1999 Fiscal Year Annual Research Report

コレシストキニンA受容体遺伝子欠損と肥満、糖尿病の増悪および行動異常副題:自然発症CCK-A受容体遺伝子欠損動物および遺伝子ターゲッティング動物による検討

Research Project

Project/Area Number	09835022
Research Institution	Tokyo Metropolitan Institute of Gerontology
Principal Investigator	太田稔財団法人東京都老人総合研究所, 臨床生理部門, 研究助手 (70133634)
Co-Investigator(Kenkyū-buntansha)	宮坂京子財団法人東京都老人総合研究所, 臨床生理部門, 研究室長 (90166140)
Keywords	行動実験 / CCK / CCK受容体 / CCK-A受容体 / CCK-B受容体 / ノックアウトマウス / 肥満 / 糖尿病
Research Abstract	CCK-A受容体を遺伝子異常によって欠損している肥満(OLETF)ラットでは、種々の異常が認められた。脂肪吸収冗進は、食餌制限、運動負荷により体重増加を抑制することにより改善した。しかし、エネルギー代謝日内変動が平坦化することの原因は不明であり、体重増加抑制により、同様の好結果がのぞみうるのかどうかをしらべねばならないと思っている。放射状迷路実験は、餌の摂取を最終目標として、5分以内にどれだけ餌をとれるか、を検査しているものであるが、肥満ラットでは誤作動が多く、成績がよくない。しかし、この原因は、肥満とは直接の関係はないと解釈され、原因の確定はできていないが、CCK-A受容体欠損に基づいている可能性がつよい。このラットでは、特に運動能力には、異常をみとめていないので、線条体ドーパミン分泌に異常が認められなかったことは、意外ではないが、メタアンフェタミン中毒からの離脱時に差が見られたことは、今後さらに検討をくわえていく必要性を感じている。しかしながら、CCK-A受容体遺伝子ノックアウトマウスでは、通常飼育では、肥満(OLETF)ラットに認められたような著明な肥満はみられなかった。OLETFラットは、クローニングできたのはCCK-A受容体遺伝子のみであるが、兄弟交配をくり返すことにより確立された種であるので、複数の遺伝子異常が存在していると伝えられている。今後CCK-A受容体欠損マウスについて、食餌内容をはじめとする生活環境の変更や、他遺伝子異常をもつ種とのかけあわせなども計画していく必要があると思っている。

Research Products
(42 results)

All Other

All Publications (42 results)

