糖とインスリンによる腎血流生理調節と高血圧発症
機序
著者
森 建文
様式C-18
<はしがき>
近年､食事の欧米化と運動不足により肥満が増加し､糖尿病やメタポリツクシンドロームの患者
が増えている｡これらの疾患ではしばしば高血圧を合併し､腎障害や血管障害の独立したリスク
ファクターになっている｡しかしながら､糖尿病やメタポリツクシンドロームにおける高血圧の発症
機序には未だ不明な点が多い｡
本研究では糖とインスリンに着日し､腎血流調節作用と高血圧発症機序を明らかにした｡その結
果､血糖の上昇はインスリンに依存せず腎尿細管でのブドウ糖の再吸収と散化ストレスを介して
腎髄賞血流を漉らし､高血圧発症に関与することが明らかとなった｡本研究により糖尿病やメタ
ポリツクシンドロームで高血圧発症機序の-つが明らかとなり､今後の治療戦略の開発につなが
ると考えられる｡
本研究の施行にあたり､多大な協力をいただいた関係各位に感謝します｡
平成19年5月
研究組織
研究代表者:森建文(東北大学高等教育開発推進センター助手)
研究分担者:伊藤貞轟 く東北大学医学部教授)
交付決定額(配分額) (金額単位:円)
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間接経費 俘xﾇb
平成17年度 ﾃ# ﾃ 0 ﾃ# ﾃ 平成18年度 ﾃC ﾃ 0 ﾃC 稔計 緜 ﾃ 0 ﾃc ﾃ研究発表
(1)学会誌等(発表者名､テーマ名､学会誌名､巻号､年月日)
I. Albert Sarkis, Osamu lto, Takefumi Mori, MasahiroKohzuki, Sadayoshi lto, JosephVerbalis,
Allen W. Cowley, Jr. and Richard ∫. Roman. Cytochrome P-450-dependent metabolism of
arachidonic acid in the kidney of rats with diabetes insipidus. Am I J%ysJ'oJ.
2005;289 (6) :F1333-40.
2. Takefumi Mori. Padden Glocka, Mingyu Liang, Meredith Skelton, Mary Kaldunski, Allen W. cowley, Jr. Specific role of renal per fusion pressure in the development of renal injury
in I)ahl salt-sensitive rats HyperlensJ'on. 2006: 46: 821
3. Takefumi Mori, Allen W. Cowley, Jr. and Sadayoshi lto.
Molecular Mechanisms and Therapeutic Strategies of Chronic Renal Injury: physiological Role of Angiotensin IIIInduced Oxidative Stress in Renal
Medulla. Jj加rmdCOJ ▲fcl'. 2006;loo(1) :2-8. (Review)
4. SusuTnu Ogawa, Takefumi Mori. Kazuhiro Nako, Taro Kato, Kazuhisa Takeuchi and Sadayoshi lto. Angiotensin II type-1 receptors blockers reduce urinary oxidative stress markers
in hypertensive diabetic nephropathy. HyperlensJ'on. 2006:47 (4) :699-705.
5. Susutnu Ogawa, Kazuhisa Takeuchi, Takefumi Mori, Kazuhiro Nako and Sadayoshi lto. Spironolactone further reduces urinary albumin excretion and plasma B-type natriuretic peptide levels in hypertensive type II diabetes treated with angiotensin-converting
enzyme inhibitor. CJJ'n Exp j惣armacoJ J惣yTJ'01. 2006;33 (516) :477-9.
6. Takefumi Mori, Yoshimi Yoneki, Satoshi Endo, Susumu Ogawa, Chun-hua Jin, Kazuhiro Nako, Sadayoshi lto. Hypergricemia induced hypertensive action in insulin resistant Dahl salt
sensitive rats.伽ertensJ'on. 2006;48:e77
7. Chun-hua Jim, Takefumi Mori, Susunu Ogawa, Satoshi Endo, Yoshimi Yoneki, Kazuhiro Nako, Sad-ayoshi lto. Glucose reduces renal nedullary circulation by induction of oxidative
stress in renal medulla. Hypertensjon. 2006; 48:e30
8. Susumu Ogawa, Kazuhisa Takeuchi, Takefumi Mori, Kazuhiro Nako, Yoshitaka Tsubono,
･ Sadayoshi lto. Effects of Monotherapy of Temocapril or Candesartan with Dose Increments
or Combination Therapy with Both Drugs on the Suppression of Diabetic Nephropathy.
Hyperlensl'on Res. 2007:30:325-334.
9. Takefumi Mori, Paul O'connor, Allen W. Cowley, Jr. Enhanced superoxide production in
renal outer medulla of Dahl sal卜sensitive rats reduces NO tubular-vascular cross-talk.
伽erlensl'on. 2007 in Press.
