Important Role of Angiotensin Receptor Subtype in Adipocyte Differentiation and Insulin Resistance

• Project/Area Number: 18590992
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Ehime University
• Principal Investigator: IWAI Masaru Ehime University, 大学院・医学系研究科, 准教授 (00184854)
• Co-Investigator(Kenkyū-buntansha): HORIGUCHI Masatsugu 愛媛大学, 大学院・医学系研究科, 教授 (40150338)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: 血管病態学 / アンジオテンシン受容体 / 脂肪細胞 / 細胞分化 / AT1受容体ブロッカー / 動脈硬化 / インスリン感受性 / アディポサイトカイン / 転写調節因子 / 分化 / アンジオテンシン / AT1受容体 / AT2受容体 / インスリン抵抗性 / 糖尿病 / 炎症反応 / 脂肪組織 / 脂質代謝 / レニン-アンジオテンシン系 / 受容体 / メタボリックシンドローム

Research Abstract

本研究において、脂肪組織に対するアンジオテンシンII受容体サブタイプの役割について、我々の用いた動脈硬化モデルマウスにおいて、AT1受容体刺激が、糖取り込み低下をはじめ、脂肪重量増加、脂肪細胞大型化、脂肪細胞分化抑制、血中脂質上昇などの変化を引き起こすのに対し、もう一つの主要サブタイプであるAT2受容体刺激は、糖取り込み増加、脂肪細胞分化促進、脂肪細胞小型化、脂肪細胞重量低下、血中脂質低下などAT1受容体に拮抗的に働くことが示された。これらの結果から、将来AT2受容体アゴニストがメタボリック症候群の治療に新たな一面を切り開く可能性がある。

Research Products

• [Journal Article] Continuous Activation of Renin-Angiotensin System Impairs Cognitive Function in Renin/Angiotensinogen Transgenic Mice (2009)
  • Author(s): Inaba S, Iwai M, Furuno M, Tomono Y, Kanno H, Senba I, Okayama H, Mogi M, Higaki J, Horiuchi M
  • Journal Title: Hypertension 53(2) Pages: 356-362
  • Peer Reviewed
• [Journal Article] Prevention of Vascular Injury by Combination of an AT1 Receptor Prevention of Vascular Injury by Combination of an AT1 Receptor Blocker, Olmesartan, with Various Calcium Antagonists (2009)
  • Author(s): Inaba S, Iwai M, Tomono Y, Senba I, Furuno M, Kanno H, Okayama H, Mogi M, Higaki J, Horiuchi M
  • Journal Title: Am J Hypertens 22(2) Pages: 145-150
  • Peer Reviewed
• [Journal Article] Exaggeration of focal cerebral ischemia in transgenic mice carrying human renin and human angiotensinogen genes (2009)
  • Author(s): Inaba S, Iwai M, Tomono Y, Senba I, Furuno M, Kanno H, Okayama H, Mogi M, Higaki J, Horiuchi M
  • Journal Title: Stroke 40 Pages: 597-603
  • Peer Reviewed
• [Journal Article] AT2 Receptor Deficiency Attenuates Adipocyte Differentiation and Decreases Adipocyte Number in Atherosclerotic Mice (2009)
  • Author(s): Iwai M, Tomono Y, et al.
  • Journal Title: American Journal of Hypertension (印刷中)
  • Peer Reviewed
• [Journal Article] Continuous Activation of Renin-Angiotensin System Impairs Cognitive Function in Renin/Angiotensinogen Transgenic Mice (2009)
  • Author(s): Inaba S, Iwai M, et al.
  • Journal Title: Hypertension 22 Pages: 145-150
  • Peer Reviewed
• [Journal Article] Exaggeration of focal cerebral ischemia in transgenic mice carrying human renin and human angiotensinogen genes (2009)
  • Author(s): Inaba S, Iwai M, et al.