[Publications] Miyasaka K.: "Role of cholecystokinin (CCK)-A-receptor in pancreatid growth in rats during suckling period : A study in a naturally occurring CCK-A-receptor gene 'knockout' rat"Pancreas. 14. 103-105 (1997)
[Publications] Kurosawa M.: "Interleukin-1 increases activity of the gastric vagal afferent nerve partly via stimulation of tye A CCK receptor in anesthetized rats"J. Auton Nerv Syst. 62. 72-78 (1997)
[Publications] Masuda M.: "Involvement of 5-hydroxytryptamine (5-HT) 3 receptor mechanisms in regulation of basal pancreatic secretion in conscious rats"J. Auton Nerv Syst. 62. 58-62 (1997)
[Publications] Miyasaka K.: "Aging impaired release of central and peripheral cholecystokinin (CCK) in old male, but not in female rats"J. Gerontol Med Sci. 52. M14-M18 (1997)
[Publications] Jimi A.: "Apoptosis in the pancreas of genetically diabetic rats with disrupted cholecystokinin (CCK-A) receptor gene"Pancreas. 14. 109-112 (1997)
[Publications] Masuda M.: "Central somatostatin prevents vagal efferent nerve excitation produced by TRH but not by 2-deoxy-D-grlucose"Am. J. Physiol.. 272. G351-G356 (1997)
[Publications] Ohta M.: "Changes in lymphocyte subpopulations in Otsuka Long Evans Tokushima Fatty Rats"Biomed Res. 18. 27-35 (1997)
[Publications] Miyasaka K.: "Regulation of cholecystokinin (CCK) release and transcription in a rat without gene expression of CCK-A receptor"Digestion. 58. 104-110 (1997)
[Publications] Miyasaka K.: "Retardation of pancreatic regeneration after partial pancreatectomy in a strain of rats without CCK-A receptor gene expression"Pancreas. 14. 391-399 (1997)
[Publications] Takata Y.: "Mouse cholecystokinin type-A receptor gene : Alternative splice acceptor site in exon 2"Gene. 187. 267-271 (1997)
[Publications] Miyasaka K.: "Cholinergic involvement in cholecystokinin (CCK) release by luminal oleic acid"J Auton Nerv Syst. 63. 179-182 (1997)
[Publications] Yamanouchi S.: "Decreased level of light-induced Fos expression in the suprachiasmatic nucleus of diabetic rats"Neurosci Lett. 227. 103-106 (1997)
[Publications] Miyasaka K.: "Stimulatory effect of synthetic luminal cholecystokinin releasing factor (LCRF) fragment (1-35) on pancreatic exocrine secretion in conscious rats"Pancreas. 15. 310-413 (1997)
[Publications] Takiguchi S.: "Disrupted cholecysotkinin type-A receptor (CCK-AR) gene in OLETF rats"Gene. 197. 169-175 (1997)
[Publications] Miyasaka K.: "Overexpression of cholecystokinin (CCK)-B/gastrin receptor gene in the stomach of naturally occuring CCK-A receptor gene knockout rats"Digestion. 59. 26-32 (1998)
[Publications] Masuda M.: "Inhibitory effect of central dopamine on basal pancreatic secretion"Am. J. Physiol.. 274. G29-G34 (1998)
[Publications] Miyasaka K.: "Role of cholecystokinin (CCK)-A receptor in pancreatic regeneration after pancreatic ductocclusion : A study in rats lacking CCK-A receptor gene expression"Pancreas. 16. 114-123 (1998)
[Publications] Takiguchi S.: "A disrupted cholecystokinin A receptor gene acted synergistically with ODB-1 gene to diabetic in obese rats"Am. J. Physiol.. 274. E265-E270 (1998)
[Publications] Kurosawa M.: "Response of the gastric vagal afferent activity to cholecystokinin in rats lacking type A cholecystokinin receptors"J Auton Nerv Syst. 75. 51-59 (1999)
[Publications] Nomoto S.: "Impaired learning and memory in OLETF rats without cholecystokinin (CCK)-A receptors"Physiol & Behav. 66. 869-872 (1999)
[Publications] Shimazoe T.: "Lowered entrainment function in the suprachiasmatic nucleus of Otsuka Long Evans Tokushima Fatty (OLETF) rats"J Pn. J. Pharmacol.. 80. 85-88 (1999)
[Publications] Funakoshi A.: "Lack of appropriate citation"J. Gastroenterol.. 34. 296 (1999)
[Publications] Miyasaka K.: "Disruption of cholecysotkinin (CCK)-B receptor gene did not modify bile or pancreatic secretion or pancreatic growth. A study in CCK-A receptor gene knockout mice"Pancreas. 19. 114-118 (1999)
[Publications] Tateishi K.: "Molecular cloning and expression of rat antisecretory factor and its intracellular localization"Biochem Cell Biol. 77. 223-228 (1999)
[Publications] Miyasaka K.: "Incidence of apoptosis in the pancreas of young and old rats"Arch. Gerontol. Geriatr.. 26. 235-245 (1998)
[Publications] Ichikawa M.: "Disappearance of dirunal rhythm of energy expenditure in genetically diabetic obese rats"Jpn J Physiol. 48. 211-214 (1998)
[Publications] Miyasaka K.: "Luminal feedback regulation,monitor peptide, CCK-releasing peptide,and CCK receptors"Pancreas. 16. 277-283 (1998)
[Publications] Miyasaka K.: "Central somatostatin diminished inhibitory action of central CGRP on pancreatic basal secretion in conscious rats"J Auton Nerv Syst. 73. 143-148 (1998)
[Publications] Funakoshi A.: "Mechanism of cholecystokinin-A receptor antagonist on human pancreatic exocrine secretion : Localization of CCK-A receptor in the human duodenum"Digestion. 60 (Supply). 75-80 (1999)
[Publications] Miyasaka K.: "Atropine-resistant secretion of a putative luminal cholecystokinin releasing peptide in conscious rats"Am J Physiol. 276. G287-G292 (1999)
[Publications] 小林悟: "高架式プラス迷路を用いたOLETFラットにおける不安類似行動。OLETFラットを用いた概日リズム機構の研究"OLETFラット研究会記録集. 4. 81-85 (1998)
[Publications] 宮坂京子: "インスリン非依存性糖尿病(NIDDM)を自然発症する肥満ラット(OLETF)における脂肪の腸管吸収の年齢変化"東京都老年学会誌. 5. 206-208 (1998)
[Publications] 宮坂京子: "コレシストキニン受容体"生体の科学特集受容体. 48. 403-406 (1997)
[Publications] 宮坂京子: "図解病態のメカニズム、膵外分泌調節"medicina. 35. 161-165 (1998)
[Publications] 宮坂京子: "CCK受容体"生体の科学特集受容体. 49. 381-383 (1998)
[Publications] 宮坂京子: "コレシストキニン(CCK)と膵機能"総合臨床. 48. 1649-1656 (1999)
[Publications] Miyasaka K.: "Role of CCK-A receptor in the regulation of pancreatic bicarbonate secretion in conscious rats : A study in naturally occurring CCK-A receptor gene knockout rats"Pancreas. 19. 217-223 (1999)
[Publications] Matsusue K.: "Expression of cholecystokinin type A receptor gene correlates with DNA demethylation during postnatal development of rat pancreas"Biochem Biophys Res Comm. 264. 29-32 (1999)
[Publications] Kawanami T.: "Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A receptor deficicent rats"Jpn J Pharmacol. 81. 339-345 (1999)
[Publications] 船越顕博: "インスリン依存性糖尿病(NIDDM)発症モデルOLETFラットに対するα-glucosidase inhibitor(voglibose)長期投与の膵及び小腸酵素活性に及ぼす効果"臨床と研究. 74. 2940-2944 (1997)
[Publications] 市川みね子: "OLETFラットにおける糖尿病発生とエネルギー代謝の日内リズム消失"OLETFラット研究会記録集. 4. 71-74 (1998)
[Publications] 島添隆雄: "OLETFラットを用いた概日リズム機構の研究"OLETFラット研究会記録集. 4. 75-80 (1998)

