Elucidation of molecular mechanisms of insulin secretion disorders secondary to insulin resistance -study of GPR40-

• Project/Area Number: 20591094
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kyoto University
• Principal Investigator: HOSODA Kiminori Kyoto University, 医学研究科, 教授 (40271598)
• Co-Investigator(Renkei-kenkyūsha): MASUZAKI Hiroaki 京都大学, 大学院・医学研究科, 講師 (00291899) ; EBIHARA Ken 京都大学, 大学院・医学研究科, 准教授 (70362514) ; FUJIKURA Junji 京都大学, 大学院・医学研究科, 助教 (70378743) ; IWAKURA Hiroshi 京都大学, 大学院・医学研究科, 助教 (20378615) ; TOMITA Tsutomu 京都大学, 大学院・医学研究科, 非常勤講師 (50402897) ; NOGUCHI Michio 京都大学, 大学院・医学研究科, 特定研究員 (00432394)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: インスリン分泌 / GPR40 / 肥満 / コレツキーラット / 中性脂肪 / 糖尿病 / β細胞 / 膵臓 / Pdx1

Research Abstract

GPR40 is a Gq-coupled receptor, the ligand of which is middle-chain and long-chain free fatty acids. GPR40 has been reported to be expressed in pancreatic beta cells and implicated in augmentation of insulin secretion. We investigated GPR40 gene expression in pancreatic islets in genetically obese Koletsky rats. In 14-week-old Koletsky rats which shows severe obesity and sufficiency of insulin secretion, GPR40 levels were approximately 25% of those in nonobese lettermates.

Research Products

• [Journal Article] Establishment of a Novel Ghrelin-Producing Cell Line. (2010)
  • Author(s): H.Iwakura, Y.Li, H.Ariyasu, H.Hosoda, N.Kanamoto, M.Bando, G.Yamada, K.Hosoda, K.Nakao, K.Kangawa, T.Akamizu.
  • Journal Title: Endocrinology 151(6) Pages: 695-705
  • Peer Reviewed
• [Journal Article] Relevant use of Klotho in FGF19 subfamily signaling system in vivo. (2010)
  • Author(s): K.Tomiyama, R.Maeda, I.Urakawa, Y.Yamazaki, T.Tanaka, S.Ito, Y.Nabeshima, T.Tomita, S.Odori, K.Hosoda, K.Nakao, A.Imura, Y.Nabeshima
  • Journal Title: Proc Natl Acad Sci USA. 26 107(4) Pages: 1666-71
  • Peer Reviewed
• [Journal Article] Adipose Tissue-Specific Regulation of Angiotensinogen in Obese Humans and Mice : Impact of Nutritional Status and Adipocyte Hypertrophy. (2010)
  • Author(s): S.Yasue, H.Masuzaki, S.Okada, T.Ishii, C.Kozuka, T.Tanaka, J.Fujikura, K.Ebihara, K.Hosoda, A.Katsurada, N.Ohashi, M.Urushihara, H.Kobori, N.Morimoto, T.Kawazoe, M.Naitoh, M.Okada, H.Sakaue, S.Suzuki, K.Nakao.
  • Journal Title: Am J Hypertens. 23(4) Pages: 425-31
  • Peer Reviewed
• [Journal Article] Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity. (2010)
  • Author(s): S.Okada, C.Kozuka, H.Masuzaki, S.Yasue, T.Ishii-Yonemoto, T.Tanaka, Y.Yamamoto, M.Noguchi, T.Kusakabe, T.Tomita, J.Fujikura, K.Ebihara, K.Hosoda, H.Sakaue, H.Kobori, M.Ham, YS.Lee, JB.Kim, Y.Saito, K.Nakao.
  • Journal Title: Metabolism 59 Pages: 1241-1251
  • Peer Reviewed
• [Journal Article] Glucocorticoid reamplification within cells intensifies NFB and MAPK signaling and reinforces inflammation in activated preadipocytes (2010)
  • Author(s): T.Ishii-Yonemoto, H.Masuzaki, S.Yasue, S.Okada, C.Kozuka, T.Tanaka, M.Noguchi, T.Tomita, J.Fujikura, Y.Yamamoto, K.Ebihara, K.Hosoda, K.Nakao
  • Journal Title: Am J Physiol Endocrinol Metab 299(1)
  • Peer Reviewed
• [Journal Article] Establishment of a novel ghrelin-producing cell line. (2010)
  • Author(s): Iwakura H, Hosoda K, et al.
  • Journal Title: Endocrinology Volume: 151(6) Pages: 2940-5
  • Peer Reviewed
• [Journal Article] Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity. (2010)
  • Author(s): Okada S, Hosoda K, et al
  • Journal Title: Metabolism Volume: 59(9) Pages: 1241-51
  • Peer Reviewed
• [Journal Article] Glucocorticoid reamplification within cells intensifies NF-kappaB and MAPK signaling and reinforces inflammation in activated preadipocytes. (2010)
  • Author(s): Ishii-Yonemoto T, Hosoda K, et al
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 298(5)
  • Peer Reviewed
• [Journal Article] Glucocorticoid reamplification within cells intensifies NFB and MAPK signaling and reinforces inflammation in activated preadipocytes (2010)
  • Author(s): T.Ishii-Yonemoto, K.Hosoda, et al
  • Journal Title: Am J Physiol Endocrinol Metab 298(5)
  • Peer Reviewed
• [Journal Article] Clinical characteristics and efficacy of pioglitazone in a Japanese diabetic patient with an unusual type of familial partial lipodystrophy. (2009)
  • Author(s): M.Iwanishi, K.Ebihara, T.Kusakabe, W.Chen, J.Ito, H.Masuzaki, K.Hosoda, K.Nakao.
  • Journal Title: Metabolism. 58(12) Pages: 1681-7
  • Peer Reviewed
• [Journal Article] Translational research of novel hormones : lessons from animal models and rare human diseases for common human diseases. (2009)
  • Author(s): K.Nakao, A.Yasoda, K.Ebihara, K.Hosoda, M.Mukoyama.
  • Journal Title: J Mol Med. 87(10) Pages: 1029-39
  • Peer Reviewed
• [Journal Article] A mouse model of ghrelinoma exhibited activated growth hormone-insulin-like growth factor I axis and glucose intolerance. (2009)
  • Author(s): H.Iwakura, H.Ariyasu, Y.Li, N.Kanamoto, M.Bando, G.Yamada, H.Hosoda, K.Hosoda, A.Shimatsu, K.Nakao, K.Kangawa, T.Akamizu.
  • Journal Title: Am J Physiol Endocrinol Metab. 297(3)
  • Peer Reviewed
• [Journal Article] Adipogenic differentiation of human induced pluripotent stem cells : comparison with that of human embryonic stem cells (2009)
  • Author(s): D.Taura, M.D., M.Noguchi, M.Sone, K.Hosoda, E.Mori, Y.Okada, K.Takahashi, K.Homma, N.Oyamada, M.Inuzuka, T.Sonoyama, K.Ebihara, N.Tamura, H.Itoh, H.Suemori, N.Nakatsuji, H.Okano, S.Yamanaka, K.Nakao
  • Journal Title: FEBS Lett. 583(6) Pages: 1029-33
  • Peer Reviewed
• [Journal Article] Beneficial effects of leptin on glycaemic and lipid control in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and a high-fat diet. (2009)
  • Author(s): T.Kusakabe, H.Tanioka, K.Ebihara, M.Hirata, L.Miyamoto, F.Miyanaga, H.Hige, D.Aotani, T.Fujisawa, H.Masuzaki, K.Hosoda, K.Nakao.
  • Journal Title: Diabetologia. 52(4) Pages: 675-83
  • Peer Reviewed
• [Journal Article] Hypothalamic melanocortin signaling and leptin resistance--perspective of therapeutic application for obesity-diabetes syndrome. (2009)
  • Author(s): H.Masuzaki, T.Tanaka, K.Ebihara, K.Hosoda, K.Nakao.
