Miller J D, Ganguli S, Sperling M A
Diabetes. 1983 May;32(5):439-44. doi: 10.2337/diab.32.5.439.
To investigate whether inhibition of prostaglandin synthesis affects hormone-induced glucose dynamics, we measured glucose turnover in response to glucagon alone (5 ng . kg-1 min-1) or combined with epinephrine (0.1 microgram . kg-1 min-1) in conscious trained dogs (N = 6) on three separate occasions in each animal: (1) during a control saline infusion, (2) during infusion of indomethacin, and (3) during infusion of sodium salicylate. Glucose production (Ra) and utilization (Rd) were determined by isotope dilution using the nonrecycling label 3-3H glucose. In controls, glucagon levels (IRG) rose from a basal of 44 +/- 12 to 260 +/- 40 pg/ml (mean +/- SEM) during glucagon infusion; basal epinephrine levels (EPI) of 150 +/- 20 pg/ml were unaffected by glucagon infusion but rose four- to fivefold during combined glucagon/epinephrine infusion. Plasma glucose rose transiently from 95 +/- 1 to a peak of 136 +/- 13 mg/dl after 20 min of glucagon; infusion of EPI resulted in a second glycemic response with a peak of 148 +/- 9 mg/dl. Ra increased transiently from 2.9 +/- 0.2 to a peak of 7.9 +/- 1.4 mg . kg-1 min-1 during glucagon alone with a second rise to 6.2 +/- 0.8 mg . kg-1 min-1 10 min after beginning EPI. With glucagon alone, Rd paralleled Ra but addition of EPI resulted in a relative fall in Rd. Insulin (IRI) rose from 9 +/- 1 microU/ml to 29 +/- 6 microU/ml with glucagon but IRI fell despite the second glycemic response during EPI. When either indomethacin or salicylate was infused, basal IRI, IRG, EPI, glucose, Ra and Rd were unaffected and were similar to controls. Although plasma levels of IRG and EPI during glucagon or glucagon plus epinephrine infusion were also similar to controls, the glycemic response was reduced (P less than 0.05). This attenuation of glycemic response was due to a reduction of stimulated Ra (P less than 0.05) and not to an increase in Rd. Changes in IRI paralleled the reduction in glycemic response. Thus, both indomethacin and salicylate blunt the glycemic response to glucagon and glucagon plus epinephrine by attenuating glucose production and not by enhancing glucose utilization or insulin secretion. These results with two prostaglandin synthesis inhibitors suggest that prostaglandins modulate the hepatic effects of glucagon and epinephrine.
为了研究前列腺素合成的抑制是否会影响激素诱导的葡萄糖动态变化，我们在清醒的经训练的犬（N = 6）身上，分三次单独测量了它们对单独的胰高血糖素（5 ng·kg⁻¹·min⁻¹）或与肾上腺素联合使用（0.1 μg·kg⁻¹·min⁻¹）的葡萄糖周转率：（1）在生理盐水对照输注期间，（2）在吲哚美辛输注期间，以及（3）在水杨酸钠输注期间。使用非循环标记的3-³H葡萄糖通过同位素稀释法测定葡萄糖生成（Ra）和利用（Rd）。在对照组中，胰高血糖素输注期间，胰高血糖素水平（IRG）从基础值44±12 pg/ml升至260±40 pg/ml（平均值±标准误）；基础肾上腺素水平（EPI）为150±20 pg/ml，不受胰高血糖素输注影响，但在胰高血糖素/肾上腺素联合输注期间升高了四至五倍。胰高血糖素输注20分钟后，血浆葡萄糖从95±1 mg/dl短暂升至峰值136±13 mg/dl；肾上腺素输注导致第二次血糖反应，峰值为148±9 mg/dl。单独使用胰高血糖素时，Ra从2.9±0.2 mg·kg⁻¹·min⁻¹短暂升至峰值7.9±1.4 mg·kg⁻¹·min⁻¹，在开始输注肾上腺素10分钟后第二次升至6.2±0.8 mg·kg⁻¹·min⁻¹。单独使用胰高血糖素时，Rd与Ra平行，但加入肾上腺素后导致Rd相对下降。胰岛素（IRI）在胰高血糖素作用下从9±1 μU/ml升至29±6 μU/ml，但尽管在肾上腺素作用期间出现了第二次血糖反应，IRI仍下降。当输注吲哚美辛或水杨酸盐时，基础IRI、IRG、EPI、葡萄糖、Ra和Rd均未受影响，且与对照组相似。尽管胰高血糖素或胰高血糖素加肾上腺素输注期间的IRG和EPI血浆水平也与对照组相似，但血糖反应降低（P＜0.05）。这种血糖反应的减弱是由于刺激的Ra降低（P＜0.05），而不是由于Rd增加。IRI的变化与血糖反应的降低平行。因此，吲哚美辛和水杨酸盐均通过减弱葡萄糖生成而非增强葡萄糖利用或胰岛素分泌来减弱对胰高血糖素和胰高血糖素加肾上腺素的血糖反应。这两种前列腺素合成抑制剂的结果表明前列腺素调节胰高血糖素和肾上腺素的肝脏作用。
