Taste receptor : a new therapeutic target for obesity and diabetes

• Project/Area Number: 20689034
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Kyushu University
• Principal Investigator: SHIGEMURA Noriatsu Kyushu University, 歯学研究院, 准教授 (40336079)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥22,880,000 (Direct Cost: ¥17,600,000、Indirect Cost: ¥5,280,000); Fiscal Year 2010: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2009: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2008: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
• Keywords: 味覚 / うま味 / 遺伝子多型性 / 受容体 / 臓器 / ヒト / 肥満

Research Abstract

Umami taste is elicited by L-glutamate, and is thought to be one of five basic taste qualities that plays a key role in intake of amino acids. A heterodimer of a G protein coupled receptor, T1R1 and T1R3, is proposed to function as its receptor. However, little is known about single nucleotide polymorphisms (SNP) in the genes and its potential links with individual differences in umami sensitivity. Here we investigated the association between recognition thresholds for umami substances and genetic variations in human T1R1 and T1R3, and the functions of T1R1/T1R3 variants using a heterologous expression system. Our study demonstrated that the T1R1-372Thr creates a more sensitive umami receptor than -372Ala, while T1R3-757Cys creates a less sensitive one than -757Arg for umami substances, and showed a strong correlation between the recognition thresholds and in vitro dose-response relationships. These results in human studies support the propositions that a T1R1/T1R3 heterodimer acts as an umami receptor, and that genetic variation in this heterodimer directly affects umami taste sensitivity.

Research Products

• [Journal Article] Taste preference for fatty acids is mediated by GPR40andGPR120. (2010)
  • Author(s): Cartoni C, Yasumatsu K, Ohkuri T, Shigemura N, Yoshida R, Godinot N, le Coutre J, Ninomiya Y, Damak S.
  • Journal Title: JNeurosci. 30(25) Pages: 8376-8382
  • Peer Reviewed
• [Journal Article] Modulation of sweet taste sensitivity by orexigenic and anorexigenic factors. (2010)
  • Author(s): Jyotaki M, Shigemura N, Ninomiya Y.
  • Journal Title: Endocr J. 57(6) Pages: 467-475
  • NAID: 10029584967
  • Peer Reviewed
• [Journal Article] New frontiers ingut nutrient sensor research: nutrient sensors in the gastrointestinal tract: modulation of sweet taste sensitivity by leptin. (2010)
  • Author(s): Horio N, Jyotaki M, Yoshida R, Sanematsu K, Shigemura N, Ninomiya Y.
  • Journal Title: J Pharmacol Sci. 112(1) Pages: 8-12
  • Peer Reviewed
• [Journal Article] Endocannabinoids selectively enhance sweet taste. (2010)
  • Author(s): Yoshida R, Ohkuri T, Jyotaki M, Yasuo T, Horio N, Yasumatsu K, Sanematsu K, Shigemura N, Yamamoto T, Margolskee RF, Ninomiya Y.
  • Journal Title: Proc Natl Acad Sci USA. 107(2) Pages: 935-939
  • Peer Reviewed
• [Journal Article] Taste preference for fatty acids is mediated by GPR40 and GPR120. (2010)
  • Author(s): Cartoni C, Yasumatsu K, Ohkuri T, Shigemura N, Yoshida R, Godinot N, le Coutre J, Ninomiya Y, Damak S.
  • Journal Title: J Neurosci. Volume: 30 Pages: 8376-82
  • Peer Reviewed
• [Journal Article] Modulation of sweet taste sensitivity by orexigenic and anorexigenic factors. (2010)
  • Author(s): Jyotaki M, Shigemura N, Ninomiya Y.
  • Journal Title: Endocr J. Volume: 57 Pages: 467-75
  • NAID: 10029584967
  • Peer Reviewed
• [Journal Article] New frontiers in gut nutrient sensor research : nutrient sensors in the gastrointestinal tract : modulation of sweet taste sensitivity by leptin. (2010)
  • Author(s): Norio N, Jyotaki M, Yoshida R, Sanematsu K, Shigemura N, Ninomiya Y.
  • Journal Title: J Pharmacol Sci. 112(1) Pages: 8-12
  • NAID: 10027908348
  • Peer Reviewed
• [Journal Article] Genetically-increased taste cell population with G(alpha)-gustduc in-coupled sweet receptors is associated with increase of gurmarin-sensitive taste nerve fibers in mice. (2009)
  • Author(s): Yasumatsu K, Ohkuri T, Sanematsu K, Shigemura N, Katsukawa H, Sako N, Ninomiya Y.