  • Journal Title: Stroke 40 Pages: 597-603
  • Peer Reviewed
• [Journal Article] Deletion of angiotensin II type 2 receptor attenuates protective effects of bone marrow stromal cell treatment on ischemia reperfusion brain injury in mice (2008)
  • Author(s): Iwanami J, Mogi M, Li J-M, Tsukuda K, Min L-J, Sakata A, Fujita T, Iwai M, Horiuchi M
  • Journal Title: Stroke 39 Pages: 22554-22559
  • Peer Reviewed
• [Journal Article] Temporary pretreatment with the angiotensin II type 1 receptor blocker, valsartan, prevents ischemic brain damage through an increase in capillary density (2008)
  • Author(s): Li JM, Mogi M, Iwanami J, Min LJ, Tsukuda K, Sakata A, Fujita T, Iwai M, Horiuchi M
  • Journal Title: Stroke 39 Pages: 2029-2036
  • Peer Reviewed
• [Journal Article] Telmisartan prevented cognitive decline partly due to PPAR-gamma activation (2008)
  • Author(s): Mogi M, Li J-M, Tsukuda K, Iwanami J, Min L-J, Sakata A, Fujita T. Iwai M, Horiuchi M
  • Journal Title: Biochem Biophys Res Commun 375 Pages: 446-449
  • Peer Reviewed
• [Journal Article] Attenuation of focal brain ischemia by telmisartan, an angiotensin II type 1 receptor blocker, in atherosclerotic apolipoprotein E-deficient mice (2008)
  • Author(s): Iwai M, Inaba S, Tomono Y, Kanno H, Iwanami J, Mogi M, Horiuchi M
  • Journal Title: Hypertens Res. 31 Pages: 161-168
  • NAID: 10021261491
  • Peer Reviewed
• [Journal Article] Akt-FOXO3a signaling affects human endothelial progenitor cell differentiation (2008)
  • Author(s): Mogi M, Walsh K, Iwai M, Horiuchi M
  • Journal Title: Hypertens Res. 31 Pages: 153-159
  • NAID: 10021261462
  • Peer Reviewed
• [Journal Article] Diabetes-associated cognitive impairment is improved by a calcium channel blocker, nifedipine (2008)
  • Author(s): Tsukuda K, Mogi M, Li JM, Iwanami J, Min LJ, Sakata A, Fujita T, Iwai M, Horiuchi M
  • Journal Title: Hypertension 51 Pages: 528-533
  • Peer Reviewed
• [Journal Article] Blockade of AT(1) Receptor Improves Adipocyte Differentiation in Atherosclerotic and Diabetic Models (2008)
  • Author(s): Tomono Y, Iwai M, Inaba S, Mogi M, Horiuchi M.
  • Journal Title: Am J Hypertens 21 Pages: 206-212
  • Peer Reviewed
• [Journal Article] Blockade of ATl Receptor Improves Adipocyte Differentiation in Atherosclerotic and Diabetic Models (2008)
  • Author(s): Tomono Y, Iwai, M, et. al.
  • Journal Title: American Journal of Hypertension 21 Pages: 206-212
  • Peer Reviewed
• [Journal Article] Inhibition of cognitive decline in mice fed a high-salt and cholesterol diet by the angiotensin receptor blocker, olmesartan (2007)
  • Author(s): Mogi M, Tsukuda K, Li JM, Iwanami J, Min LJ, Sakata A, Fujita T, Iwai M, Horiuchi M.
  • Journal Title: Neuropharmacology 53 Pages: 899-905
  • Peer Reviewed
• [Journal Article] Amelioration of Cognitive Impairment in the Type-2 Diabetic Mouse by the Angiotensin II Type-1 Receptor Blocker Candesartan (2007)
  • Author(s): Tsukuda K, Mogi M, Li JM, Iwanami J, Min LJ, Sakata A, Fujita T, Iwai M, Horiuchi M
  • Journal Title: Hypertension 50 Pages: 1099-1105
  • Peer Reviewed
• [Journal Article] Attenuation of Monocyte Chemoattractant Protein-1 Expression Via Inhibition of Nuclear Factor-kappaB Activity in Inflammatory Vascular Injury (2007)
  • Author(s): Gao X, Iwai M, Inaba S, Tomono Y, Kanno H, Mogi M, Horiuchi M
  • Journal Title: Am J Hypertens 20 Pages: 1170-1175
  • Peer Reviewed
• [Journal Article] Cross-talk between aldosterone and angiotensin II in vascular smooth muscle cell senescence (2007)
  • Author(s): Min LJ, Mogi M, Iwanami J, Li JM, Sakata A, Fujita T, Tsukuda K, Iwai M,Horiuchi M.
