title: Gatifloxacin induces augmented insulin release and intracellular insulin depletion of pancreatic islet cells.
abstract: Many hypoglycemic and hyperglycemic episodes associated with clinical use of gatifloxacin (GFLX), a novel fluoroquinolone antimicrobial agent, have been reported in recent years. Some have reported hypoglycemia induced by fluoroquinolones, indicating that these agents may stimulate insulin secretion from pancreatic islet cells. In this study, we investigated the effect of GFLX on insulin homeostasis in islet cells using the insulin secreting cell line, HIT-T15. After 1 h incubation with over 100 microM of GFLX, insulin secretion from the cells was significantly augmented. However, the augmentation of insulin release induced by GFLX subsequently reached a plateau. Coincidentally, cellular insulin was decreased by 120 h incubation, and reactivity to re-stimulation by sulfonylurea was suppressed. The GFLX insulin depletion effect was stronger than the effects produced by such other fluoroquinolones as levofloxacin and ciprofloxacin. This study suggests that GFLX should induce insulin oversecretion from pancreatic islet cells in the short-term, and decrease insulin productivity or increase insulin disintegration in the long-term. These results are consistent with the clinical results of GFLX finding that hypoglycemic episodes were seen after a first single administration, and most hyperglycemic episodes were seen more than 2 d after the start of administration.
authors.affiliation: Department of Pharmaceutical Services, Hiroshima University Hospital, Japan. ttomita@hiroshima-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Tomita
authors.forename: Mariko
authors.initials: M
authors.lastname: Onishi
authors.forename: Eiji
authors.initials: E
authors.lastname: Sato
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kenji
authors.initials: K
authors.lastname: Kihira
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones / Q000494:pharmacology*; D000077734:Gatifloxacin; D007004:Hypoglycemic Agents / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008647:Mesocricetus
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D007004:Hypoglycemic Agents; D007328:Insulin; D000077734:Gatifloxacin