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

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

JOURNAL=Frontiers in Endocrinology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00735

DOI=10.3389/fendo.2019.00735

ISSN=1664-2392

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