  • Journal Title: Peptides. 30(7) Pages: 1383-6
  • Peer Reviewed
• [Journal Article] A new simple measurement system of visceral fat accumulation by bioelectrical impedance analysis (2009)
  • Author(s): T.Shiga, T.Hamaguchi, Y.Oshima, H.Kanai, M Hirata, K.Hosoda, K, Nakao
  • Journal Title: IFMBE 25 Pages: 338-341
  • Peer Reviewed
• [Journal Article] Index of the systemic balance of end products of glucocorticoid metabolism in fresh urine from humans. Its potential usefulness in the evaluation of obesity-related diseases. (2009)
  • Author(s): N.Kobayashi, H.Masuzaki, T.Tanaka, S.Yasue, T.Ishii, T.Tomita, T.Miyawaki, T.Komeda, Y.Fukuda, T.Kusakabe, M.Noguchi, J.Fujikura, K.Ebihara, M.Hirata, K.Hosoda, N.Satoh, M.Nakajima, Y.Okabayashi, T.S.Sato, K.Nakao.
  • Journal Title: Obesity Research and Clinical Practice 3(2) Pages: 53-63
  • Peer Reviewed
• [Journal Article] Translational research of novel hormones : lessons from animal models and rare human diseases for common human diseases (2009)
  • Author(s): K.Nakao, K.Hosoda, et al
  • Journal Title: J Mol Med. 87(10) Pages: 1029-1039
  • Peer Reviewed
• [Journal Article] A mouse model of ghrelinoma exhibited activated growth hormone-insulin-like growth factor I axis and glucose intolerance (2009)
  • Author(s): H.Iwakura, K.Hosoda, et al
  • Journal Title: Am J Physiol Endocrinol Metab. 297(3)
  • Peer Reviewed
• [Journal Article] Adipogenic differentiation of human induced pluripotent stem cells : comparison with that of human embryonic stem cells (2009)
  • Author(s): D. Taura, K. Hosoda, et al
  • Journal Title: FEBS Lett. 583(6) Pages: 1029-33
  • Peer Reviewed
• [Journal Article] Beneficial effects of leptin on glycaemic and lipid control in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and a high-fat diet. (2009)
  • Author(s): T. Kusakabe, K. Hosoda, et al
  • Journal Title: Diabetologia 52(4) Pages: 675-83
  • Peer Reviewed
• [Journal Article] Index of the systemic balance of end products of glucocorticoid metabolism in fresh urine from humans. Its potential usefulness in the evaluation of obesity-related diseases. (2009)
  • Author(s): N. Kobayashi, K. Hosoda, et al
  • Journal Title: Obesity Research and Clinical Practice
  • Peer Reviewed
• [Journal Article] Establishment of a novel neuroblastoma mouse model. (2008)
  • Author(s): H.Iwakura, H.Ariyasu, N.Kanamoto, K.Hosoda, K.Nakao, K.Kangawa, T.Akamizu.
  • Journal Title: Int J Oncol.Dec 33(6) Pages: 1195-9
  • Peer Reviewed
• [Journal Article] Establishment of a novel neuroblastoma mouse model. (2008)
  • Author(s): H. Iwakura, K. Hosoda, et al
  • Journal Title: Int J Oncol. 33(6) Pages: 1195-9
  • Peer Reviewed
• [Presentation] 新規のG蛋白共役型-脂肪酸受容体GPR40の遺伝子肥満モデルの膵島での発現調節 (2010)
  • Author(s): 冨田努, 細田公則, 小鳥真司, 藤倉純二, 岩倉浩, 野口倫生, 日下部徹, 海老原健, 益崎裕章, 中尾一和
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 群馬県前橋市
• [Presentation] Gene expression of a G protein-coupled receptor, GPR119, in humans (2010)
  • Author(s): T.Tomita, K.Hosoda, S.Odori, J.Fujikura, K.Nakao
