Copine 3 “CPNE3” is a novel regulator for insulin secretion and glucose uptake in pancreatic β-cells

Copine 3 (CPNE3) is a calcium-dependent phospholipid-binding protein that has been found to play an essential role in cancer progression and stages. However, its role in pancreatic β-cell function has not been investigated. Therefore, we performed a serial of bioinformatics and functional experiments to explore the potential role of Cpne3 on insulin secretion and β-cell function in human islets and INS-1 (832/13) cells. RNA sequencing and microarray data revealed that CPNE3 is highly expressed in human islets compared to other CPNE genes. In addition, expression of CPNE3 was inversely correlated with HbA1c and reduced in human islets from hyperglycemic donors. Silencing of Cpne3 in INS-1 cells impaired glucose-stimulated insulin secretion (GSIS), insulin content and glucose uptake efficiency without affecting cell viability or inducing apoptosis. Moreover, mRNA and protein expression of the key regulators in glucose sensing and insulin secretion (Insulin, GLUT2, NeuroD1, and INSR) were downregulated in Cpne3-silenced cells. Taken together, data from the present study provides a new understanding of the role of CPNE3 in maintaining normal β-cell function, which might contribute to developing a novel target for future management of type 2 diabetes therapy.