L-cysteine inhibits insulin release from the pancreatic β-cell -: Possible involvement of metabolic production of hydrogen sulfide, a novel gasotransmitter

被引:247
作者
Kaneko, Y
Kimura, Y
Kimura, H
Niki, I
机构
[1] Oita Univ, Fac Med, Dept Pharmacol, Oita 8795593, Japan
[2] Natl Inst Neurosci, Dept Mol Genet, Tokyo, Japan
关键词
D O I
10.2337/db05-1082
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Hydrogen sulfide (H2S) was historically recognized as a toxic gas generated by natural resources. However, its enzymatic production from L-cysteine has recently been demonstrated in mammals. Cystathionine beta-synthase and cystathionine gamma-lyase, both of which can produce H2S, were expressed in mouse pancreatic islet cells and the beta-cell line, MIN6. L-cysteine and the H,S donor NaHS inhibited glucose-induced insulin release from islets and MIN6 cells. These inhibitory effects were reproduced when insulin release was stimulated by alpha-ketoisocaproate, tolbutamide, or high K+. L-cysteine and NaHS inhibited glucose-potentiated insulin release in the copresence of diazoxide and high K+. Real-time imaging of intracellular Ca2+ concentration ([Ca2+]i) demonstrated that both L-Cysteine and NaHS reversibly suppressed glucose-induced [Ca2+](1) oscillation in a single P-cell without obvious changes in the mean value. These substances inhibited Ca2+-or guanosine 5'-0-3-thiotriphosphate-induced insulin release from islets permeabilized with streptolysin-O. L-Cysteine and NaHS reduced ATP production and attenuated glucose-induced hyperpolarization of the mitochondrial membrane potential. Finally, L-cysteine increased H2S content in MIN6 cells. We suggest here that L-cysteine inhibits insulin release via multiple actions on the insulin secretory process through H,S production. Because the activities of H2S-producing enzymes and the tissue H2S contents are known to increase under diabetic conditions, the inhibition may participate in the deterioration of insulin release in this disease.
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页码:1391 / 1397
页数:7
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