  • Journal Title: BMC Neurosci. 10 Pages: 152-152
  • Peer Reviewed
• [Journal Article] Genetic and molecular basis of individual differences in human umami taste perception. (2009)
  • Author(s): Shigemura N, Shirosaki S, Sanematsu K, Yoshida R, Ninomiya Y.
  • Journal Title: PLoS One. 4(8)
  • Peer Reviewed
• [Journal Article] Modulation and transmission of sweet taste information for energy homeostasis. (2009)
  • Author(s): Sanematsu K, Horio N, Murata Y, Yoshida R, Ohkuri T, Shigemura N, Ninomiya Y.
  • Journal Title: Ann N Y Acad Sci. 1170 Pages: 102-106
  • Peer Reviewed
• [Journal Article] Multiple receptor systems for umami taste in mice. (2009)
  • Author(s): Yoshida R, Yasumatsu K, Shirosaki S, Jyotaki M, Horio N, Murata Y, Shigemura N, Nakashima K, Ninomiya Y.
  • Journal Title: Ann N Y Acad Sci. 1170 Pages: 51-54
  • Peer Reviewed
• [Journal Article] Variation in umami perception and in candidate genes for the umami receptor in mice and humans. (2009)
  • Author(s): Shigemura N, Shirosaki S, Ohkuri T, Sanematsu K, Islam AA, Ogiwara Y, Kawai M, Yoshida R, Ninomiya Y.
  • Journal Title: Am J Clin Nutr. 90(3)
  • Peer Reviewed
• [Journal Article] Discrimination of taste qualities among mouse fungiform taste bud cells. (2009)
  • Author(s): Yoshida R, Miyauchi A, Yasuo T, Jyotaki M, Murata Y, Yasumatsu K, Shigemura N, Yanagawa Y, Obata K, Ueno H, Margolskee RF, Ninomiya Y.
  • Journal Title: J Physiol. 587(Pt18) Pages: 4425-4439
  • Peer Reviewed
• [Journal Article] Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. (2009)
  • Author(s): Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Kojima I.
  • Journal Title: PLoS One. 4(4)
  • Peer Reviewed
• [Journal Article] NaCl responsive taste cells in the mouse fungiform taste buds. (2009)
  • Author(s): Yoshida R, Horio N, Murata Y, Yasumatsu K, Shigemura N, Ninomiya Y.
  • Journal Title: Neuroscience. 159(2) Pages: 795-803
  • Peer Reviewed
• [Journal Article] Endocannabinoids selectively enhance sweet taste. (2009)
  • Author(s): Yoshida R, Ohkuri T, Jyotaki M, Yasuo T, Horio N, Yasumatsu K, Sanematsu K, Shigemura N, Yamamoto T, Margolskee RF, Ninomiya Y.
  • Journal Title: Proc Natl Acad Sci USA. 107(2) Pages: 935-9
  • Peer Reviewed
• [Journal Article] Genetically-increased taste cell population with G(alpha)-gustducin-coupled sweet receptors is associated with increase of gurmarin-sensitive taste nerve fibers in mice. (2009)
  • Author(s): Yasumatsu K, Ohkuri T, Sanematsu K, Shigemura N, Katsukawa H, Sako N, Ninomiya Y.
  • Journal Title: BMC Neurosci. 10 Pages: 152-152
  • Peer Reviewed
• [Journal Article] Modulation and transmission of sweet taste information for energy home ostasis. (2009)
  • Author(s): Sanematsu K, Horio N, Murata Y, Yoshida R, Ohkuri T, Shigemura N, Ninomiya Y.
  • Journal Title: Ann N Y Acad Sci. 1170 Pages: 102-6
  • Peer Reviewed
• [Journal Article] Discrimination of taste qualities among mouse fungiform taste bud cells. (2009)
  • Author(s): Yoshida R, Miyauchi A, Yasuo T, Jyotaki M, Murata Y, Yasumatsu K, Shigemura N, Yanagawa Y, Obata K, Ueno H, Margolskee RF, Ninomiya Y.
