Background & objective: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that is characterized by an early onset, autosomal dominant mode of inheritance and a primary defect in pancreatic β-cell function. MODY has been identified in Asian populations, however, there is a big discrepancy in the genetic locus between Asian and Caucasian patients with MODY. We previously reported that mutations in PTPRD, SYT9 and WFS1 have been identified in Korean families of MODY patients(Horm Res Pediatr, 2015). In this study, we investigated whether mutations (mut) of PTPRD, SYT9 and WFS1 overexpression vectors effected insulin release in human pancreatic beta cell.
Materials & Methods: We used 1.2B4 and 1.4E7 β cell lines for human pancreatic β cells. PTPRD, mut-PTPRD (c.620C>T:p. Thr 207 Ile), SYT9, mut-SYT9 (c.559C>G:p.Gln187Glu), WFS1 and mut-WFS1 (c.1526T>G:p.Val 509 Gly) overexpression vectors were manufactured and transfected into 1.2B4 and 1.4E7 β cells, then confirm insulin release.
Results: Glucose induced insulin release in 1.2B4 and 1.4E7 β cells. There was no change in insulin release by glucose in 1.2B4 and 1.4E7 β cells transfected with PTPRD, SYT9 and WFS1 overexpression vectors. Interestingly, the deficit of increased insulin release was 1012% for mut-WFS1 and 3035% for mut-SYT9 and mut-PTPRD, respectively in 1.2B4 and 1.4E7 β cells.
Conclusions: Based on the literatures and our findings, SYT9 and PTPRD are promising candidate genes with the potential of MODY family. In addition, further evaluation of cell signals related to insulin secretion by these genes is needed in the future.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology