title: Gatifloxacin acutely stimulates insulin secretion and chronically suppresses insulin biosynthesis.
abstract: 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.
authors.affiliation: Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Chizumi
authors.initials: C
authors.lastname: Yamada
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nagashima
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ueno
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D045744:Cell Line, Tumor; D002469:Cell Separation; D024841:Fluoroquinolones / Q000494:pharmacology*; D000077734:Gatifloxacin; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism*; D007329:Insulin Antagonists; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D000890:Anti-Infective Agents; D001786:Blood Glucose; D024841:Fluoroquinolones; D007004:Hypoglycemic Agents; D007328:Insulin; D007329:Insulin Antagonists; D015363:Quinolones; D012333:RNA, Messenger; D000077734:Gatifloxacin; D005905:Glyburide