Reduced Expression of PLCXD3 Associates With Disruption of Glucose Sensing and Insulin Signaling in Pancreatic β-Cells
| Autor: | Sarah Dhaiban, Nabil Sulaiman, Jalal Taneera, Albert Salehi, Debasmita Mukhopadhyay, Noha Mousaad Elemam, Mahmood Y. Hachim, Abdul Khader Mohammed, Hayat Aljaibeji |
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| Rok vydání: | 2019 |
| Předmět: |
PLCXD3
0301 basic medicine medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment 030209 endocrinology & metabolism Type 2 diabetes lcsh:Diseases of the endocrine glands. Clinical endocrinology 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Internal medicine Gene expression medicine Protein kinase B lcsh:RC648-665 biology Chemistry Insulin RNA sequencing medicine.disease IRS2 Insulin receptor 030104 developmental biology Endocrinology gene expression biology.protein GLUT2 type 2 diabetes microarray |
| Zdroj: | Frontiers in Endocrinology, Vol 10 (2019) |
| ISSN: | 1664-2392 |
| DOI: | 10.3389/fendo.2019.00735 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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