashi,K.Tsuda,N.Inagaki
  • Organizer: 5th AASD
  • Place of Presentation: Seoul, Korea