Sindelar D K, Chu C A, Venson P, Donahue E P, Neal D W, Cherrington A D
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA.
Diabetes. 1998 Apr;47(4):523-9. doi: 10.2337/diabetes.47.4.523.
The ability of portal vein insulin to control hepatic glucose production (HGP) is debated. The aim of the present study was to determine, therefore, if the liver can respond to a selective decrease in portal vein insulin. Isotopic ([3H]glucose) and arteriovenous difference methods were used to measure HGP in conscious overnight fasted dogs. A pancreatic clamp (somatostatin plus basal portal insulin and glucagon) was used to control the endocrine pancreas. A 40-min control period was followed by a 180-min test period. During the latter, the portal vein insulin level was selectively decreased while the arterial insulin level was not changed. This was accomplished by stopping the portal insulin infusion and giving insulin peripherally at half the basal portal rate (PID, n=5). In a control group (n=5), the portal insulin infusion was not changed and glucose was infused to match the hyperglycemia that occurred in the PID group. A selective decrease of 120 pmol/l in portal vein insulin was achieved (basal, 150+/-36 to last 30 min, 30+/-12 pmol/l) in the absence of a change in the arterial insulin level (basal, 30+/-3 to last 30 min, 36+/-4 pmol/l). Neither arterial nor portal insulin levels changed in the control group (30+/-6 and 126+/-30 pmol/l, respectively). In response to the selective decrease in portal vein insulin, net hepatic glucose output (NHGO) increased significantly, from 8+/-1 (basal) to 30+/-6 and 14+/-2 micromol x kg(-1) x min(-1) by 15 min and the last 30 min (P < 0.05) of the experimental period, respectively. Arterial plasma glucose increased from 5.9+/-0.2 (basal) to 10.5+/-0.4 micromol/l (last 30 min). Three-carbon gluconeogenic precursor uptake fell from 11.2+/-2.9 (basal) to 5.9+/-0.7 micromol x kg(-1) x min(-1) (last 30 min), and thus a change in gluconeogenesis could not account for any of the increase in NHGO. With matched hyperglycemia (basal, 5.5+/-0.3 to last 30 min, 10.5+/-0.8 micromol/l) but no change in insulin, NHGO decreased from 12+/-1 (basal) to 0 (-1+/-6 micromol x kg(-1) x min(-1), last 30 min, P < 0.05) and hepatic gluconeogenic precursor uptake did not change (basal, 8.0+/-1.7 to last 30 min, 8.9+/-2.2 micromol x kg[-1] x min[-1]). Thus, the liver responds rapidly to a selective decrease in portal vein insulin by markedly increasing HGP as a result of increased glycogenolysis. These studies indicate that after an overnight fast, basal HGP (glycogenolysis) is highly sensitive to the hepatic sinusoidal insulin level.
门静脉胰岛素控制肝葡萄糖生成（HGP）的能力存在争议。因此，本研究的目的是确定肝脏是否能对门静脉胰岛素的选择性降低做出反应。采用同位素（[3H]葡萄糖）和动静脉差值法在清醒过夜禁食的犬中测量HGP。使用胰腺钳夹（生长抑素加基础门静脉胰岛素和胰高血糖素）来控制内分泌胰腺。先有40分钟的对照期，随后是180分钟的测试期。在测试期内，门静脉胰岛素水平选择性降低，而动脉胰岛素水平不变。这是通过停止门静脉胰岛素输注并以基础门静脉速率的一半外周给予胰岛素来实现的（门静脉胰岛素降低组，n = 5）。在对照组（n = 5）中，门静脉胰岛素输注不变，并输注葡萄糖以匹配门静脉胰岛素降低组出现的高血糖。在动脉胰岛素水平无变化的情况下（基础值，30±3至最后30分钟，36±4 pmol/l），门静脉胰岛素选择性降低了120 pmol/l（基础值，150±36至最后30分钟，30±12 pmol/l）。对照组的动脉和门静脉胰岛素水平均未改变（分别为30±6和126±30 pmol/l）。响应门静脉胰岛素的选择性降低，肝葡萄糖净输出（NHGO）显著增加，在实验期的15分钟时从8±1（基础值）增加到30±6，在最后30分钟时增加到14±2 μmol·kg-1·min-1（P < 0.05）。动脉血浆葡萄糖从5.9±0.2（基础值）增加到10.5±0.4 μmol/l（最后30分钟）。三碳糖异生前体摄取从1l.2±2.9（基础值）降至5.9±0.7 μmol·kg-1·min-1（最后30分钟），因此糖异生的变化不能解释NHGO增加的任何原因。在血糖匹配升高（基础值，5.5±0.3至最后30分钟，10.5±0.8 μmol/l）但胰岛素无变化的情况下，NHGO从12±1（基础值）降至0（-1±6 μmol·kg-1·min-1，最后30分钟，P < 0.05），肝糖异生前体摄取未改变（基础值，8.0±1.7至最后30分钟，8.9±2.2 μmol·kg-1·min-1）。因此，肝脏通过糖原分解增加导致HGP显著增加，从而对门静脉胰岛素的选择性降低做出快速反应。这些研究表明，过夜禁食后，基础HGP（糖原分解）对肝窦胰岛素水平高度敏感。
