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

Biochem Biophys Res Commun. 2013 Dec 13;442(3-4):227-33. doi: 10.1016/j.bbrc.2013.11.023. Epub 2013 Nov 15.


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 8weeks. 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 8weeks 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.

Keywords: ATP-sensitive K(+); CAT; CBS; CO; CSE; Cell protection; ChREBP; DAO; HFD; Hydrogen sulfide; K(ATP); NO; PPG; Pancreatic beta-cells; STZ; TBP-2; Type 2 diabetes mellitus; carbohydrate response element-binding protein; carbon monoxide; cystathionine beta-synthase; cystathionine gamma-lyase; cysteine aminotransferase; d-amino acid oxidase; dl-propargylglycine; high-fat diet; nitric oxide; streptozotocin; thioredoxin binding protein-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Cystathionine gamma-Lyase / genetics
  • Cytoprotection*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology*
  • Diet, High-Fat / adverse effects*
  • Gene Expression
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Hydrogen Sulfide / metabolism*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology*
  • Mice
  • Mice, Knockout
  • Thioredoxins / genetics


  • Carrier Proteins
  • Txnip protein, mouse
  • Thioredoxins
  • Cystathionine gamma-Lyase
  • Glucose
  • Hydrogen Sulfide