Endogenous hydrogen sulfide protects pancreatic beta-cells from a high-fat diet-induced glucotoxicity and prevents the development of type 2 diabetes

Mitsuhiro Okamoto, Mami Yamaoka, Masahiro Takei, Tomomi Ando, Shigeki Taniguchi, Isao Ishii, Kazuo Tohya, Toshimasa Ishizaki, Ichiro Niki, Toshihide Kimura

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)227-233
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume442
Issue number3-4
DOIs
Publication statusPublished - 2013 Dec 13

Keywords

  • CSE
  • Cell protection
  • Hydrogen sulfide
  • Pancreatic beta-cells
  • TBP-2
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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