The Mechanisms of Insulin Secretion and Calcium Signaling in Pancreatic β-Cells Exposed to Fluoroquinolones
Open accessAbstract
Fluoroquinolones reportedly induce hypoglycemia through stimulation of insulin secretion from pancreatic β-cells via inhibition of K(ATP) channels and activation of L-type voltage-dependent Ca(2+) channels. In physiological condition, the cytosolic Ca(2+) concentration ([Ca(2+)](c)) is also regulated by release of Ca(2+) from intracellular Ca(2+) stores. In this study, we investigated the mechanism of insulin secretion induced by fluoroquinolones, with respect to intracellular Ca(2+) stores. Even where the absence of supplemental extracellular Ca(2+), insulin secretion and [Ca(2+)](c) were increased by gatifloxacin, levofloxacin or tolbutamide. Insulin secretion and the rise of [Ca(2+)](c) induced by fluoroquinolones were reduced by depleting of Ca(2+) 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 [Ca(2+)](c). Destruction of acidic Ca(2+) stores such as lysosome and lysosome-related organelles by glycyl-L-phenylalanine-2-nephthylamide (GPN) did not affect insulin secretion and the rise of [Ca(2+)](c) induced by fluoroquinolones. The increase in insulin and [Ca(2+)](c) induced by tolbutamide were reduced by thapsigargin, dantrolene, and GPN but not by xestospongin C. In conclusion, fluoroquinolones induces Ca(2+) release from ER mediated by the ryanodine receptor, and the reaction might involve in insulin secretion. Sulfonylureas induce Ca(2+) release from GPN-sensitive acidic Ca(2+) stores, but fluoroquinolones did not.
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Clinafloxacin and gatifloxacin cause hypoglycemia via β-cell KATP channel inhibition.
“β -cell K ATP channel inhibition [105].”
From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [105]
The Abstract (page unavailable) reports that fluoroquinolones can cause hypoglycemia through β-cell KATP-channel inhibition, and the Results identify gatifloxacin as stimulating insulin secretion. The copy does not mention clinafloxacin, so it does not support that drug-specific part of the claim. (LLM, conf=0.88)
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Non-Diabetic Hypoglycemia: Evaluation and Management in Adults
Looi, E., & Lawler, H. M. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14134393 · Cited by 10 · see citing works
“Not usually seen in adults, and may even cause hyperglycemia [104] Clinafloxacin and Gatifloxacin Fluroquinolone β -cell K ATP channel inhibition [105].”
- Authors
- Bito, M., Tomita, T., Komori, M., Taogoshi, T., Kimura, Y., & Kihira, K.
- Affiliations
- Hiroshima University (JP)
- Venue
- Biological and Pharmaceutical Bulletin
- Publisher
- Pharmaceutical Society of Japan
- Published
- 2013
- Volume
- 36
- Issue
- 1
- Pages
- 31-35
- ISSN
- 0918-6158 (ISSN-L)
- 1347-5215
- OpenAlex
- W1986014140
- Cited by
- 20
- References
- 0
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 2 · 2021: 1 · 2019: 2 · 2017: 4 · 2016: 1 · 2015: 2 · 2013: 1
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Biological and Pharmaceutical Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- fluoroquinolones, insulin secretion, pancreatic beta cells, calcium signaling, endoplasmic reticulum calcium stores, ryanodine receptor, IP3 receptor, tolbutamide, gatifloxacin, levofloxacin, thapsigargin, dantrolene, xestospongin C, sulfonylureas, hypoglycemia
- MeSH terms
- Gatifloxacin, Insulin Secretion, Animals, Anti-Bacterial Agents, Cell Line, Cricetinae, Insulin, Tolbutamide, Ofloxacin, Calcium Signaling, Fluoroquinolones, Insulin-Secreting Cells, Levofloxacin
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