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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.

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