Reduced Expression of PLCXD3 Associates With Disruption of Glucose Sensing and Insulin Signaling in Pancreatic β-Cells
Reduced Expression of PLCXD3 Associates With Disruption of Glucose Sensing and Insulin Signaling in Pancreatic β-Cells
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DOI：
10.3389/fendo.2019.00735
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发表时间：
2019-11-06
影响因子：
5.2
通讯作者：
Taneera, Jalal
中科院分区：
文献类型：
--
作者：
Aljaibeji, Hayat;Mukhopadhyay, Debasmita;Taneera, Jalal
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 beta-cells associates with downregulation of the key insulin signaling and insulin biosynthesis genes as well as reduction in glucose sensing.
