Hydrogen sulphide reduces insulin secretion from HIT-T15 cells by a KATP channel-dependent pathway

被引:75
作者
Ali, Muhammed Yusuf
Whiteman, Matthew
Low, Chian-Ming
Moore, Philip K.
机构
[1] Natl Univ Singapore, Yong Loo Lin Sch Med, Cardiovasc Biol Res Grp, Dept Pharmacol, Singapore 117456, Singapore
[2] Univ Exeter, Peninsula Med Sch, Exeter EX1 2LU, Devon, England
[3] Univ Plymouth, Exeter EX1 2LU, Devon, England
关键词
D O I
10.1677/JOE-07-0184
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Hydrogen sulphide (H,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 H2S-mediated physiological responses which suggest that H2S may also regulate insulin secretion by pancreatic beta-cells. To investigate this hypothesis, insulin-se cretin 9 (HIT-T15) cells were exposed to NaHS (100 mu M) 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 mu M). 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 H,S reduces insulin secretion by a K-ATP channel-dependent pathway in HIT-T15 cells. This study reports the molecular mechanism by which H,S reduces insulin secretion and provides further insight into a recent observation of increased pancreatic H2S production in streptozotocin-diabetic rats.
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页码:105 / 112
页数:8
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