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Zafirlukast promotes insulin secretion by increasing calcium influx through L‐type calcium channels
Author(s) -
Hwang HyeonJeong,
Park KyoungSu,
Choi Jang Hyun,
Cocco Lucio,
Jang HyunJun,
Suh PannGhill
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26750
Subject(s) - zafirlukast , endocrinology , medicine , thapsigargin , chemistry , endoplasmic reticulum , insulin , calcium in biology , calcium , biology , receptor , antagonist , biochemistry
The zafirlukast has been reported to be anti‐inflammatory and widely used to alleviate the symptoms of asthma. However, its influence on insulin secretion in pancreatic β‐cells has not been investigated. Herein, we examined the effects of zafirlukast on insulin secretion and the potential underlying mechanisms. Among the cysteinyl leukotriene receptor 1 antagonists, zafirlukast, pranlukast, and montelukast, only zafirlukast enhanced insulin secretion in a concentration‐dependent manner in both low and high glucose conditions and elevated the level of [Ca 2+ ] i , further activating Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII), protein kinase B (AKT), and extracellular signal‐regulated kinase (ERK) signaling. These effects were nearly abolished by the L‐type Ca 2+ channel antagonist nifedipine, while treatment with thapsigargin, a sarco/endoplasmic reticulum Ca 2+ ATPase inhibitor, did not have the same effect, suggesting that zafirlukast primarily induces the entry of extracellular Ca 2+ rather than intracellular Ca 2+ from the endoplasmic reticulum. Zafirlukast treatment resulting in a significant drop in glucose levels and increased insulin secretion in C57BL/6J mice. These findings will contribute to an improved understanding of the side effects of zafirlukast and potential candidate for a therapeutic intervention in diabetes.