  • Journal Title: J physiol. 587 Pages: 4425-39
  • Peer Reviewed
• [Journal Article] ヒトT1R1/T1R3に対するギムネマ酸の相互作用部位の同定 (2009)
  • Author(s): 實松敬介、重村憲徳、上瀧雅史、中村誠司、井本敏明、二ノ宮裕三
  • Journal Title: 日本味と匂学会誌 16(3) Pages: 287-90
  • Peer Reviewed
• [Journal Article] マウス味細胞におけるGABAの機能解析 (2009)
  • Author(s): 安尾敏明、吉田竜介、堀尾奈央、重村憲徳、二ノ宮裕三
  • Journal Title: 日本味と匂学会誌 16(3) Pages: 323-6
  • NAID: 110007568727
  • Peer Reviewed
• [Journal Article] Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion (2009)
  • Author(s): Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Koiima I.
  • Journal Title: PLoS ONE 4
  • Peer Reviewed
• [Journal Article] NaC1 responsive taste cells in the mouse fungiform taste buds (2009)
  • Author(s): Yoshida R, Horio N, Murata Y, Yasumatsu K, Shigemura N, Ninomiya Y.
  • Journal Title: Neuroscience 159 Pages: 795-803
  • Peer Reviewed
• [Journal Article] Diurnal variation of human sweet taste recognition thresholds is correlated with plasma leptin levels. (2008)
  • Author(s): Nakamura Y, Sanematsu K, Ohta R, Shirosaki S, Koyano K, Nonaka K, Shigemura N, Ninomiya Y.
  • Journal Title: Diabetes. 57(10) Pages: 2661-2665
  • Peer Reviewed
• [Journal Article] Diurnal variation of human sweet taste recognition thresholds is correlated with plasma leptin levels. (2008)
  • Author(s): Nakamura Y, Sanematsu K, Ohta R, Shirosaki S, Koyano K, Nonaka K, Shigemura N, Ninomiya Y.
  • Journal Title: Diabetes 57 Pages: 2661-5
  • Peer Reviewed
• [Journal Article] Gurmarin sensitivity of sweet taste responses is associated with co-expression patterns of T1r2, T1r3, and gustducin (2008)
  • Author(s): Shigemura N, Nakao K, Yasuo T, Murata Y, Yasumatsu K, Nakashima A, KatsukawaH, SakoN, Ninomiya Y.
  • Journal Title: Biochem Biophys Res Commun. 367 Pages: 356-63
  • Peer Reviewed
• [Journal Article] Amiloride-sensitive NaC1 taste responses are associated with genetic variation of ENaC alpha-subunit in mice (2008)
  • Author(s): Shigemura N, Ohkuri T, Sadamitsu C, Yasumatsu K, Yoshida R, Beauchamp GK, Bachmanov AA, Ninomiya Y.
  • Journal Title: Am J Physiol Regul Integr Comp Physiol. 294
  • Peer Reviewed
• [Journal Article] mGluRアンタゴニスト混合うま味溶液に対するTIR3-KOおよびc57BL/6マウスの行動学的解析 (2008)
  • Author(s): 城崎慎也、川東由利子、中島清人、重村憲徳、安松啓子、吉田竜介、Robert F-Margolskee、ニノ宮裕三
  • Journal Title: 日本味と匂学会誌 15 Pages: 293-6
  • Peer Reviewed
• [Journal Article] トリテルペン配糖体とヒト甘味受容体hTIR2/hTIR3の相互作用 (2008)
  • Author(s): 實松敬介、重村憲徳、中村誠司、井元敏明、ニノ宮裕三
  • Journal Title: 日本味と匂学会誌 15 Pages: 297-300
  • Peer Reviewed
• [Journal Article] グルタミン酸受容体アンタゴニスト添加うま味物質で嫌悪条件付けそたマウスの各種味物質に対する般化 (2008)
  • Author(s): 中島清人、勝川秀夫、城崎慎也、重村憲徳、ニノ宮裕三
  • Journal Title: 日本味と匂学会誌 15 Pages: 653-6
  • Peer Reviewed
• [Presentation] マウス味細胞の味応答に対するGABAの影響 (2010)
  • Author(s): 安尾敏明、吉田竜介、重村憲徳、柳川右千夫、二ノ宮裕三
  • Organizer: 第52回歯科基礎医学会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-21
• [Presentation] Single nucleotide polymorphisms(SNPs)in taste sensor genes and perceptual diversity. (2010)
  • Author(s): Shigemura N, Ogiwara Y, Sanematsu K, Kawai M, Yoshida R, Ninomiya Y.
