Glybuzoleの膵α細胞機能に及ぼす影響に関する実験的および臨床的研究 Experimental and Clinical Studies on the Effect of Glybuzole upon the Alpha Cell Function of the Pancreas

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Abstract

glybuzoleの膵グルカゴン分泌に対する効果をみるため, 6頭の麻酔犬を用い, 開腹下に上膵十二指腸動脈に91ybuzole 100mgを10分間に注入した. 膵静脈血中の血漿インスリンは3分で164.0±30.6より352.3±99.3μU/mlと上昇した. 血漿グルカゴンは1.34±0.12より6分後に0.92±0.18mμg/mlと低下し, 注入終了後は徐々に増加した. 6頭のうち3頭の犬では, 他のsulfonylurea剤との比較を行うため, その後40分間隔でtolbutamideとglibenclamideを注入したが, glybuzole 100mgはtolbutamide 200mg, glibenclamide lmgよりも膵グルカゴン分泌を強く抑制した.<BR>2) 5人の成人型糖尿病患者について, 約1ヵ月間のglybuzoleによる治療を行い, その前後にアルギニン負荷試験を行って, 膵グルカゴン反応の変動をみた. 塩糖値は治療前に比し, 治療後に空腹時を含め全時間で有意に低下した. この際の膵グルカゴン値は空腹時, 5分および20分値に, 治療後の有意の低下がみられた. これはsulfonamide剤の長期投与により, アミノ酸による膵グルカゴン分泌が抑制されることを示唆する.

To determine the direct effect of glybuzole upon the secretion of pancreatic glucagon, 100mg of glybuzole was infused for 10 minutes into the pancreatic artery of six anesthetized dogs.Blood glucose in the femoral artery decreased gradually 15 minutes and later following glybuzole infusion. Plasma insulin in the pancreatic vein rcse from a base line of 164.0±30.6 to a peak of 352.3±99.3μU/m/ at 3 minutes (p<.05). Plasma glucagon in the pancreatic vein de;reased promptly from a base line of 1.34±0.12 mpg/m/ and reached the nadir of 0.92±0.18 mpg/m/ at 6 minutes (p<.05). The glucagon level, however, returned gradually to the initial level after the withdrawal of the glybuzole infusion. To compare the effect of glybuzole with the other sulfonylurea drugs, glybuzole, tolbutamide and glibenclamide were infused successively for ten minutes into the pancreatic artery at 40-minute intervals in a group of three dogs. 100 mg of glybuzole induced a more marked decrease in the plasma level of glucagon compared with 200mg of tolbutamide or lmg of glibenclamide.<BR>Pancreatic glucagon response to arginine infusion was investigated before and after the treatment with glybuzole in 5 diabetic patients. Approximately one month after glybuzole administration, blood glucose levels, either fasting or after arginine infusion, were significantly lower than those before the treatment. Plasma glucagon levels during arginine infusion tests were lower after the glybuzole treatment compared with those before the treatment. Significant changes in the plasma glucagon were observed before and 5 and 20 minutes after the start of the arginine infusion.<BR>These results showed the direct effect as well as the chronic effect of glybuzole upon the alpha cell function of the pancreas.

Journal

  • Journal of the Japan Diabetes Society

    Journal of the Japan Diabetes Society 18(2), 149-155, 1975

    THE JAPAN DIABETES SOCIETY

Codes

  • NII Article ID (NAID)
    130004336484
  • NII NACSIS-CAT ID (NCID)
    AN00166576
  • Text Lang
    UNK
  • ISSN
    0021-437X
  • NDL Article ID
    1598737
  • NDL Source Classification
    SC311(代謝異常)
  • NDL Source Classification
    ZS21(科学技術--医学--内科学)
  • NDL Call No.
    Z19-401
  • Data Source
    NDL  J-STAGE 
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