title: [Influence of tacrolimus and ciprofloxacin on glucose metabolism].
abstract: Tacrolimus is an immunosuppressive drug that causes glucose intolerance. On the other hand, ciprofloxacin, which is widely used in the treatment of infectious diseases, is known to cause hypoglycemia as a side effect. We investigated the effects of tacrolimus and ciprofloxacin 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 ciprofloxacin 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 ciprofloxacin, and the insulin level in the supernatant was measured. Ciprofloxacin did not show a significant effect 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 ciprofloxacin 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 ciprofloxacin 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 significant difference in insulin secretion. These results suggest that the cytotoxic effects of ciprofloxacin and tacrolimus cause a decrease in insulin secretion, leading to glucose intolerance.
authors.affiliation: Faculty of Pharmaceutical Science, Hiroshima International University, Hirokoshingai, Kure City, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tayama
authors.forename: Katsushi
authors.initials: K
authors.lastname: Miyake
authors.forename: Takami
authors.initials: T
authors.lastname: Nagafuji
authors.forename: Takako
authors.initials: T
authors.lastname: Gouhara
authors.forename: Shushi
authors.initials: S
authors.lastname: Morita
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Arai
authors.forename: Eiji
authors.initials: E
authors.lastname: Sato
authors.forename: Teruaki
authors.initials: T
authors.lastname: Kitaura
authors.forename: Kenji
authors.initials: K
authors.lastname: Kihira
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000009:adverse effects* / Q000494:pharmacology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000139:chemically induced*; D007003:Hypoglycemia / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D007166:Immunosuppressive Agents; D007328:Insulin; D002939:Ciprofloxacin; D005947:Glucose; D016559:Tacrolimus