Hydrogen sulphide (H2S), a naturally occurring gas exerts physiological effects by opening KATP channels. Anti-diabetic drugs (e.g. glibenclamide) block KATP channels and abrogate H2S-mediated physiological responses which suggest that H2S may also regulate insulin secretion by pancreatic β-cells. To investigate this hypothesis, insulin-secreting (HIT-T15) cells were exposed to NaHS (100 μM) and the KATP channel-driven pathway of insulin secretion was tracked with various fluorescent probes. The concentration of insulin released from HIT-T15 cells decreased significantly after NaHS exposure and this effect was reversed by the addition of glibenclamide (10 μM). Cell viability and intracellular ATP and glutathione (GSH) levels remained unchanged, suggesting that changes in insulin secretion were not ATP linked or redox dependent. Through fluorescence imaging studies, it was found that K+ efflux occurs in cells exposed to NaHS. The hyperpolarised cell membrane, a result of K+ leaving the cell, prevents the opening of voltage-gated Ca2+ channels. This subsequently prevents Ca2+ influx and the release of insulin from HIT-T15 cells. This data suggest that H2S reduces insulin secretion by a KATP channel-dependent pathway in HIT-T15 cells. This study reports the molecular mechanism by which H2S reduces insulin secretion and provides further insight into a recent observation of increased pancreatic H2S production in streptozotocin-diabetic rats.
Hydrogen sulphide reduces insulin secretion from HIT-T15 cells by a KATP channel-dependent pathway