Clark P W, Jenkins A B, Kraegen E W
Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney New South Wales, Australia.
Am J Physiol. 1990 Apr;258(4 Pt 1):E701-7. doi: 10.1152/ajpendo.1990.258.4.E701.
Recent reports conflict on the effect that pentobarbital anesthesia has on basal glucose turnover in the rat. It is also unclear whether pentobarbital alters insulin suppressibility of hepatic glucose production (Ra). We examined these issues by performing basal and hyperinsulinemic euglycemic clamp studies in anesthetized and conscious animals. Ra and glucose utilization (Rd) were estimated using a steady-state infusion of 3-[3H]glucose. Pentobarbital anesthesia in normothermic rats transiently elevated plasma glucose but resulted in a sustained suppression of basal Ra (10.4 +/- 0.3 vs. conscious 13.2 +/- 0.9 mg.kg-1.min-1, P less than 0.05). In the insulin-stimulated state (110 mU/l), despite similar plasma glucose and insulin levels, clamp glucose infusion rate was significantly reduced in anesthetized animals (11.1 +/- 0.9 vs. conscious 23.6 +/- 1.3 mg.kg-1.min-1, P less than 0.001). This can be attributed to both a significantly lower insulin-stimulated Rd (15.4 +/- 1.3 vs. conscious 22.8 +/- 1.4 mg.kg-1.min-1, P less than 0.005) and reduced insulin suppression of Ra (4.3 +/- 0.8 vs. conscious -0.8 +/- 0.5 mg.kg-1.min-1, P less than 0.001; i.e., anesthetized 59% vs. conscious 100% reduction of basal Ra). Thus pentobarbital anesthesia significantly reduces basal Ra and induces hepatic insulin resistance (reduces Ra suppressibility). Pentobarbital effects are not dependent on induced hypothermia, but this exacerbates the metabolic perturbation. Caution should be used in extrapolating from the anesthetized to the conscious state.
近期报告在戊巴比妥麻醉对大鼠基础葡萄糖周转率的影响方面存在冲突。戊巴比妥是否会改变肝脏葡萄糖生成（Ra）的胰岛素抑制作用也尚不清楚。我们通过对麻醉和清醒动物进行基础及高胰岛素正常血糖钳夹研究来探讨这些问题。使用3-[3H]葡萄糖的稳态输注来估计Ra和葡萄糖利用率（Rd）。正常体温大鼠的戊巴比妥麻醉会使血浆葡萄糖短暂升高，但会导致基础Ra持续受到抑制（10.4±0.3对清醒状态下的13.2±0.9毫克·千克-1·分钟-1，P<0.05）。在胰岛素刺激状态（110 mU/l）下，尽管血浆葡萄糖和胰岛素水平相似，但麻醉动物的钳夹葡萄糖输注速率显著降低（11.1±0.9对清醒状态下的23.6±1.3毫克·千克-1·分钟-1，P<0.001）。这可归因于胰岛素刺激的Rd显著降低（15.4±1.3对清醒状态下的22.8±1.4毫克·千克-1·分钟-1，P<0.005）以及对Ra的胰岛素抑制作用减弱（4.3±0.8对清醒状态下的-0.8±0.5毫克·千克-1·分钟-1，P<0.001；即麻醉状态下基础Ra降低59%，清醒状态下降低100%）。因此，戊巴比妥麻醉会显著降低基础Ra并诱导肝脏胰岛素抵抗（降低Ra抑制性）。戊巴比妥的作用不依赖于诱导的体温过低，但这会加剧代谢紊乱。从麻醉状态推断到清醒状态时应谨慎。