1999 Fiscal Year Annual Research Report

コレシストキニンA受容体遺伝子欠損と肥満、糖尿病の増悪および行動異常 副題:自然発症CCK-A受容体遺伝子欠損動物および遺伝子ターゲッティング動物による検討

Principal Investigator

太田 稔 財団法人 東京都老人総合研究所, 臨床生理部門, 研究助手 (70133634)

Research Products

[Publications] Miyasaka K.: "Role of cholecystokinin (CCK)-A-receptor in pancreatid growth in rats during suckling period : A study in a naturally occurring CCK-A-receptor gene 'knockout' rat"Pancreas. 14. 103-105 (1997)

[Publications] Kurosawa M.: "Interleukin-1 increases activity of the gastric vagal afferent nerve partly via stimulation of tye A CCK receptor in anesthetized rats"J. Auton Nerv Syst. 62. 72-78 (1997)

[Publications] Masuda M.: "Involvement of 5-hydroxytryptamine (5-HT) 3 receptor mechanisms in regulation of basal pancreatic secretion in conscious rats"J. Auton Nerv Syst. 62. 58-62 (1997)

[Publications] Miyasaka K.: "Aging impaired release of central and peripheral cholecystokinin (CCK) in old male, but not in female rats"J. Gerontol Med Sci. 52. M14-M18 (1997)