  • Organizer: 87th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Iwate, Japan
  • Year and Date: 2010-05-21
• [Presentation] Single nucleotide polymorphisms (SNP) in taste sensor genes and perceptual diversity. (2010)
  • Author(s): Shigemura N, Shirosaki S, Sanematsu K, Ogiwara Y, Kawai M, Yoshida R, Ninomiya Y
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-21
• [Presentation] ヒトうま味感受性の多様性における遺伝・分子学的基盤 (2010)
  • Author(s): 重村憲徳、城崎慎也、實松敬介、吉田竜介、二ノ宮裕三
  • Organizer: 第8回口腔医科学フロンティア学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2010-03-06
• [Presentation] ヒトうま味感受性の多様性における遺伝・分子学的基盤 (2010)
  • Author(s): 重村憲徳
  • Organizer: 第8回口腔医科学フロンティア
  • Place of Presentation: 福岡
  • Year and Date: 2010-03-06
• [Presentation] 味覚と肥満 (2009)
  • Author(s): 重村憲徳
  • Organizer: 日本咀嚼学会第20回記念学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2009-10-03
• [Presentation] Functional expression study of TAS1R1/TAS1R3 receptor variants associated with individual differences in human umami taste sensitivity (2009)
  • Author(s): Shigemura N, et al.
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-27
• [Presentation] Functional analysis of TAS1R1/TAS1R3 umami rtaste eceptor variants. (2009)
  • Author(s): Shigemura N, Shirosaki S, Sanematsu K, Ogiwara Y, Kawai M, Yoshida R, Ninomiya Y.
  • Organizer: 32th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2009-09-17
• [Presentation] 味覚センサーの特性と多様性:うま味感受性の個体差と受容体遺伝子多型 (2009)
  • Author(s): 二ノ宮裕三、重村憲徳
  • Organizer: 第51回歯科基礎医学会
  • Place of Presentation: 新潟
  • Year and Date: 2009-09-10
• [Presentation] ヒトうま味感受性の多様性における遺伝・分子学的基盤 (2009)
  • Author(s): 重村憲徳
  • Organizer: 日本味と匂学会第43回大会
  • Place of Presentation: 旭川
  • Year and Date: 2009-09-03
• [Presentation] Functional expression study of TAS1R1/TAS1R3 receptor variants associated with individual differences in human umami taste sensitivity. (2009)
  • Author(s): Shigemura N, Shirosaki S, Sanematsu K, Ogiwara Y, Kawai M, Yoshida R, Ninomiya Y.
  • Organizer: 36th Congress of the International Union of Physiological Sciences
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2009-07-31
• [Presentation] Functional expression study of TAS1R1/TAS1R3 receptor variants associated with individual differences in human umami taste sensitivity (2009)
  • Author(s): Shigemura N, et al.
  • Organizer: 第36回国際生理学会世界大会
  • Place of Presentation: 京都
  • Year and Date: 2009-07-31
• [Presentation] 口腔科学の最前線 (2009)
  • Author(s): 重村憲徳
  • Organizer: 第2回東京アンチエイジングアカデミー
  • Place of Presentation: 東京
  • Year and Date: 2009-05-27
• [Presentation] Genitic and Molecular Basis of Indivisual Differences in human Umami Taste Perception (2009)
  • Author(s): Shigemura N, Shirosaki S, Sanematsu K, Ogiwara Y, Kawai M, Yoshida R, Ninomiya Y.
  • Organizer: 31th Annual Meeting of the Association for Chemoreception Sciences
  • Place of Presentation: Sarasota, USA
  • Year and Date: 2009-04-24
• [Presentation] Genetic and molecular basis of individual differences in human umami taste perception (2009)
  • Author(s): Shigemura N, et al.
  • Organizer: 第31回The Association for Chemoreception Sciences (AChemS)
  • Place of Presentation: サラソタ(USA)
  • Year and Date: 2009-04-24
• [Presentation] Relationship between individual differences in umami taste sensitivity and genetic variations of T1r1 and T1r3 in human (2008)
  • Author(s): Shigemura N, Shirosaki S, Sanematsu K, Shahidal AA Islam, Ogiwara Y, Kawai M, Yoshida R, Ninomiya Y.
