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

Hayat Aljaibeji; Debasmita Mukhopadhyay; Abdul Khader Mohammed; Sarah Dhaiban; Mahmood Y Hachim; Noha M Elemam; Nabil Sulaiman; Albert Salehi; Jalal Taneera

doi:10.3389/fendo.2019.00735

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

Front Endocrinol (Lausanne). 2019 Nov 6:10:735. doi: 10.3389/fendo.2019.00735. eCollection 2019.

Authors

Hayat Aljaibeji¹, Debasmita Mukhopadhyay¹, Abdul Khader Mohammed¹, Sarah Dhaiban¹, Mahmood Y Hachim¹, Noha M Elemam¹, Nabil Sulaiman¹, Albert Salehi², Jalal Taneera¹

Affiliations

¹ Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
² Department of Clinical Sciences, Lund University Diabetes Centre (LUDC), Lund University, Malmö, Sweden.

Abstract

Previous work has shown that reduced expression of PLCXD3, 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 PLCXD3 is among the highly expressed PI-PLCs in human islets and INS-1 (832/13) cells. Expression of PLCXD3 was reduced in human diabetic islets, correlated positively with Insulin and GLP1R expression and inversely with the donor's body mass index (BMI) and glycated hemoglobin (HbA_1c). Expression silencing of PLCXD3 in INS-1 (832/13) cells was found to reduce glucose-stimulated insulin secretion (GSIS) and insulin content. In addition, the expression of Insulin, NEUROD1, GLUT2, GCK, INSR, IRS2, and AKT was downregulated. Cell viability and apoptosis rate were unaffected. In conclusion, our data suggest that low expression of PLCXD3 in pancreatic β-cells associates with downregulation of the key insulin signaling and insulin biosynthesis genes as well as reduction in glucose sensing.

Keywords: PLCXD3; RNA sequencing; gene expression; microarray; type 2 diabetes.