[Publications] Jimi A.: "Apoptosis in the pancreas of genetically diabetic rats with disrupted cholecystokinin (CCK-A) receptor gene"Pancreas. 14. 109-112 (1997)

[Publications] Masuda M.: "Central somatostatin prevents vagal efferent nerve excitation produced by TRH but not by 2-deoxy-D-grlucose"Am. J. Physiol.. 272. G351-G356 (1997)

[Publications] Ohta M.: "Changes in lymphocyte subpopulations in Otsuka Long Evans Tokushima Fatty Rats"Biomed Res. 18. 27-35 (1997)

[Publications] Miyasaka K.: "Regulation of cholecystokinin (CCK) release and transcription in a rat without gene expression of CCK-A receptor"Digestion. 58. 104-110 (1997)

[Publications] Miyasaka K.: "Retardation of pancreatic regeneration after partial pancreatectomy in a strain of rats without CCK-A receptor gene expression"Pancreas. 14. 391-399 (1997)

[Publications] Takata Y.: "Mouse cholecystokinin type-A receptor gene : Alternative splice acceptor site in exon 2"Gene. 187. 267-271 (1997)

[Publications] Miyasaka K.: "Cholinergic involvement in cholecystokinin (CCK) release by luminal oleic acid"J Auton Nerv Syst. 63. 179-182 (1997)

[Publications] Yamanouchi S.: "Decreased level of light-induced Fos expression in the suprachiasmatic nucleus of diabetic rats"Neurosci Lett. 227. 103-106 (1997)

[Publications] Miyasaka K.: "Stimulatory effect of synthetic luminal cholecystokinin releasing factor (LCRF) fragment (1-35) on pancreatic exocrine secretion in conscious rats"Pancreas. 15. 310-413 (1997)

[Publications] Takiguchi S.: "Disrupted cholecysotkinin type-A receptor (CCK-AR) gene in OLETF rats"Gene. 197. 169-175 (1997)

[Publications] Miyasaka K.: "Overexpression of cholecystokinin (CCK)-B/gastrin receptor gene in the stomach of naturally occuring CCK-A receptor gene knockout rats"Digestion. 59. 26-32 (1998)

[Publications] Masuda M.: "Inhibitory effect of central dopamine on basal pancreatic secretion"Am. J. Physiol.. 274. G29-G34 (1998)

[Publications] Miyasaka K.: "Role of cholecystokinin (CCK)-A receptor in pancreatic regeneration after pancreatic ductocclusion : A study in rats lacking CCK-A receptor gene expression"Pancreas. 16. 114-123 (1998)

[Publications] Takiguchi S.: "A disrupted cholecystokinin A receptor gene acted synergistically with ODB-1 gene to diabetic in obese rats"Am. J. Physiol.. 274. E265-E270 (1998)

[Publications] Kurosawa M.: "Response of the gastric vagal afferent activity to cholecystokinin in rats lacking type A cholecystokinin receptors"J Auton Nerv Syst. 75. 51-59 (1999)

[Publications] Nomoto S.: "Impaired learning and memory in OLETF rats without cholecystokinin (CCK)-A receptors"Physiol & Behav. 66. 869-872 (1999)

[Publications] Shimazoe T.: "Lowered entrainment function in the suprachiasmatic nucleus of Otsuka Long Evans Tokushima Fatty (OLETF) rats"J Pn. J. Pharmacol.. 80. 85-88 (1999)

[Publications] Funakoshi A.: "Lack of appropriate citation"J. Gastroenterol.. 34. 296 (1999)

[Publications] Miyasaka K.: "Disruption of cholecysotkinin (CCK)-B receptor gene did not modify bile or pancreatic secretion or pancreatic growth. A study in CCK-A receptor gene knockout mice"Pancreas. 19. 114-118 (1999)

