The Mechanisms of Insulin Secretion and Calcium Signaling in Pancreatic β-Cells Exposed to Fluoroquinolones

DOI Web Site Web Site PubMed 被引用文献1件 参考文献14件
  • Bito Motoki
    Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University
  • Tomita Takashi
    Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University Department of Pharmaceutical Services, Hiroshima University Hospital
  • Komori Mika
    Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University
  • Taogoshi Takanori
    Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University Department of Pharmaceutical Services, Hiroshima University Hospital
  • Kimura Yasuhiro
    Department of Pharmaceutical Services, Hiroshima University Hospital Division of Clinical Pharmacotherapeutics, Graduate School of Biomedical Sciences, Hiroshima University
  • Kihira Kenji
    Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University Department of Pharmaceutical Services, Hiroshima University Hospital

この論文をさがす

抄録

Fluoroquinolones reportedly induce hypoglycemia through stimulation of insulin secretion from pancreatic β-cells via inhibition of KATP channels and activation of L-type voltage-dependent Ca2+ channels. In physiological condition, the cytosolic Ca2+ concentration ([Ca2+]c) is also regulated by release of Ca2+ from intracellular Ca2+ stores. In this study, we investigated the mechanism of insulin secretion induced by fluoroquinolones, with respect to intracellular Ca2+ stores. Even where the absence of supplemental extracellular Ca2+, insulin secretion and [Ca2+]c were increased by gatifloxacin, levofloxacin or tolbutamide. Insulin secretion and the rise of [Ca2+]c induced by fluoroquinolones were reduced by depleting of Ca2+ in endoplasmic reticumum (ER) by thapsigargin, and inhibiting ryanodine receptor of ER by dantrolene. Inhibition of inositol 1,4,5-triphosphate receptor of ER by xestospongin C suppressed insulin secretion induced by fluoroquinolones, whereas it did not affect [Ca2+]c. Destruction of acidic Ca2+ stores such as lysosome and lysosome-related organelles by glycyl-L-phenylalanine-2-nephthylamide (GPN) did not affect insulin secretion and the rise of [Ca2+]c induced by fluoroquinolones. The increase in insulin and [Ca2+]c induced by tolbutamide were reduced by thapsigargin, dantrolene, and GPN but not by xestospongin C. In conclusion, fluoroquinolones induces Ca2+ release from ER mediated by the ryanodine receptor, and the reaction might involve in insulin secretion. Sulfonylureas induce Ca2+ release from GPN-sensitive acidic Ca2+ stores, but fluoroquinolones did not.

収録刊行物

被引用文献 (1)*注記

もっと見る

参考文献 (14)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