Low-Dose Persistent Organic Pollutants Impair Insulin Secretory Function of Pancreatic beta-Cells: Human and In Vitro Evidence

Low-dose persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), have emerged as a new risk factor for type 2 diabetes. We evaluated whether chronic exposure to low-dose POPs affects insulin secretory function of beta-cells in humans and in vitro cells. Serum concentrations of OCPs and PCBs were measured in 200 adults without diabetes. Mathematical model-based insulin secretion indices were estimated by using a 2-h seven-sample oral glucose tolerance test. Insulin secretion by INS-1E beta-cells was measured after 48 h of treatment with three OCPs or one PCB mixture. Static second-phase insulin secretion significantly decreased with increasing serum concentrations of OCPs. Adjusted means were 63.2, 39.3, 44.1, 39.3, 39.7, and 22.3 across six categories of a summary measure of OCPs (P-trend = 0.02). Dynamic first-phase insulin secretion remarkably decreased with increasing concentrations of OCPs among only insulin-sensitive individuals (P-trend = 0.02); the insulin levels among individuals with high OCPs were approximate to 30% of those with low OCPs. Compared with OCPs, PCBs showed weaker associations. The decreased insulin secretion by INS-1E beta-cells was observed for even 1 pmol/L OCP. The data from human and in vitro cell experiments suggest that chronic exposure to low-dose POPs, especially OCPs, can induce pancreatic beta-cell dysfunction.This study was supported by the Korean Health Technology R&D Project funded by the Ministry of Health and Welfare (HI13C0715), a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare, Republic of Korea (HI16C1501), and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2017R1A2B3006406)