Effects of insulin on glucagon-stimulated glucose production in the conscious dog.
Effects of insulin on glucagon-stimulated glucose production in the conscious dog.
复制标题
胰岛素对清醒狗胰高血糖素刺激的葡萄糖产生的影响。
DOI：
10.1016/0026-0495(90)90192-f
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发表时间：
1990
期刊：
影响因子：
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通讯作者：
A. Cherrington
中科院分区：
文献类型：
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作者：
K. Steiner;P. Williams;W. Lacy;A. Cherrington
在禁食18小时的清醒狗中，评估了胰岛素和胰升糖素作为体内葡萄糖代谢主要调节剂的相对重要性。用[3-~3H]葡萄糖测定葡萄糖周转，用示踪剂([14C]丙氨酸)和A-V差值法测定在40分钟的控制期和3小时的激素期内的糖异生。在给予生长抑素和基础门脉内胰岛素和胰升糖素替代量的整个研究期间，血糖浓度(109±5 mg/dL)、葡萄糖生成量(3.24±0.30 mg/kg/min)和葡萄糖利用率(3.17±0.32 mg/kg/min)保持不变。控制期结束时，当高血糖素输注速度增加4倍时，血糖水平在1h内由107±4升至225±23 mg/dL，并持续升高。15min时葡萄糖产量由3.14±0.29增至7.66±0.51 mg/kg/min，3h后降至4.23±0.35 mg/kg/min。葡萄糖利用率从3.20±0.26上升到5.46±0.27 mg/kg/min。对照期末胰岛素输注速率增加4倍时，1h后葡萄糖产量由2.83±0.20降至1.16±0.57 mg/kg/min，之后略有升高(1.62±0.81 mg/kg/min)。葡萄糖利用率从2.92±0.30增加到8.12±1.12 mg/kg/min。通过输注葡萄糖维持正常血糖。胰岛素和胰升糖素输注速度增加四倍，导致葡萄糖产生在1小时内从3.03±0.23降至0.76±0.39 mg/kg/min，并在3小时内保持类似的抑制状态。葡萄糖利用率从2.95±0.20升至8.44±0.87 mg/kg/min，葡萄糖输注再次维持正常血糖。在胰岛素和胰升糖素维持在基础值的研究中，葡萄糖异生转化率增加(67±12%)，但丙氨酸的水平、分级提取和肝脏摄取没有显著变化。肝糖异生转化率(169%±42%)、肝匀浆丙氨酸萃取量(0.32±0.05~0.66±0.10)、丙氨酸摄取量(2.96±0.45~4.54±0.43)μ/kg/m in升高，丙氨酸水平下降(387±40~272±48μ/kg/m in)。胰岛素选择性升高与糖异生转化率增加(40%±25%)有关，与对照组相似，肝脏对丙氨酸的摄取和摄取无明显变化，丙氨酸水平略有下降(337±33至249±55μ/L)。伴随胰岛素和胰升糖素的增加，糖异生转化率保持不变(26%±21%)，但增加了肝脏对丙氨酸的提取分数(0.39±0.05至0.64±0.03)。肝脏丙氨酸摄取量无明显变化，但丙氨酸水平明显下降(35 3±40~174±16μ/L)。这些研究表明，在隔夜禁食清醒的狗中，胰岛素是一种有效的抑制胰高血糖素刺激肝糖原分解和糖异生的作用。然而，胰岛素不能通过抑制肝脏部分提取来限制丙氨酸摄取，相反，它通过限制肝外组织丙氨酸的净释放来阻止丙氨酸摄取的增加。
The relative importance of insulin and glucagon as primary regulators of glucose metabolism in vivo was assessed in 18-hour fasted conscious dogs. Glucose turnover was determined using [3-3H]glucose and gluconeogenesis was assessed using tracer ([14C]alanine) and A-V difference techniques during a 40-minute control period and a 3-hour period during which various hormonal perturbations were brought about. During the infusion of somatostatin and basal intraportal replacement amounts of insulin and glucagon for the entire study, the plasma glucose concentration (109 ± 5 mg/dL), glucose production (3.24 ± 0.30 mg/kg/min), and glucose utilization (3.17 ± 0.32 mg/kg/min) remained unchanged. When the glucagon infusion rate was increased fourfold at the end of the control period, the plasma glucose level increased from 107 ± 4 to 225 ± 23 mg/dL by 1 hour and remained elevated. Glucose production increased from 3.14 ± 0.29 to 7.66 ± 0.51 mg/kg/min by 15 minutes and decreased to 4.23 ± 0.35 mg/kg/min by 3 hours. Glucose utilization rose from a basal value of 3.20 ± 0.26 to 5.46 ± 0.27 mg/kg/min by 3 hours. When a fourfold increase in the insulin infusion rate was brought about at the end of the control period, glucose production decreased from 2.83 ± 0.20 to 1.16 ± 0.57 mg/kg/min by 1 hour, after which it increased slightly (1.62 ± 0.81 mg/kg/min). Glucose utilization increased from 2.92 ± 0.30 to 8.12 ± 1.12 mg/kg/min by 3 hours. Euglycemia was maintained by glucose infusion. Concomitant fourfold increases in the insulin and glucagon infusion rates caused glucose production to fall from 3.03 ± 0.23 to 0.76 ± 0.39 mg/kg/min by 1 hour and to remain similarly suppressed for 3 hours. Glucose utilization rose from 2.95 ± 0.20 to 8.44 ± 0.87 mg/kg/min and euglycemia was again maintained by glucose infusion. Gluconeogenic conversion increased (67 ± 12%) in the studies in which insulin and glucagon were kept at basal values, but the level, fractional extraction, and hepatic uptake of alanine did not change significantly. The selective increase in glucagon caused gluconeogenic conversion (169% ± 42%), hepatic fractional alanine extraction (0.32 ± 0.05 to 0.66 ± 0.10), and hepatic alanine uptake (2.96 ± 0.45 to 4.54 ± 0.43 μmol/kg/min) to increase, while the alanine level decreased (387 ± 40 to 272 ± 48 μmol/L). The selective increase in insulin was associated with an increase in gluconeogenic conversion (40% ± 25%) similar to that apparent in the control group, no change in the fractional extraction or uptake of alanine by the liver, and a small fall in alanine level (337 ± 33 to 249 ± 55 μmol/L). Concomitant increases in both insulin and glucagon left gluconeogenic conversion unchanged (26% ± 21%), but increased the fractional extraction of alanine by the liver (0.39 ± 0.05 to 0.64 ± 0.03). Hepatic alanine uptake did not change, but a decrease in the alanine level (353 ± 40 to 174 ± 16 μmol/L) was observed. These studies indicate that in the overnight fasted conscious dog, insulin is a potent inhibitor of the stimulatory effects of glucagon on hepatic glycogenolysis and gluconeogenesis. However, insulin is unable to limit alanine uptake by suppression of hepatic fractional extraction, instead it prevents increased alanine uptake by limiting the net release of alanine from extrahepatic tissues.