Saha Joy K, Xia Jinqi, Grondin Janet M, Engle Steven K, Jakubowski Joseph A
Eli Lilly and Company, BioTDR, DC 0444, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Exp Biol Med (Maywood). 2005 Nov;230(10):777-84. doi: 10.1177/153537020523001012.
The effects of anesthetic agents, commonly used in animal models, on blood glucose levels in fed and fasted rats were investigated. In fed Sprague-Dawley rats, ketamine (100 mg/kg)/xylazine (10 mg/kg) (KX) produced acute hyperglycemia (blood glucose 178.4 +/- 8.0 mg/dl) within 20 min. The baseline blood glucose levels (104.8 +/- 5.7 mg/dl) reached maximum levels (291.7 +/- 23.8 mg/dl) at 120 min. Ketamine alone did not elevate glucose levels in fed rats. Isoflurane also produced acute hyperglycemia similar to KX. Administration of pentobarbital sodium did not produce hyperglycemia in fed rats. In contrast, none of these anesthetic agents produced hyperglycemia in fasted rats. The acute hyperglycemic effect of KX in fed rats was associated with decreased plasma levels of insulin, adrenocorticotropic hormone (ACTH), and corticosterone and increased levels of glucagon and growth hormone (GH). The acute hyperglycemic response to KX was dose-dependently inhibited by the specific alpha2-adrenergic receptor antagonist yohimbine (1-4 mg/kg). KX-induced changes of glucoregulatory hormone levels such as insulin, GH, ACTH, and corticosterone were significantly altered by yohimbine, whereas the glucagon levels remained unaffected. In conclusion, the present study indicates that both KX and isoflurane produce acute hyperglycemia in fed rats. The effect of KX is mediated by modulation of the glucoregulatory hormones through stimulation of alpha2-adrenergic receptors. Pentobarbital sodium did not produce hyperglycemia in either fed or fasted rats. Based on these findings, it is suggested that caution needs to be taken when selecting anesthetic agents, and fed or fasted state of animals in studies of diabetic disease or other models where glucose and/or glucoregulatory hormone levels may influence outcome and thus interpretation. However, fed animals are of value when exploring the hyperglycemic response to anesthetic agents.
研究了动物模型中常用麻醉剂对喂食和禁食大鼠血糖水平的影响。在喂食的斯普拉格-道利大鼠中，氯胺酮（100毫克/千克）/赛拉嗪（10毫克/千克）（KX）在20分钟内产生急性高血糖（血糖178.4±8.0毫克/分升）。基线血糖水平（104.8±5.7毫克/分升）在120分钟时达到最高水平（291.7±23.8毫克/分升）。单独使用氯胺酮不会提高喂食大鼠的血糖水平。异氟醚也产生了与KX相似的急性高血糖。戊巴比妥钠给药未在喂食大鼠中产生高血糖。相比之下，这些麻醉剂在禁食大鼠中均未产生高血糖。KX在喂食大鼠中的急性高血糖作用与血浆胰岛素、促肾上腺皮质激素（ACTH）和皮质酮水平降低以及胰高血糖素和生长激素（GH）水平升高有关。KX引起的急性高血糖反应被特异性α2-肾上腺素能受体拮抗剂育亨宾（1-4毫克/千克）剂量依赖性抑制。育亨宾显著改变了KX诱导的胰岛素、GH、ACTH和皮质酮等糖调节激素水平的变化，而胰高血糖素水平未受影响。总之，本研究表明KX和异氟醚均在喂食大鼠中产生急性高血糖。KX的作用是通过刺激α2-肾上腺素能受体调节糖调节激素介导的。戊巴比妥钠在喂食或禁食大鼠中均未产生高血糖。基于这些发现，建议在选择麻醉剂时要谨慎，并且在糖尿病疾病研究或其他葡萄糖和/或糖调节激素水平可能影响结果并因此影响解释的模型中，要考虑动物的喂食或禁食状态。然而，在探索对麻醉剂的高血糖反应时，喂食动物具有价值。
