Department of Hospital Pharmacy, School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Eur J Pharmacol. 2010 Oct 25;645(1-3):192-7. doi: 10.1016/j.ejphar.2010.07.032. Epub 2010 Jul 30.
Gatifloxacin, a fluoroquinolone antimicrobial agent, has been reported to cause both hypoglycemia and hyperglycemia in diabetic and non-diabetic patients. The purpose of the present study was to investigate the mechanism of gatifloxacin-induced hyperglycemia in normal and diabetic rats. Rats received a single intravenous injection of gatifloxacin and samples of their arterial blood were collected periodically. Diabetic rats were produced by the injection of streptozotocin and nicotinamide. In normal rats, the concentration of serum glucose decreased after the injection of gatifloxacin at 50mg/kg, while it increased with gatifloxacin at 100mg/kg. The concentrations of serum epinephrine and histamine increased after the injection of gatifloxacin at 100mg/kg. The increases in serum glucose and epinephrine concentrations were reduced by pretreatment with diphenhydramine at 1mg/kg. In diabetic rats, the concentration of serum glucose actually increased after the injection of gatifloxacin at 50mg/kg, concomitant with increases in the serum epinephrine and histamine concentrations. The concentration of serum immunoreactive insulin slightly increased after the injection of gatifloxacin at 50mg/kg. In addition, repeated oral administration of gatifloxacin to rats at 300 mg/kg twice a day for 7 days did not change glucose tolerance. In conclusion, gatifloxacin-induced release of histamine can contribute to an increase in the serum epinephrine concentration and hyperglycemia in normal rats. In diabetic rats, lower doses of gatifloxacin can induce hyperglycemia owing to the low level of insulin secretion that they exhibit compared with normal animals.
加替沙星是一种氟喹诺酮类抗菌药物，已被报道在糖尿病和非糖尿病患者中可引起低血糖和高血糖。本研究的目的是研究加替沙星在正常和糖尿病大鼠中引起高血糖的机制。大鼠接受单次静脉注射加替沙星，并定期采集动脉血样。糖尿病大鼠通过链脲佐菌素和烟酰胺注射产生。在正常大鼠中，在 50mg/kg 加替沙星注射后，血清葡萄糖浓度降低，而在 100mg/kg 加替沙星注射后升高。在 100mg/kg 加替沙星注射后，血清肾上腺素和组胺浓度增加。在用 1mg/kg 苯海拉明预处理后，血清葡萄糖和肾上腺素浓度的升高减少。在糖尿病大鼠中，在 50mg/kg 加替沙星注射后，血清葡萄糖浓度实际上升高，同时血清肾上腺素和组胺浓度升高。在 50mg/kg 加替沙星注射后，血清免疫反应性胰岛素浓度略有升高。此外，连续口服 300mg/kg 加替沙星，每天两次，连续 7 天，不会改变葡萄糖耐量。总之，加替沙星诱导的组胺释放可能导致正常大鼠血清肾上腺素浓度升高和高血糖。在糖尿病大鼠中，较低剂量的加替沙星可引起高血糖，这是由于它们与正常动物相比胰岛素分泌水平较低所致。
