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¹ Departments of Pharmacology and
² Biochemistry, Cardiovascular Biology Research Group, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore, Singapore 117456
³ Peninsula Medical School, Universities of Exeter and Plymouth, St Luke’s Campus, Magdalen Road, Exeter EX1 2LU, England, UK

(Correspondence should be addressed to P K Moore; Email: phchead{at}nus.edu.sg)

Hydrogen sulphide (H₂S), a naturally occurring gas exerts physiological effects by opening K_ATP channels. Anti-diabetic drugs (e.g. glibenclamide) block K_ATP channels and abrogate H₂S-mediated physiological responses which suggest that H₂S may also regulate insulin secretion by pancreatic ß-cells. To investigate this hypothesis, insulin-secreting (HIT-T15) cells were exposed to NaHS (100 µM) and the K_ATP 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 K_ATP 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.