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

28 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
Externally publishedYes

Fingerprint

Hydrogen Sulfide
Insulin-Secreting Cells
High Fat Diet
Nutrition
Medical problems
Type 2 Diabetes Mellitus
Fats
Knockout Mice
Genes
Cystathionine gamma-Lyase
DNA Fragmentation
Islets of Langerhans
Gene expression
Blood Glucose
Insulin
Apoptosis
Gene Expression
Glucose
DNA
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Endogenous hydrogen sulfide protects pancreatic beta-cells from a high-fat diet-induced glucotoxicity and prevents the development of type 2 diabetes. / Okamoto, Mitsuhiro; Yamaoka, Mami; Takei, Masahiro; Ando, Tomomi; Taniguchi, Shigeki; Ishii, Isao; Tohya, Kazuo; Ishizaki, Toshimasa; Niki, Ichiro; Kimura, Toshihide.

In: Biochemical and Biophysical Research Communications, Vol. 442, No. 3-4, 13.12.2013, p. 227-233.

Research output: Contribution to journalArticle

Okamoto, Mitsuhiro ; Yamaoka, Mami ; Takei, Masahiro ; Ando, Tomomi ; Taniguchi, Shigeki ; Ishii, Isao ; Tohya, Kazuo ; Ishizaki, Toshimasa ; Niki, Ichiro ; Kimura, Toshihide. / Endogenous hydrogen sulfide protects pancreatic beta-cells from a high-fat diet-induced glucotoxicity and prevents the development of type 2 diabetes. In: Biochemical and Biophysical Research Communications. 2013 ; Vol. 442, No. 3-4. pp. 227-233.
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