Glycolytic enzyme Enolase-1 regulates insulin gene expression in pancreatic β-cell

Biochem Biophys Res Commun. 2024 Apr 30:706:149735. doi: 10.1016/j.bbrc.2024.149735. Epub 2024 Feb 28.

Abstract

Enolase-1 (Eno1) plays a critical role in regulating glucose metabolism; however, its specific impact on pancreatic islet β-cells remains elusive. This study aimed to provide a preliminary exploration of Eno1 function in pancreatic islet β-cells. The findings revealed that the expression of ENO1 mRNA in type 2 diabetes donors was significantly increased and positively correlated with HbA1C and negatively correlated with insulin gene expression. A high level of Eno1 in human insulin-secreting rat INS-1832/13 cells with co-localization with intracellular insulin proteins was accordingly observed. Silencing of Eno1 using siRNA or inhibiting Eno1 protein activity with an Eno1 antagonist significantly reduced insulin secretion and insulin content in β-cells, while the proinsulin/insulin content ratio remained unchanged. This reduction in β-cells function was accompanied by a notable decrease in intracellular ATP and mitochondrial cytochrome C levels. Overall, our findings confirm that Eno1 regulates the insulin secretion process, particularly glucose metabolism and ATP production in the β-cells. The mechanism primarily involves its influence on insulin production, suggesting that Eno1 represents a potential target for β-cell protection and diabetes treatment.

Keywords: ATP; Enolase-1; Glucose metabolism; β-cells function.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Diabetes Mellitus, Type 2* / genetics
  • Diabetes Mellitus, Type 2* / metabolism
  • Gene Expression
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin-Secreting Cells* / metabolism
  • Phosphopyruvate Hydratase / genetics
  • Phosphopyruvate Hydratase / metabolism
  • Rats

Substances

  • Insulin
  • Phosphopyruvate Hydratase
  • Glucose
  • Adenosine Triphosphate
  • ENO1 protein, rat