Sorting nexin 19 regulates the number of dense core vesicles in pancreatic β-cells

Aims/Introduction: Insulinoma-associated protein 2 (IA-2) regulates insulin secretion and the number of dense core vesicles (DCV). However, the mechanism of regulation of DCV number by IA-2 is unknown. We examined the effect of sorting nexin 19 (SNX19), an IA-2 interacting protein, on insulin secretion and the number of dense core vesicles (DCV). Materials and Methods: Stable SNX19 knockdown (SNX19KD) MIN6, a mouse pancreatic β-cell line, and stable SNX19-reintroduced SNX19KD MIN6 were established. Quantification of DCV, and lysosomes was carried out using electron micrographs. The half-life of DCV was detected by pulse-chase experiment. Results: Insulin secretion and content were decreased in stable SNX19KD MIN6 cells compared with those in control MIN6 cells. Electron micrographs showed that DCV number in SNX19KD cells was decreased by approximately 75% and that DCV size was decreased by approximately 40% compared with those in control cells, respectively. Furthermore, when SNX19 was reintroduced in SNX19KD cells, insulin content, insulin secretion and DCV number were increased. The half-life of DCV was decreased in SNX19KD cells, but was increased in SNX19KD cells in which SNX19 was reintroduced. The number of lysosomes and the activity of lysosome enzyme cathepsin D were increased by approximately threefold in SNX19KD cells compared with those in control cells. In contrast, they were decreased to approximately half to one-third in SNX19-reintroduced SNX19KD cells. Conclusions: SNX19 regulates the number of DCV and insulin content by stabilizing DCV in β-cells. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00138.x, 2012)