Aljaibeji Hayat, Mukhopadhyay Debasmita, Mohammed Abdul Khader, Dhaiban Sarah, Hachim Mahmood Y, Elemam Noha M, Sulaiman Nabil, Salehi Albert, Taneera Jalal
Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
Department of Clinical Sciences, Lund University Diabetes Centre (LUDC), Lund University, Malmö, Sweden.
Front Endocrinol (Lausanne). 2019 Nov 6;10:735. doi: 10.3389/fendo.2019.00735. eCollection 2019.
Previous work has shown that reduced expression of , 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 is among the highly expressed PI-PLCs in human islets and INS-1 (832/13) cells. Expression of was reduced in human diabetic islets, correlated positively with and expression and inversely with the donor's body mass index (BMI) and glycated hemoglobin (HbA). Expression silencing of in INS-1 (832/13) cells was found to reduce glucose-stimulated insulin secretion (GSIS) and insulin content. In addition, the expression of , and was downregulated. Cell viability and apoptosis rate were unaffected. In conclusion, our data suggest that low expression of in pancreatic β-cells associates with downregulation of the key insulin signaling and insulin biosynthesis genes as well as reduction in glucose sensing.
先前的研究表明,磷酸肌醇特异性磷脂酶(PI-PLC)家族成员之一的[具体名称未给出]表达降低会损害胰岛素分泌,但其机制尚不清楚。在本研究中,我们旨在利用人胰岛和大鼠INS-1(832/13)细胞来研究这种效应背后的机制。微阵列和RNA测序数据表明,[具体名称未给出]是在人胰岛和INS-1(832/13)细胞中高表达的PI-PLC之一。在人糖尿病胰岛中,[具体名称未给出]的表达降低,与[其他基因名称未给出]和[其他基因名称未给出]的表达呈正相关,与供体的体重指数(BMI)和糖化血红蛋白(HbA)呈负相关。在INS-1(832/13)细胞中沉默[具体名称未给出]的表达会降低葡萄糖刺激的胰岛素分泌(GSIS)和胰岛素含量。此外,[其他基因名称未给出]、[其他基因名称未给出]和[其他基因名称未给出]的表达下调。细胞活力和凋亡率未受影响。总之,我们的数据表明,胰腺β细胞中[具体名称未给出]的低表达与关键胰岛素信号和胰岛素生物合成基因的下调以及葡萄糖感知能力的降低有关。