Ishiwata Yasuyoshi, Sanada Yasuaki, Yasuhara Masato
Department of Hospital Pharmacy, School of Medicine, Tokyo Medical and Dental University, Japan.
Biol Pharm Bull. 2006 Mar;29(3):527-31. doi: 10.1248/bpb.29.527.
To clarify the mechanisms of gatifloxacin (GFLX)-induced hypoglycemia and hyperglycemia, the effect of GFLX on serum glucose levels was investigated in normal and diabetic rats. Rats received an intravenous injection of GFLX and their arterial blood was sampled periodically. Diabetic rats were produced by the intraperitoneal injection of streptozotocin and nicotinamide. In normal rats, the serum glucose concentration was decreased by GFLX at 25 and 50 mg/kg, while it was elevated 0.25 h after the injection of 100 mg/kg of GFLX. Serum immunoreactive insulin (IRI) levels increased as the dose of GFLX increased. The serum epinephrine concentration rose rapidly after the injection of GFLX at 50 and 100 mg/kg. In diabetic rats, the serum glucose concentration was actually increased by GFLX at 50 mg/kg. The baseline concentration of IRI was lower and the degree of the elevation caused by GFLX was smaller in diabetic rats. Both diabetic and control rats showed an increase in the serum epinephrine concentration after the injection of 50 mg/kg of GFLX. In conclusion, GFLX-induced secretion of insulin and epinephrine would contribute to the abnormalities in glucose homeostasis. The response of serum glucose to GFLX may differ between diabetic and normal rats due to the alteration of insulin secretion.
为阐明加替沙星（GFLX）诱导低血糖和高血糖的机制，研究了GFLX对正常大鼠和糖尿病大鼠血清葡萄糖水平的影响。大鼠接受静脉注射GFLX，并定期采集动脉血样。糖尿病大鼠通过腹腔注射链脲佐菌素和烟酰胺制成。在正常大鼠中，25和50mg/kg的GFLX可降低血清葡萄糖浓度，而注射100mg/kg的GFLX后0.25小时血清葡萄糖浓度升高。血清免疫反应性胰岛素（IRI）水平随GFLX剂量增加而升高。注射50和100mg/kg的GFLX后，血清肾上腺素浓度迅速上升。在糖尿病大鼠中，50mg/kg的GFLX实际上会使血清葡萄糖浓度升高。糖尿病大鼠的IRI基线浓度较低，GFLX引起的升高程度较小。注射50mg/kg的GFLX后，糖尿病大鼠和对照大鼠的血清肾上腺素浓度均升高。总之，GFLX诱导的胰岛素和肾上腺素分泌会导致葡萄糖稳态异常。由于胰岛素分泌的改变，糖尿病大鼠和正常大鼠血清葡萄糖对GFLX的反应可能不同。
