title: Hydrogen sulphide reduces insulin secretion from HIT-T15 cells by a KATP channel-dependent pathway.
abstract: Hydrogen sulphide (H(2)S), a naturally occurring gas exerts physiological effects by opening K(ATP) channels. Anti-diabetic drugs (e.g. glibenclamide) block K(ATP) channels and abrogate H(2)S-mediated physiological responses which suggest that H(2)S may also regulate insulin secretion by pancreatic beta-cells. To investigate this hypothesis, insulin-secreting (HIT-T15) cells were exposed to NaHS (100 microM) 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 microM). 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 Ca(2+) channels. This subsequently prevents Ca(2+) influx and the release of insulin from HIT-T15 cells. This data suggest that H(2)S reduces insulin secretion by a K(ATP) channel-dependent pathway in HIT-T15 cells. This study reports the molecular mechanism by which H(2)S reduces insulin secretion and provides further insight into a recent observation of increased pancreatic H(2)S production in streptozotocin-diabetic rats.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Muhammed Yusuf
authors.initials: MY
authors.lastname: Ali
authors.forename: Matthew
authors.initials: M
authors.lastname: Whiteman
authors.forename: Chian-Ming
authors.initials: CM
authors.lastname: Low
authors.forename: Philip K
authors.initials: PK
authors.lastname: Moore
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D003864:Depression, Chemical; D004594:Electrophysiology; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000032:analysis / Q000378:metabolism*; D000078790:Insulin Secretion; D015640:Ion Channel Gating / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D054086:KATP Channels / Q000187:drug effects*; D049449:Luminescence; D008856:Microscopy, Fluorescence; D011188:Potassium / Q000032:analysis / Q000378:metabolism; D051381:Rats
chemical_list: D015220:Calcium Channels; D007004:Hypoglycemic Agents; D007328:Insulin; D054086:KATP Channels; D000255:Adenosine Triphosphate; D005978:Glutathione; D011188:Potassium; D005905:Glyburide; D002118:Calcium; D006862:Hydrogen Sulfide