[Publications] Tateishi K.: "Molecular cloning and expression of rat antisecretory factor and its intracellular localization"Biochem Cell Biol. 77. 223-228 (1999)

[Publications] Miyasaka K.: "Incidence of apoptosis in the pancreas of young and old rats"Arch. Gerontol. Geriatr.. 26. 235-245 (1998)

[Publications] Ichikawa M.: "Disappearance of dirunal rhythm of energy expenditure in genetically diabetic obese rats"Jpn J Physiol. 48. 211-214 (1998)

[Publications] Miyasaka K.: "Luminal feedback regulation,monitor peptide, CCK-releasing peptide,and CCK receptors"Pancreas. 16. 277-283 (1998)

[Publications] Miyasaka K.: "Central somatostatin diminished inhibitory action of central CGRP on pancreatic basal secretion in conscious rats"J Auton Nerv Syst. 73. 143-148 (1998)

[Publications] Funakoshi A.: "Mechanism of cholecystokinin-A receptor antagonist on human pancreatic exocrine secretion : Localization of CCK-A receptor in the human duodenum"Digestion. 60 (Supply). 75-80 (1999)

[Publications] Miyasaka K.: "Atropine-resistant secretion of a putative luminal cholecystokinin releasing peptide in conscious rats"Am J Physiol. 276. G287-G292 (1999)

[Publications] 小林悟: "高架式プラス迷路を用いたOLETFラットにおける不安類似行動。OLETFラットを用いた概日リズム機構の研究"OLETFラット研究会記録集. 4. 81-85 (1998)

[Publications] 宮坂京子: "インスリン非依存性糖尿病(NIDDM)を自然発症する肥満ラット(OLETF)における脂肪の腸管吸収の年齢変化"東京都老年学会誌. 5. 206-208 (1998)

[Publications] 宮坂京子: "コレシストキニン受容体"生体の科学 特集受容体. 48. 403-406 (1997)

[Publications] 宮坂京子: "図解病態のメカニズム、膵外分泌調節"medicina. 35. 161-165 (1998)

[Publications] 宮坂京子: "CCK受容体"生体の科学 特集受容体. 49. 381-383 (1998)

[Publications] 宮坂京子: "コレシストキニン(CCK)と膵機能"総合臨床. 48. 1649-1656 (1999)

[Publications] Miyasaka K.: "Role of CCK-A receptor in the regulation of pancreatic bicarbonate secretion in conscious rats : A study in naturally occurring CCK-A receptor gene knockout rats"Pancreas. 19. 217-223 (1999)

[Publications] Matsusue K.: "Expression of cholecystokinin type A receptor gene correlates with DNA demethylation during postnatal development of rat pancreas"Biochem Biophys Res Comm. 264. 29-32 (1999)

[Publications] Kawanami T.: "Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A receptor deficicent rats"Jpn J Pharmacol. 81. 339-345 (1999)

[Publications] 船越顕博: "インスリン依存性糖尿病(NIDDM)発症モデルOLETFラットに対するα-glucosidase inhibitor(voglibose)長期投与の膵及び小腸酵素活性に及ぼす効果"臨床と研究. 74. 2940-2944 (1997)

[Publications] 市川みね子: "OLETFラットにおける糖尿病発生とエネルギー代謝の日内リズム消失"OLETFラット研究会記録集. 4. 71-74 (1998)

[Publications] 島添隆雄: "OLETFラットを用いた概日リズム機構の研究"OLETFラット研究会記録集. 4. 75-80 (1998)

コレシストキニンA受容体遺伝子欠損と肥満、糖尿病の増悪および行動異常副題:自然発症CCK-A受容体遺伝子欠損動物および遺伝子ターゲッティング動物による検討

太田稔財団法人東京都老人総合研究所, 臨床生理部門, 研究助手 (70133634)

[Publications] 宮坂京子: "コレシストキニン受容体"生体の科学特集受容体. 48. 403-406 (1997)

[Publications] 宮坂京子: "CCK受容体"生体の科学特集受容体. 49. 381-383 (1998)