Glucose-induced production of hydrogen sulfide may protect the pancreatic beta-cells from apoptotic cell death by high glucose.
We examined the expression of the major H(2)S-producing enzymes, cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE). CBS was ubiquitously distributed in the mouse pancreas, but CSE was found only in the exocrine. Freshly isolated islets expressed CBS, while CSE was faint. However, high glucose increased the CSE expression in the beta-cells. L-Cysteine or NaHS suppressed islet cell apoptosis with high glucose, and increased glutathione content in MIN6 beta-cells. Pretreatment with L-cysteine improved the secretory responsiveness following stimulation with glucose. The CSE inhibitor DL-propargylglycine antagonized these L-cysteine effects. We suggest H(2)S may function as an 'intrinsic brake' which protects beta-cells from glucotoxicity.
Kaneko
Yukiko
Y
Department of Pharmacology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Oita 879-5593, Japan.
Kimura
Toshihide
T
Taniguchi
Shigeki
S
Souma
Midori
M
Kojima
Yumiko
Y
Kimura
Yuka
Y
Kimura
Hideo
H
Niki
Ichiro
I
D000818:Animals; D017209:Apoptosis; D003541:Cystathionine beta-Synthase / Q000096:biosynthesis*; D003542:Cystathionine gamma-Lyase / Q000096:biosynthesis*; D003545:Cysteine / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D013440:Sulfides / Q000494:pharmacology
D013440:Sulfides; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D005947:Glucose; D003545:Cysteine; D006862:Hydrogen Sulfide