TY - JOUR
T1 - Endogenous hydrogen sulfide protects pancreatic beta-cells from a high-fat diet-induced glucotoxicity and prevents the development of type 2 diabetes
AU - Okamoto, Mitsuhiro
AU - Yamaoka, Mami
AU - Takei, Masahiro
AU - Ando, Tomomi
AU - Taniguchi, Shigeki
AU - Ishii, Isao
AU - Tohya, Kazuo
AU - Ishizaki, Toshimasa
AU - Niki, Ichiro
AU - Kimura, Toshihide
N1 - Funding Information:
We are grateful to Y. Kaneko (University of Shizuoka), H. Yoshimatsu (Oita University) and L. Kang (Oita University) for helpful discussion. We would also like to thank M. Matsunaga, K. Tasaka and Y. Ueda for technical assistance. This research was supported by a KAKENHI Grant ( 21591146 ), the Oita Broadcasting System Cultural Foundation , and the Research Fund at the Discretion of the President, Oita University .
PY - 2013/12/13
Y1 - 2013/12/13
N2 - Chronic exposure to high glucose induces the expression of cystathionine gamma-lyase (CSE), a hydrogen sulfide-producing enzyme, in pancreatic beta-cells, thereby suppressing apoptosis. The aim of this study was to examine the effects of hydrogen sulfide on the onset and development of type 2 diabetes. Middle-aged (6-month-old) wild-type (WT) and CSE knockout (CSE-KO) mice were fed a high-fat diet (HFD) for 8 weeks. We determined the effects of CSE knockout on beta-cell function and mass in islets from these mice. We also analyzed changes in gene expression in the islets. After 8 weeks of HFD, blood glucose levels were markedly increased in middle-aged CSE-KO mice, insulin responses were significantly reduced, and DNA fragmentation of the islet cells was increased. Moreover, expression of thioredoxin binding protein-2 (TBP-2, also known as Txnip) was increased. Administration of NaHS, a hydrogen sulfide donor, reduced TBP-2 gene levels in isolated islets from CSE-KO mice. Gene levels were elevated when islets were treated with the CSE inhibitor dl-propargylglycine (PPG). These results provide evidence that CSE-produced hydrogen sulfide protects beta-cells from glucotoxicity via regulation of TBP-2 expression levels and thus prevents the onset/development of type 2 diabetes.
AB - Chronic exposure to high glucose induces the expression of cystathionine gamma-lyase (CSE), a hydrogen sulfide-producing enzyme, in pancreatic beta-cells, thereby suppressing apoptosis. The aim of this study was to examine the effects of hydrogen sulfide on the onset and development of type 2 diabetes. Middle-aged (6-month-old) wild-type (WT) and CSE knockout (CSE-KO) mice were fed a high-fat diet (HFD) for 8 weeks. We determined the effects of CSE knockout on beta-cell function and mass in islets from these mice. We also analyzed changes in gene expression in the islets. After 8 weeks of HFD, blood glucose levels were markedly increased in middle-aged CSE-KO mice, insulin responses were significantly reduced, and DNA fragmentation of the islet cells was increased. Moreover, expression of thioredoxin binding protein-2 (TBP-2, also known as Txnip) was increased. Administration of NaHS, a hydrogen sulfide donor, reduced TBP-2 gene levels in isolated islets from CSE-KO mice. Gene levels were elevated when islets were treated with the CSE inhibitor dl-propargylglycine (PPG). These results provide evidence that CSE-produced hydrogen sulfide protects beta-cells from glucotoxicity via regulation of TBP-2 expression levels and thus prevents the onset/development of type 2 diabetes.
KW - CSE
KW - Cell protection
KW - Hydrogen sulfide
KW - Pancreatic beta-cells
KW - TBP-2
KW - Type 2 diabetes mellitus
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U2 - 10.1016/j.bbrc.2013.11.023
DO - 10.1016/j.bbrc.2013.11.023
M3 - Article
C2 - 24246677
AN - SCOPUS:84890114693
SN - 0006-291X
VL - 442
SP - 227
EP - 233
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3-4
ER -