  • Organizer: 11^<th> International Congress on Obesity
  • Place of Presentation: Stockholm, Sweden
• [Presentation] 膵β細胞に高発現し,中・長鎖の遊離脂肪酸をリガンドとするG蛋白共役型-脂質受容体GPR40の遺伝性肥満モデルの膵島での発現調節 (2010)
  • Author(s): 冨田努, 細田公則, 小鳥真司, 藤倉純二, 岩倉浩, 野口倫生, 日下部徹, 海老原健, 益崎裕章, 中尾一和
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
• [Presentation] Gene Expression of a G Protein-coupled Receptor, GPR40, in Pancreatic Islets of a Genetically Obese Rat Mode (2010)
  • Author(s): T.Tomita, K.Hosoda, S.Odori, J.Fujikura, H.Iwakura, M.Noguchi, T.Kusakabe, K.Ebihara, H.Masuzaki, K.Nakao
  • Organizer: Keystone Symposia
  • Place of Presentation: Whistler, British Columbia, Canada
• [Presentation] Decreased gene expression of a G protein-coupled fatty acid receptor GPR40 in pancreatic islets of Koletsky rats (2010)
  • Author(s): T.Tomita, K.Hosoda, S.Odori, J.Fujikura, H.Iwakura, M.Noguchi, E.Mori, M.Naito, T.Kusakabe, K.Ebihara, H.Masuzaki, K.Nakao
  • Organizer: 14th International Congress of Endocrinology (ICE2010)
  • Place of Presentation: Kyoto, Japan
• [Presentation] 膵β細胞に高発現し, 中・長鎖の遊離脂肪酸をリガンドとするG蛋白共役型-脂質受容体GPR40の遺伝性肥満モデルの膵島での発現調節 (2010)
  • Author(s): 冨田努, 細田公則, 他
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
• [Presentation] 新規のG蛋白共役型受容体GPR119の臨床的意義 : ヒトにおける遺伝子発現の検討 (2009)
  • Author(s): 小鳥真司, 細田公則, その, 他
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 群馬
  • Year and Date: 2009-04-25
• [Presentation] G蛋白共役型受容体40(GPR40)の肥満・糖代謝異常における意義の検討 (2009)
  • Author(s): 冨田努, 細田公則, その他
  • Organizer: 第82回 日本内分泌学会学術総会
  • Place of Presentation: 群馬
  • Year and Date: 2009-04-23
• [Presentation] G蛋白共役型受容体40(GPR40)の肥満・糖代謝異常における意義の検討 (2009)
  • Author(s): 冨田努, 細田公則, 小鳥真司, 藤倉純二, 岩倉浩, 野口倫生, 森栄作, 内藤雅喜, 海老原健, 益崎裕章, 中尾一和
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 群馬
• [Presentation] G蛋白共役型受容体40(GPR40)の肥満・糖代謝異常の発症・進展における意義の検討 (2008)
  • Author(s): 冨田努, 細田公則, 小鳥真司, 藤倉純二, 岩倉浩, 野口倫生, 森栄作, 海老原健, 平田雅一, 益崎裕章, 中尾一和
  • Organizer: 第29回日本肥満学会
  • Place of Presentation: 大分
• [Presentation] G蛋白共役型-脂肪酸受容体GPR40の糖尿病でのインスリン分泌調整異常における病態生理的意義の検討 (2008)
  • Author(s): 冨田努, 細田公則, 小鳥真司, 藤倉純二, 岩倉浩, 野口倫生, 海老原健, 平田雅一, 益崎裕章, 中尾一和
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
• [Presentation] 肥満を基盤とする耐糖能異常の発症・進展におけるG蛋白共役型脂肪酸受容体GPR40の意義の検討-遺伝性肥満Koletskyラットの膵島でのGPR40遺伝子発現- (2008)
  • Author(s): 冨田努, 細田公則, 小鳥真司, 藤倉純二, 岩倉浩, 野口倫生, 海老原健, 平田雅一, 益崎裕章, 中尾一和
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
• [Presentation] Decreased Gene Expression of a Membrane-Bound Fatty Acid Receptor, GPR40, in Pancreatic Islets in Koletsky Rats, a Genetically Obese Model with Dysregulated Insulin Secretion (2008)
  • Author(s): T.Tomita, K.Hosoda, S.Odori, J.Fujikura, H.Iwakura, M.Noguchi, K.Ebihara, M.Hirata, H.Masuzaki, K.Nako
  • Organizer: Keystone Symposia (Islet and Beta Cell Biology)
  • Place of Presentation: Snowbird, Utah
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/jpn/research/diabetes.html
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/index-jp.html