Flattem N, Igawa K, Shiota M, Emshwiller M G, Neal D W, Cherrington A D
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Diabetes. 2001 Feb;50(2):367-75. doi: 10.2337/diabetes.50.2.367.
The responses of the pancreatic alpha- and beta-cells to small changes in glucose were examined in overnight-fasted conscious dogs. Each study consisted of an equilibration (-140 to -40 min), a control (-40 to 0 min), and a test period (0 to 180 min), during which BAY R3401 (10 mg/kg), a glycogen phosphorylase inhibitor, was administered orally, either alone to create mild hypoglycemia or with peripheral glucose infusion to maintain euglycemia or create mild hyperglycemia. Drug administration in the hypoglycemic group decreased net hepatic glucose output (NHGO) from 8.9 +/- 1.7 (basal) to 6.0 +/- 1.7 and 5.8 +/- 1.0 pmol x kg(-1) x min(-1) by 30 and 90 min. As a result, the arterial plasma glucose level decreased from 5.8 +/- 0.2 (basal) to 5.2 +/- 0.3 and 4.4 +/- 0.3 mmol/l by 30 and 90 min, respectively (P < 0.01). Arterial plasma insulin levels and the hepatic portal-arterial difference in plasma insulin decreased (P < 0.01) from 78 +/- 18 and 90 +/- 24 to 24 +/- 6 and 12 +/- 12 pmol/l over the first 30 min of the test period and decreased to 18 +/- 6 and 0 pmol/l by 90 min, respectively. The arterial glucagon levels and the hepatic portal-arterial difference in plasma glucagon increased from 43 +/- 5 and 4 +/- 2 to 51 +/- 5 and 10 +/- 5 ng/l by 30 min (P < 0.05) and to 79 +/- 16 and 31 +/- 15 ng/l by 90 min (P < 0.05), respectively. In euglycemic dogs, the arterial plasma glucose level remained at 5.9 +/- 0.1 mmol/l, and the NHGO decreased from 10 +/- 0.6 to -3.3 +/- 0.6 pmol x kg(-1) x min(-1) (180 min). The insulin and glucagon levels and the hepatic portal-arterial differences remained constant. In hyperglycemic dogs, the arterial plasma glucose level increased from 5.9 +/- 0.2 to 6.2 +/- 0.2 mmol/l by 30 min, and the NHGO decreased from 10 +/- 1.7 to 0 pmol x kg(-1) x min(-1) by 30 min. The arterial plasma insulin levels and the hepatic portal-arterial difference in plasma insulin increased from 60 +/- 18 and 78 +/- 24 to 126 +/- 30 and 192 +/- 42 pmol/l by 30 min, after which they averaged 138 +/- 24 and 282 +/- 30 pmol/l, respectively. The arterial plasma glucagon levels and the hepatic portal-arterial difference in plasma glucagon decreased slightly from 41 +/- 7 and 4 +/- 3 to 34 +/- 7 and 3 +/- 2 ng/l during the test period. These data show that the alpha- and beta-cells of the pancreas respond as a coupled unit to very small decreases in the plasma glucose level.
在过夜禁食的清醒犬中研究了胰腺α细胞和β细胞对葡萄糖微小变化的反应。每项研究包括一个平衡期（-140至-40分钟）、一个对照期（-40至0分钟）和一个测试期（0至180分钟），在此期间，口服糖原磷酸化酶抑制剂BAY R3401（10mg/kg），单独使用以造成轻度低血糖，或与外周葡萄糖输注联合使用以维持血糖正常或造成轻度高血糖。低血糖组给药后30分钟和90分钟时，肝脏葡萄糖净输出量（NHGO）从8.9±1.7（基础值）分别降至6.0±1.7和5.8±1.0pmol·kg⁻¹·min⁻¹。结果，动脉血浆葡萄糖水平在30分钟和90分钟时分别从5.8±0.2（基础值）降至5.2±0.3和4.4±0.3mmol/L（P<0.01）。在测试期的前30分钟内，动脉血浆胰岛素水平以及肝门静脉-动脉血浆胰岛素差值（P<0.01）从78±18和90±24分别降至24±6和12±12pmol/L，到90分钟时分别降至18±6和0pmol/L。动脉胰高血糖素水平以及肝门静脉-动脉血浆胰高血糖素差值在30分钟时从43±5和4±2分别升至51±5和10±5ng/L（P<0.05），到90分钟时分别升至79±16和31±15ng/L（P<0.05）。在血糖正常的犬中，动脉血浆葡萄糖水平维持在5.9±0.1mmol/L，NHGO在180分钟时从10±0.6降至-3.3±0.6pmol·kg⁻¹·min⁻¹。胰岛素和胰高血糖素水平以及肝门静脉-动脉差值保持恒定。在高血糖犬中，动脉血浆葡萄糖水平在30分钟时从5.9±0.2升至6.2±0.2mmol/L，NHGO在30分钟时从10±1.7降至0pmol·kg⁻¹·min⁻¹。动脉血浆胰岛素水平以及肝门静脉-动脉血浆胰岛素差值在30分钟时从60±18和78±24分别升至126±30和192±42pmol/L，之后平均分别为138±24和282±30pmol/L。在测试期内，动脉血浆胰高血糖素水平以及肝门静脉-动脉血浆胰高血糖素差值从41±7和4±3略有降至34±7和3±2ng/L。这些数据表明，胰腺的α细胞和β细胞作为一个耦合单元对血浆葡萄糖水平的非常小的下降作出反应。
