文摘
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 is to examine the effects of hydrogen sulfide on the onset and development of type 2 diabetes. Middle-aged wild-type (WT) and CSE knockout (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. After 8 weeks of HFD, blood glucose levels were markedly increased in middle-aged KO mice, insulin responses were significantly reduced, and DNA fragmentation of the islet cells was increased. In order to assess the effects of HFD on 6-month-old mice, we analyzed changes in gene expression in the islets. As a result, we found that expression of thioredoxin binding protein-2 (TBP-2, also known as Txnip) was increased in middle-aged KO mice. Administration of NaHS (a hydrogen sulfide donor) reduced TBP-2 gene levels in isolated islets from KO mice. The 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.