10.森 建文､伊藤貞嘉
心腎連関: Cardiorenal Risk,心疾患における腎機能調節の異常とその機序､ 血管医学Vol. 6/No. 6､ 57ト576､ 2005 ll.森 建文､伊藤貞嘉､ Allen W. Cowley,Jr.アンジオテンシン日による腎髄質血流調節機序と高血圧性腎障害への影響
腎と透析Vol. 60/No. 2､ 30ト306､ 200612.森 建文､伊藤貞義
慢性腎臓病(CKD)と心血管リスク､ CKDの病態:心臓と腎臓の機能的関連
血圧Vol. 13/No.4､ 30-34､ 200613.森 建文､伊藤貞嘉
腎髄質循環
臨床高血圧Vol. 12/No. 3､ 16-29､ 2006ll.口頭発表(発表者名､テーマ名､学会等名､年月日)
1. Takefumi Mori, Chun-Hua Jin, Sadayoshi Ito, Allen W. Cowley, Jr. Actions of renal medullary hydrogen
peroxide on intracellular Ca2+ levels in contractile vasa recta pericytes･ 4th Asian-Pacific Congress of Hypertension 6/3/2005, Soul, South Korea･ (Oral)
2. Susumu Ogawa, Takefumi Mori, Kazuhiro Nako, Taro Kato, Kazuhisa Takeuchi, Sadayoshi Ito･
markers in patients with diabetic nephropathy1 4thAsian-Pacific Congress of Hypertension 6/4/2005,
Soul, South Korea. (Oral)
3. Chun-Hua Jin, Takefumi Mori, Masayuki Kanazawa, Tetsuya Ootaka, Hiroshi Sato, Masahiro Kozuki,
Sadayoshi lto･ Inhibition of adenosine Al receptor reduce proteinuria by interaction with renin
angiotensin system in Dahl salt-sensitive rats･ 3rd World Congress of Nephrology 6/29/2005, Singapore,
Singapore. (Poster)
4. Takefumi Mori, Padden Glocka, Mingyu Liang, Meredith Skelton, Mary Kaldunski, Allen W･ Cowley, Jr･ SpeciflC role of renal perfusion pressure in the development of renal injury in Dahl salt-sensitive rats･
American HeartAsSociation High Blood Pressure Council 9/23/2005, Washington DC, USA･ (Peer
reviewed, Oral)
5. Satoshi Endo, Takefumi Mori, Yoshimi Yoneki, Goro Tokudome, Tatsuo Hosoya, Sadayoshi lto. High
salt intake attenuates antihypertenSive actions or angiotensin II receptor blockade with induction of renal
oxid-a-tive stress. Experimental Biology 4/3/2006, San Francisco, USA. (Poster)
6. Chum-hua Jin, TakefumiMori, Susumu Ogawa, Satoshi Endo, Yoshimi Yoneki, Kazuhiro Nako,
Sa血yoshi lto･ Glucose reduces renal medullary circulation by induction of oxi血tive stress in renal
medulla. American Heart Association High Blood Pressure Council 10/05/2006, Sam Anto山0, USA･
(Peer reviewed, Oral)
7. TakefumiMori, YoshimiYoneki, Satoshi Endo, Susumu Ogawa, Chun-hua Jin, Kazuhiro Nako,
Sadayoshi Ito. HypergrlCemia induced hypertensive action in insulin resistant Dahl salt sensitive rats･ American Heart Association High Blood Pressure Council 10/05/2006, Sam Antonio, USA･ (Peer
reviewed, Poster)
8. Satoshi Endo, TakefumiMori, Yoshimi Yoneki, Susumu Ogawa, Kazuhiro Nako, Goro Tokudome,
Tatsuo Hosoya, Sadayoshi ItoI Sucrose intake induces oxidative stress and ang10tenSin ll dependent
hypertension in insulin resistant Dahl salt-sensitive rats･ The 2 1 st Scientific Meeting of the international
Society or Hypertension. Fukuob, Japan･ 1 0/1 8/2006 (Poster)
9. YoshimiYoneki, TakefumiMori, Osamu Ito, Tsuneo Ishizuka, Satoshi Endo, Ken Omata, Masahiro
Kozuki, Sa血yoshi lto･ An血ogen induced P4504A cause hypertension in spontaneously hypertensive
rats. The 2lst Scientific Meeting of the lntemational Society of Hypertension. Fukuoka, Japan1
1 0/1 8/2006 (Poster)
10. Takefumi Mori, Chun-hua Jin, Susumu Ogawa, Yoshimi Yoneki, Md. Matlubur Ralman, Satoshi Endo,
Takashi Nakamichi, Kazuhiro Nako and Sadayoshi Ito. Reduction of renal medullary circulation with
acute glucose loading via sodium-glucose transporter and oxi血tive stress･ International Symposium or The Ki血ey and Hypertension, Sen血i, Japan, 1 0/2 I/2006 (Oral)
ll. YoshimiYoneki, TakefumiMori, Satoshi Endo, Susumu Ogawa, Md. MatluburRalman, Takashi
Nakamicbi, Kaz血iro Nako and Sadayoshi lto. Sucrose induced hypertensive action in insulin resistant
Dahl salt sensitive rats. International Symposium of The Kidney and Hypertension, Sendai, Japan,
1 0/2 1/2006 (Poster)
1 2. Takashi Nakamichi, TakefumiMori, YoshimiYoneki, Satoshi Endo, Matlubur Ralman, Takuma Hosoya,
Hiroshi Sato, Toshinobu Sato, Sadayoshi Ito. Enhanced oxidative stress on progression of chronic Thy- 1
1 3. Yoshimi Yoneki, Takefumi Mori, Susumu Ogawa, Satoshi Endo, Matlubur Ralman, Takashi Nakamichi,
Takuma Hosoya, Wanjun Zhu, Chunyan Hu, Kazuhiro Nako, Sadayoshi lto･ Pressure independent
