Introduction: Ferulic acid is a natural polyphenol richly found in rice bran, whole grains and citrus fruits. Studies showed that this compound induced in vitro insulin secretion and decreased blood glucose in diabetic animal model. Aims: To study the effects of ferulic acid on cell viability, L-type Ca2+ channel, and insulin secretion, in INS-1 cells, a rat insulinoma cell line. Methods: Cell viability was assessed with MTT assay. Whole-cell L-type Ca2+ currents were recorded using patch clamp technique. Insulin secretion was measured with ELISA assay. Results: INS-1 cells exposure to 0.3–100 µM ferulic acid for 24 and 48 hours did not affect the cell viability. Electrophysiological experiments showed that ferulic acid significantly induced a rapid concentration-dependent increase in L-type Ca2+ currents (mean ± SEM; EC50, 3.10 ± 0.22 µM; maximum increase, 70.98 ± 9.64%). Moreover, 10 µM ferulic acid shifted the conductance-voltage curve in the hyperpolarized direction (control vs. ferulic acid: V½, -15.16 ± 2.11 vs. -20.75 ± 2.97 mV, n = 7, p = 0.03, paired t-test), with decreased slope factor (8.56 ± 0.74 vs. 6.21 ± 0.35 mV, n = 7, p = 0.02, paired t-test), while the voltage dependence of inactivation was not affected. Furthermore, 10 µM ferulic acid could significantly increase insulin secretion and this effect was inhibited by nifedipine and Ca2+-free extracellular fluid: %Increase of insulin secretion in cells treated with ferulic acid, ferulic acid + nifedipine, and ferulic acid in Ca2+-free solution were 41.79 ± 1.46%, 1.93 ± 5.34%, and -3.96 ± 3.18%, respectively (n = 3 each, p < 0.05, one-way ANOVA with Tukey’s post hoc test). Conclusion: We demonstrated that ferulic acid-induced insulin secretion in INS-1 cells was mediated by augmenting Ca2+ influx through L-type Ca2+ channel. This is the first electrophysiological demonstration that acute ferulic acid exposure could increase L-type Ca2+ current by enhancing the channel’s voltage sensitivity, which may explain the rapid ferulic acid-induced insulin secretion and in vivo lowering of blood glucose levels. No conflict of interest.
Physiology 2021 (2021) Proc Physiol Soc 48, PC092
Poster Communications: Ferulic acid enhanced L-type Ca2+ channel function and insulin secretion in rat insulinoma cell line
Katesirin Ruamyod1, Wattana Watanapa1, Pimchanok Nambandit1, Chanrit Kakhai1, Sukrit Treewaree1, Parin Wongsanupa1
1 Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Where applicable, experiments conform with Society ethical requirements.