Tacrolimus is an immunosuppressive drug that causes glucose intolerance. On the other hand, cipro‰oxacin, which is widely used in the treatment of infectious diseases, is known to cause hypoglycemia as a side eŠect. We investigated the eŠects of tacrolimus and cipro‰oxacin on serum glucose and insulin levels in rats, as well as on insulin secretion and the viability of HIT-T15 cells. The rats received intraperitoneal injections of tacrolimus and/or cipro‰oxacin for 1 week, and their arterial blood was sampled after the administration of glucose. HIT-T15 cells were cultured in the presence of tacrolimus and/or cipro‰oxacin, and the insulin level in the supernatant was measured. Cipro‰oxacin did not show a signiˆcant eŠect on serum glucose and insulin levels after multiple administrations in the rats. In contrast, rats in the tacrolimus treatment group showed low serum insulin and high serum glucose levels. Moreover, the coadministration of cipro‰oxacin and tacrolimus resulted in higher glucose levels compared with tacrolimus alone 0.5 h after glucose stimulation. In addition, we observed that the rats administered tacrolimus and/or cipro‰oxacin had low body weight and food intake. Tacrolimus caused a dose-dependent decrease in the viability of the HIT-T15 cells. Furthermore, both drugs were highly toxic to HIT-T15 cells. In contrast, tacrolimus alone and coadministration of the drugs resulted in no signiˆcant diŠerence in insulin secretion. These results suggest that the cytotoxic eŠects of cipro‰oxacin and tacrolimus cause a decrease in insulin secretion, leading to glucose intolerance.
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