Reduced Expression of PLCXD3 Associates With Disruption of Glucose Sensing and Insulin Signaling in Pancreatic β-Cells

Abstract

Previous work has shown that reduced expression of <i>PLCXD3</i>, a member of the phosphoinositide-specific phospholipases (PI-PLC) family, impaired insulin secretion with an unclear mechanism. In the current study, we aim to investigate the mechanism underlying this effect using human islets and rat INS-1 (832/13) cells. Microarray and RNA sequencing data showed that <i>PLCXD3</i> is among the highly expressed PI-PLCs in human islets and INS-1 (832/13) cells. Expression of <i>PLCXD3</i> was reduced in human diabetic islets, correlated positively with <i>Insulin</i> and <i>GLP1R</i> expression and inversely with the donor's body mass index (BMI) and glycated hemoglobin (HbA_1c). Expression silencing of <i>PLCXD3</i> in INS-1 (832/13) cells was found to reduce glucose-stimulated insulin secretion (GSIS) and insulin content. In addition, the expression of <i>Insulin, NEUROD1, GLUT2, GCK, INSR, IRS2</i>, and <i>AKT</i> was downregulated. Cell viability and apoptosis rate were unaffected. In conclusion, our data suggest that low expression of <i>PLCXD3</i> in pancreatic β-cells associates with downregulation of the key insulin signaling and insulin biosynthesis genes as well as reduction in glucose sensing.