Yamada Chizumi, Nagashima Kazuaki, Takahashi Akira, Ueno Hiroyuki, Kawasaki Yukiko, Yamada Yuichiro, Seino Yutaka, Inagaki Nobuya
Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Eur J Pharmacol. 2006 Dec 28;553(1-3):67-72. doi: 10.1016/j.ejphar.2006.09.043. Epub 2006 Sep 28.
Gatifloxacin can cause both hypoglycemia and hyperglycemia in both diabetic and non-diabetic patients. Gatifloxacin recently has been reported to stimulate insulin secretion by inhibition of ATP-sensitive K(+) (K(ATP)) channels in pancreatic beta-cells. Gatifloxacin-induced hypoglycemia is associated with concomitant use of sulfonylureas, and usually occurs immediately after administration of the drug. We find that gatifloxacin acutely stimulates insulin secretion from mouse pancreatic islets and that glibenclamide has additive effects on gatifloxacin-induced insulin secretion. On the other hand, gatifloxacin-induced hyperglycemia often takes several days to develop. We also demonstrate that chronic gatifloxacin treatment decreases islet insulin content by inhibiting insulin biosynthesis, which process may be associated with gatifloxacin-induced hyperglycemia. Moreover, discontinuation of gatifloxacin results in improved insulin secretory response. These data clarify the differing mechanisms of gatifloxacin-induced hyper- and hypoglycemia, and suggest that blood glucose levels should be carefully monitored during gatifloxacin administration, especially in elderly patients with renal insufficiency, unrecognized diabetes, or other metabolic disorders. Because the risk of potentially life-threatening dysglycemia is increased during gatifloxacin therapy, these findings have important implications for clinical practice.
加替沙星可在糖尿病和非糖尿病患者中引起低血糖和高血糖。最近有报道称，加替沙星通过抑制胰腺β细胞中的ATP敏感性钾（K(ATP)）通道来刺激胰岛素分泌。加替沙星诱导的低血糖与磺脲类药物的同时使用有关，通常在给药后立即发生。我们发现加替沙星可急性刺激小鼠胰岛分泌胰岛素，并且格列本脲对加替沙星诱导的胰岛素分泌有相加作用。另一方面，加替沙星诱导的高血糖通常需要数天时间才会出现。我们还证明，长期使用加替沙星会通过抑制胰岛素生物合成来降低胰岛胰岛素含量，这一过程可能与加替沙星诱导的高血糖有关。此外，停用加替沙星会导致胰岛素分泌反应改善。这些数据阐明了加替沙星诱导高血糖和低血糖的不同机制，并表明在使用加替沙星期间应仔细监测血糖水平，尤其是在患有肾功能不全、未被识别的糖尿病或其他代谢紊乱的老年患者中。由于在加替沙星治疗期间发生潜在危及生命的血糖异常的风险增加，这些发现对临床实践具有重要意义。
