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

Enolase-1 (Eno1) plays a critical role in regulating glucose metabolism; however, its specific impact on pancreatic islet beta-cells remains elusive. This study aimed to provide a preliminary exploration of Eno1 function in pancreatic islet beta-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 beta-cells, while the proinsulin/insulin content ratio remained unchanged. This reduction in beta-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 beta-cells. The mechanism primarily involves its influence on insulin production, suggesting that Eno1 represents a potential target for beta-cell protection and diabetes treatment.