  • Journal Title: Cardiovasc Res. 76 Pages: 506-516
  • Peer Reviewed
• [Journal Article] Pretreatment with eplerenone reduces stroke volume in mouse middle cerebral artery occlusion model (2007)
  • Author(s): Iwanami J, Mogi M, Okamoto S, Gao X-Y, Li J-M, Min L-J, Ide A, Tsukuda K, Iwai M, Horiuchi M.
  • Journal Title: European Journal of Pharmacology 566 Pages: 153-159
  • Peer Reviewed
• [Journal Article] TAK-536, a New AT1 Receptor Blocker, Improves Glucose Intolerance and Adipocyte Differentiation (2007)
  • Author(s): Iwai M, Chen R, Imura Y, Horiuchi M.
  • Journal Title: Am J Hypertens 20 Pages: 579-586
  • Peer Reviewed
• [Journal Article] Attenuation of Monocyte Chemoattractant Protein-1 Expression Via Inhibition of Nuclear Factor-kappaB Activity in Inflammatory Vascular Injury (2007)
  • Author(s): Gao X, Iwai M, et. al.
  • Journal Title: American Journal of Hypertension 20 Pages: 1170-1175
  • Peer Reviewed
• [Journal Article] TAK-536,a New ATI Receptor Blocker,Improves Glucose Intolerance and Adipocyte Differentiation (2007)
  • Author(s): Iwai M, Chen R, et. al.
  • Journal Title: American Journal of Hypertension 20 Pages: 579-586
  • Peer Reviewed
• [Journal Article] Calcium channel blocker, azelnidipine, reduces glucose intolerance in diabetic mice via different mechanism to angiotensin receptor blocker, olmesartan. (2006)
  • Author(s): Iwai, M., Li, H-S., Chen, R., Shiuchi, T., Wu, L., Min, L-J., Li, J-M., et al.
  • Journal Title: J Pharmacol Exp Ther 319 Pages: 1081-1087
• [Journal Article] Attenuation of inflammatory vascular remodeling by angiotensin II type 1 receptor-associated protein. (2006)
  • Author(s): Oshita, A., Iwai, M., Chen, R., Ide, A., Okumura, M., Fukunaga, S., et al.
  • Journal Title: Hypertension 48 Pages: 671-676
• [Journal Article] Comparison of inhibitory action of candesartan and enalapril on brain ischemia through inhibition of oxidative stress. (2006)
  • Author(s): Hamai, M., Iwai, M., Ide, A., Tomochika, H., Tomono, Y., et al.
  • Journal Title: Neuropharmacology 51 Pages: 822-828
• [Journal Article] The calcium-channel blocker, azelnidipine, enhanced the inhibitory action of AT1 receptor blockade on ischemic brain damage. (2006)
  • Author(s): Iwai, M., Chen, R., Ide, A., Iwanami, J., Tomochika, H., et al.
  • Journal Title: Journal of Hypertension 24 Pages: 2023-2031
• [Journal Article] Eplerenone with valsartan effectively reduces atherosclerotic lesion by attenuation of oxidative stress and inflammation. (2006)
  • Author(s): Suzuki, J., Iwai, M., Mogi, M., Oshita, A., Yoshii, T., Higaki, J., et al.
  • Journal Title: Arterioscler Thromb Vasc Biol 26 Pages: 917-921
• [Journal Article] Regression of atherosclerosis by amlodipine via anti-inflammatory and anti-oxidative stress actions. (2006)
  • Author(s): Yoshii, T., Iwai, M., Li, Z., Chen, R., Ide, A., Fukunaga, S., et al.
  • Journal Title: Hypertension Res 29 Pages: 457-466
  • NAID: 10018347364
• [Journal Article] Nifedipine inhibited angiotensin II-induced MCP-1 expression : involvement of IkB kinase and NF-kB-inducing kinase. (2006)
  • Author(s): Wu, L., Iwai, M., Li, Z., Li, J-M., Mogi, M., Horiuchi, M
  • Journal Title: Journal of Hypertension 24 Pages: 123-130
• [Presentation] Comparison of the protective effects of combination of various calcium channel blockers and an AT1 receptor blocker, olmesartan, on inflammatory vascular injury in mice (2008)
  • Author(s): Inaba S, Iwai M, Tomono Y, Kannno H, Senba I, Furuno M, Okayama H, Mogi M., Higaki J, Horiuchi M.
