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コレシストキニンA受容体遺伝子多型と中年期発生肥満との関わりおよび分子機構の解明

Research Project

Project/Area Number 12877090
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionTokyo Metropolitan Institute of Gerontology

Principal Investigator

宮坂 京子  東京都老人総合研究所, 臨床生理部門, 研究室長 (90166140)

Co-Investigator(Kenkyū-buntansha) 増田 正雄  東京都老人総合研究所, 臨床生理部門, 研究助手 (20260284)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsコレシストキニン受容体 / 中年期肥満 / コレシストキニン / 分子機構 / 遺伝子多型
Research Abstract

肥満と胆石を併存する14例中9例にコレシストキニン(CCK)-A受容体遺伝子のプロモーター領域に2箇所の塩基置換(-128のGがT,-81のAがG)があることがわかった。健康診断(40歳以上)の2000例で40%に多型(type2-10を含む)があり、野生型は60%であった。
両方の置換が2本の染色体に生じたtype10は全体の2%であったが、これらは、血中レプチン、インスリン、体脂肪が有意に高く、CCK-A受容体遺伝子多型は、肥満に関わるsingle nucreotide polymorphism(SNP)の一つであると結論された。
ヒト胆嚢サンプル34例について、サザン法、還元法でメチル化状態を検討した。Northern blotをおこなったところ11例に遺伝子発現がみられた。そのうち1例のみが高度にメチル化されていたが、10例は軽度であった。一方、遺伝子発現が低下してNorthern blotで検出されなかった23例は、11例が低メチル化を呈していた。統計学的には、有意にメチル化が低いと遺伝子発現が増強していたが、多型との因果関係は、例数がたりず、明確でない。

Report

(2 results)
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Kurosawa M, Miyasaka K, et al.: "Cholecystokinin-8 (CCK-8) has no effect on heart rate in rats lacking CCK-A receptors"Peptides. 22. 1279-1284 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyasaka K, et al.: "Inhibitory effect of somatostatin on CCK release is independent of luminal LCRF content in conscious rats."Pancreas. 23. 414-420 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki S, Miyasaka K, et al.: "Importance of CCK-A receptor for gallbladder contraction and pancreatic secretion : A study in CCK-A receptor knockout mice."Jpn J Physiol. 51. 585-590 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hayashi H, Sato Y, Miyasaka K: "Increased lymphatic lipid transport in genetically diabetic obese rats"Am J Physiol. 282. G69-G76 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] MiyasakaK et al.: "Inhibitory effects of octreotide on luminal CCK releasing factor, plasma CCK, and pancreatic secretion in conscious rats."Pancreas. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takiguchi S, Sato Y, Miyasaka K, et al.: "Role of CCK-A receptor for pancreatic function in mice: A study in CCK-A receptor knockout mice."Pancreas. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshida Y, Miyasaka K.: "A PPAR agonist influenced daily profile of energy expenditure in genetically obese diabetic rats."Jpn J Pharm. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyasaka K, et al.: "Amylase secretion from dispersed human pancreatic acini : Neither CCK-A nor CCK-B receptors mediate amylase secretion in vitro"Pancreas. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyasaka K, et al.: "Increased energy metabolism and energy turnover in mice lacking cholecystokinin-B receptor."J Nutr. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takata Y, Miyasaka K, et al.: "Promoter analysis of human cholecystokinin (CCK) type-A receptor gene"J Gastro-enterol. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyasaka K, et al.: "Central orexin-A stimulates pancreatic exocrine secretion via vagus."Pancreas. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 木谷健一, 宮坂京子: "21世紀の高齢者疾患ほどう変わるか-病型、診断法、治療法など、8)肝。胆。膵疾患。"Geriatric Medicine (老年医学). 39. 70-75 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 船越顕博, 宮坂京子: "肥満と胆嚢機能、胆石"肝胆膵. 42. 41-49 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 増田正雄, 宮坂京子, 他: "Luminal cholecystokinin-releasing factor (LCRF)の分泌機能研究。"消化管ホルモン XIX. 38-40 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 宮坂京子, 太田稔, 船越顕博: "PPARγアゴニスト、ピオグリタゾンの脂肪吸収、エネルギー代謝におよぼす影響"消化と吸収. 24. 44-48 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 船越顕博: "CCK-A受容体遺伝子異常と生活習慣病。"日本消化器病学会雑誌. 97. 311-318 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 船越顕博: "コレシストキニン(CCK)受容体"臨床消化器内科. 15. 427-435 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 船越顕博: "膵外分泌とCCK受容体"胆と膵. 21. 205-212 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 宮坂京子: "膵外分泌の体液性調節-膵外分泌抑制ホルモン"胆と膵. 21. 193-198 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 木谷健一: "21世紀の高齢者疾患はどう変わるか-病型、診断法、治療法など、8)肝。胆。膵疾患"Geriatric Medicine(老年医学). 39. 70-75 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyasaka K: "Inhibitory effect of somatostatin on CCK release is independent of luminal LCRF content in conscious rats."Pancreas. (In press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Shimokata H: "Distribution of geriatric disease-related genotypes in the National Institute of Longevity Sciences, Longitudinal Study of Anging (NILS-LSA)."J Epidemiology. 10. S46-S55 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Funakoshi A: "Body fat content is related to cholecystokinin A receptor gene promotor polymorphism"FEBS Lett. 466. 264-266 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ichikawa M: "Difference in diurnal rhythm of energy expenditure between rats with obesity and glucose intolerance, and streptozotocin-induced diabetic rats."J Nutr. 130. 2562-2567 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohta M: "Mechanism of delayed gastric emptying in naturally occurring CCK-A receptor gene Knockout (OLETF) rats."Jpn J Physiol,. 50. 443-448 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shimazoe T: "Entrainment function in the suprachiasmatic nucleus of streptozotocin-induced diabetic rats."Jpn.J.Pharmacol.. 83. 355-358 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurosawa M: "Effects of systemic injection of interleukin-1β on gastric vagal afferent activity in rats lacking type A cholecystokinin receptors."Neurosci Lett. 293. 9-12 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 宮坂京子: "Advances in Aging and Health Research 1999"長寿科学振興財団. 140 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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