Endoplasmic reticulum stress (ER), which plays a key role in oxidative stress, is a common cause of β-cell apoptosis and dysfunction in type 2 diabetes mellitus, involving decreased insulin secretory response and a reduction in β-cell mass. Particular attention has been paid to improvement of type 2 diabetes mellitus induced by the naturally-occurring polyphenol– known as flavonoids, due to their broad biological activities. However, there is a dearth of information about the effect of the trihydroxyflavone apigenin, on pancreatic β-cell functions.
In this study, we investigated the effect of apigenin on glucose-induced insulin secretion (GSIS) and β-cell apoptosis, studying the mechanism underlying its anti-diabetic effects, using INS-ID β-cell line. The results showed that apigenin dose-dependently stimulated GSIS at all doses (1,10, 30 & 100 μM), with significant peak effect at 30 μM concentration. The downstream ER stress signaling proteins, CHOP and Cleaved caspase-3, which were elevated by thapsigargin-induced apoptosis of INS-1 cells, were significantly, concentration dependently and strongly attenuated by apigenin treatment at all doses, with peak suppression at concentrations of 30 and 100 μM. These results were strongly correlated with DNA fragmentation, indicative of apoptosis, as determined by DNA laddering.
Taken together, these results suggest that apigenin is an attractive candidate with remarkable and potent insulinotropic and anti-apoptotic effects on β-cells, and that its anti-diabetic effect may be mediated by increasing GSIS and preventing ER stress-mediated β-cell apoptosis mediated by CHOP and cleaved caspase-3, hence promoting β-cells survival and function.