Influence of Tacrolimus and Ciprofloxacin on Glucose Metabolism

Abstract

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.

Therapeutic Effect of an Immunomodulator on Pancreatic Endocrine Secretion Disorder and Insulitis in an Animal Model of Autoimmune Pancreatitis

“…However, in our study, while the body weight of each group was increased, the body weight in the pancreatitis group in which pancreatitis developed increased more than in the 1 mg group in which pancreatitis was suppressed . Tayama et al reported that FK506 administration induced hyperglycemia due to abnormality of glucose tolerance and that, as a consequence, the feeding center is suppressed, food intake decreases and body weight decreases 9 . It has also been suggested that other factors such as gastrointestinal disturbance and decreased absorption of food due to a decrease in intestinal ATP are involved 10 11 .…”