  • Organizer: 6th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2008-12-06
• [Presentation] Relationship between individual differences in umami taste sensitivity and genetic variations of Tlrl and T1r3 in human (2008)
  • Author(s): Shigemura N, et.al.
  • Organizer: 第6回国際シンポジウム「味覚嗅覚の分子神経機構」
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2008-12-06
• [Presentation] ヒトうま味感受性の多様性とうま味受容体遺伝子多型性との相関 (2008)
  • Author(s): 重村憲徳、イスラムアブ、城崎慎也、實松敬介、荻原葉子、河合美佐子、吉田竜介、二ノ宮裕三
  • Organizer: 日本味と匂学会第42回大会
  • Place of Presentation: 富山
  • Year and Date: 2008-09-18
• [Presentation] Variation in umami perception and its receptor candidate genes in humans (2008)
  • Author(s): Shigemura N., et.al.
  • Organizer: IGTC Ikeda Symposium
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2008-09-12
• [Presentation] Relationship between individual differences in umami taste sensitivity and genetic variations of T1rs and mGluRs in human (2008)
  • Author(s): Shigemura N
  • Organizer: 100th anniversary symposium of umami discovery, International Glutamate Technical Committee
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2008-09-11
• [Presentation] Genetic alteration of gurmarin sensitivity is associated with formation of both receptor and neural system for sweet taste in mice (2008)
  • Author(s): Shigemura N., et.al.
  • Organizer: 第15回ISOT・第30回AChemS
  • Place of Presentation: サンフランシスコ(USA)
  • Year and Date: 2008-07-24
• [Presentation] Genetic alteration of gurmarin sensitivity is associated with formation of both receptor and neural system for sweet taste in mice. (2008)
  • Author(s): Shigemura N, Yasuo T, Shirosaki S, Yasumatsu K, Katsukawa H, Imoto T, Sako N, Ninomiya Y.
  • Organizer: International Symposium on Olfaction and Taste
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-07-22
• [Book] 医学のあゆみ「味覚受容体の構造と機能の多様性」233(9) 290 (2010)
  • Author(s): 重村憲徳、二ノ宮裕三
  • Publisher: 医歯薬出版株式会社
• [Book] 実験医学「内因性カンナビノイドの甘味増強作用」 28(9) 136 (2010)
  • Author(s): 田竜介、大栗弾宏、重村憲徳、二ノ宮裕三
  • Publisher: 羊土社
• [Book] 医学のあゆみ:最新Gタンパク質共役型受容体:味覚受容体の構造と機能の多様性 (2010)
  • Author(s): 重村憲徳、二ノ宮裕三
  • Total Pages: 6
  • Publisher: 医歯薬出版株式会社
• [Book] オンラインジャーナルTeamApproachスペシャル特集:糖尿病と歯科疾患の密接な関係「肥満糖尿病と味覚」 (2009)
  • Author(s): 重村憲徳、二ノ宮裕三
  • Publisher: ネイチャージャパン株式会社
  • URL: http://www.team-approach.net/myaccount/login.php?forward=/tokushu/article.php?id=50
• [Book] Team Approach連載:糖尿病と歯周疾患の密接な関係「肥満糖尿病と味覚」 (2009)
  • Author(s): 重村憲徳、二ノ宮裕三
  • Publisher: NPGネイチャーアジア・パシフィックネイチャージャパン株式会社
• [Book] ANTI-AGINGMEDICINE「味覚の新知見」vol.4-5 136 (2008)
  • Author(s): 重村憲徳、二ノ宮裕三
  • Publisher: メディカルビュー社
• [Book] アンチエイジング医学の基礎と臨床:「味覚とアンチエイジング」 (2008)
  • Author(s): 重村憲徳、二ノ宮裕三
  • Publisher: メディカルビュー社
• [Book] アンチエイジング医学の基礎と臨床 : 味覚とアンチエイジング (2008)
  • Author(s): 重村憲徳、ニノ宮裕三
  • Total Pages: 455
  • Publisher: メディカルビュー社
• [Book] ANTI-AGINGMEDICINEvo1. 4-5 : 味覚の新知見 (2008)
  • Author(s): 重村憲徳、ニノ宮裕三
  • Total Pages: 135
  • Publisher: メディカルビュー社
• [Remarks] ホームページ等
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