  • Organizer: 18th Scientific meeting International Society of Hypertension
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-06-19
• [Presentation] Delection of angiotensin IItype 2 receptor signaling increased vascular senescence with inhibition of methyl methanesulfonate sensitive2 (2008)
  • Author(s): Mogi M, J-M Min, Iwanami J, Sakata A, Fujita T, Tukuda K, Iwai M, Horiuchi M
  • Organizer: 18th Scientific meeting International Society of Hypertension
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-06-19
• [Presentation] Renin angiotensin system in cerebrospinal fluid of patients with neurodegenerative diseases (2008)
  • Author(s): Mogi M, Kawajiri M, Tsukuda K, Iwanami J, J-M Min, Sakata A, Fujita T, Iwai M, Miki T, Kira J-I, Horiuchi M
  • Organizer: 18th Scientific meeting International Society of Hypertension
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-06-19
• [Presentation] Enlargement of ischemic brain damage associated with oxidative stress after middle cerebral artery occlution in human renin/angiotensinogen transgenic mice (2008)
  • Author(s): Inaba S, Iwai M, Furuno M, Tomono Y,Kanno,H, Senba I, Okayama H , Mogi M, Higaki J, Horiuchi M
  • Organizer: 18th Scientific meeting International Society of Hypertension
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-06-19
• [Presentation] Lack of AT2 receptor attenuated adipocyte differentiation and increased adipocyte size in white adipose tissue of atherosclerotic mice treated with high cholesterol diet (2008)
  • Author(s): Iwai M, Tomono Y, Inaba S, Kanno H, Senba I, Furuno M, Mogi M, Horiuchi M
  • Organizer: 18th Scientific meeting International Society of Hypertension
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-06-19
• [Presentation] Lack of AT2 receptor attenuated adipocyte differentiation and increased adipocyte size in white adipose tissue of atherosclerotic mice treated with high cholesterol diet. (2008)
  • Author(s): Iwai M, et al.
  • Organizer: 22^<nd> Meeting of International Hypertension Society
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-06-18
• [Presentation] Sex defferent effect of AT2 recepor signaling on bra brain ischemic injury and cognitive function (2008)
  • Author(s): Sakata A, Mogi M, Iwanami J, Tsukuda K, Li J-M, Min L-J, Fujita T, Iwai M, Ito M, Horiuchi M
  • Organizer: 18th Scientific meeting International Society of Hypertension
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-06-14
• [Presentation] Roles of AT2 receptor in adipose tissue function and differentiation in atherosclerosis : Study with gene-deficient mice treated with high cholesterol diet (2007)
  • Author(s): Tomono Y, Iwai M, Inaba S, Kanno H, Mogi M, Horiuchi M
  • Organizer: 80th Scientific Sessions of American Heart Association
  • Place of Presentation: Olrando, Florida, USA
  • Year and Date: 2007-11-06
• [Presentation] Roles of AT2 Receptor in Adipose Tissue Fumction and Differentiation in Atherosclerosis :Study with Gene-deficient Mice Treated with High Cholesterol Diet (2007)
  • Author(s): Iwai M, et. al.
