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

Aljaibeji, Hayat ; Mukhopadhyay, Debasmita ; Mohammed, Abdul Khader ; Dhaiban, Sarah ; Hachim, Mahmood Y. ; Elemam, Noha M. ; Sulaiman, Nabil ; Salehi, Albert LU orcid and Taneera, Jalal LU (2019) In Frontiers in Endocrinology 10.
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 (HbA1c). Expression silencing of PLCXD3 in INS-1 (832/13) cells was found to reduce... (More)

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 (HbA1c). 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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
gene expression, microarray, PLCXD3, RNA sequencing, type 2 diabetes
in
Frontiers in Endocrinology
volume
10
article number
735
publisher
Frontiers Media S. A.
external identifiers
  • pmid:31781030
  • scopus:85075547421
ISSN
1664-2392
DOI
10.3389/fendo.2019.00735
language
English
LU publication?
yes
id
519fac59-aa5e-4983-a348-fb9c95a2007f
date added to LUP
2019-12-06 08:39:51
date last changed
2024-05-29 04:40:19
@article{519fac59-aa5e-4983-a348-fb9c95a2007f,
  abstract     = {{<p>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<sub>1c</sub>). 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.</p>}},
  author       = {{Aljaibeji, Hayat and Mukhopadhyay, Debasmita and Mohammed, Abdul Khader and Dhaiban, Sarah and Hachim, Mahmood Y. and Elemam, Noha M. and Sulaiman, Nabil and Salehi, Albert and Taneera, Jalal}},
  issn         = {{1664-2392}},
  keywords     = {{gene expression; microarray; PLCXD3; RNA sequencing; type 2 diabetes}},
  language     = {{eng}},
  month        = {{11}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Endocrinology}},
  title        = {{Reduced Expression of PLCXD3 Associates With Disruption of Glucose Sensing and Insulin Signaling in Pancreatic β-Cells}},
  url          = {{http://dx.doi.org/10.3389/fendo.2019.00735}},
  doi          = {{10.3389/fendo.2019.00735}},
  volume       = {{10}},
  year         = {{2019}},
}