  • Organizer: Scientific Sessions 2007organiized by AHA
  • Place of Presentation: Orlando,Florida,USA
  • Year and Date: 2007-11-06
• [Presentation] Exaggeration of focal cerebral ischemia in transgenic mice carrying human renin and human angiotensinogen genes (2007)
  • Author(s): Inaba S, Iwai M, Tomono Y, Kanno H, Okayama H, Mogi M, Higaki J, Horiuchi M
  • Organizer: 61st Annual High Blood Pressure Research
  • Place of Presentation: Tucson AZ, USA
  • Year and Date: 2007-09-28
• [Presentation] Diabetes-associated cognitive impairment Is improved by a calcium channel blocker, nifedipine (2007)
  • Author(s): Tsukuda K, Mogi M, Li J-M, Iwanami J, Min L-J, Fujita T, Sakata A, Iwai M., Horiuchi M
  • Organizer: 61st Annual High Blood Pressure Research
  • Place of Presentation: Tucson AZ, USA
  • Year and Date: 2007-09-27
• [Presentation] Deletion of angiotensin II type 1 receptor enhances adipocyte model (2006)
  • Author(s): Iwai M, Tomono Y, Tomochika H, Chen R, Inaba S, Mogi M, Horiuchi M
  • Organizer: 79th Scientific Sessions of American Heart Association
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 2006-11-14
• [Presentation] Effectiveness of candesartan based combination therapy in essential hypertension. Ehime candesartan assessment trail (E-CAT) (2006)
  • Author(s): Okura T, Kurata M, Manabe S, Irita J, Enomoto D, Miyoshi K, Fukuoka T, Higaki J, Iwai M, Horiuchi M
  • Organizer: The 21st Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2006-10-18
• [Presentation] Effect of AT1 receptor blockade ameliorates adipose tissue inflammation and improves insulin resistance in type 2 diabetic KK-Ay mice (2006)
  • Author(s): Tomono Y, Iwai M, Chen R, Tomochika H, Mogi M, Horiuchi M
  • Organizer: The 21st Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2006-10-18
• [Presentation] Brain protective effect of bone marrow stromal cells is attenuated by inhibition of angiotensin II type 2 receptor signaling (2006)
  • Author(s): Iwanami J, Mogi M, Li J-M, Min L-J, Tuskuda K, Iwai M, Horiuchi M
  • Organizer: The 21st Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2006-10-18
• [Presentation] Knocking down of MMS2, a neuroprotective factor inhibits neural differentiation and impaired cognitive function after stroke (2006)
  • Author(s): Mogi M, Iwanami J, Li J-M, Min L-J, Tuskuda K, Iwai M, Horiuchi M
  • Organizer: The 21st Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2006-10-17
• [Presentation] Calcium channel blocker, nifedipine, inhibits MCP-1 expression in injured artery via inhibition of NF-Kb (2006)
  • Author(s): Gao X, Iwai M, Tomono Y, Chen R, Mogi M, Horiuchi M
  • Organizer: The 21st Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2006-10-17
• [Presentation] Effect of combination of pravastatin and olmesartan on glucose intolerance in type 2 diabetic KK-Ay mice (2006)
  • Author(s): Chen R, Iwai M, Tomono Y, Gao X, Mogi M, Horiuchi M
  • Organizer: The 21st Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2006-10-17
• [Presentation] Angiotensin II type 1 receptor blocker, candesartan ameliorates cognitive impairment in type-2 diabetes mice with improvement of insulin resistance (2006)
  • Author(s): Tuskuda K, Mogi M, Li J-M, Iwanami J, Min L-J, Chen R, Iwai M, Horiuchi M
  • Organizer: The 21st Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2006-10-17
• [Presentation] Synergistic induction of vascular smooth muscle cell senescence by aldosterone and angiotensin II (2006)
  • Author(s): Min L-J, Mogi M, Li J-M, Iwanami J, Tuskuda K, Iwai M, Horiuchi M
  • Organizer: The 21st Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2006-10-16
• [Presentation] Complex formation and nuclear translocation of SHR-1 and novel AT2 receptor-interacting protein enhances MMS2 upregulation, resulting in neural (2006)
  • Author(s): Li J-M, Mogi M, Iwanami J, Min L-J, Tuskuda K, Iwai M, Horiuchi M
  • Organizer: The 21st Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2006-10-16
• [Book] ARBによる酸化ストレス抑制作用.「The ARB ; Angiotensin II Receptor Blocker」(堀内正嗣編) (2006)
  • Author(s): 岩井將, 堀内正嗣
  • Publisher: メディカルレビュー社, 東京
• [Book] メディカルレビュー社, 東京 (2006)
  • Author(s): 岩井將, 堀内正嗣
  • Publisher: 脳・認知機能.「The ARB ; Angiotensin II Receptor Blocker」(堀内正嗣編)
• [Book] 性差医学におけるARB.「The ARB ; Angiotensin II Receptor Blocker」(堀内正嗣編) (2006)
  • Author(s): 岩井將, 堀内正嗣
  • Publisher: メディカルレビュー社, 東京