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 b-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 b-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 (Ptrend = 0.02). Dynamic first-phase insulin secretion remarkably decreased with increasing concentrations of OCPs among only insulin-sensitive individuals (Ptrend = 0.02); the insulin levels among individuals with high OCPs were ?30% of those with low OCPs. Compared with OCPs, PCBs showed weaker associations. The decreased insulin secretion by INS-1E b-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 b-cell dysfunction.
Bibliographical noteFunding Information:
Funding. 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). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. Y.-M.L. performed the statistical analyses and drafted the human data parts of the manuscript. C.-M.H. and S.P. performed the in vitro experiments and drafted the in vitro data parts of the manuscript. S.-A.K. conducted the experiments on human subjects. T.T. performed the in vitro experiments. Y.-R.Y., D.-J.K., H.-C.K., and H.-B.M. contributed to the discussion. I.-K.L. conceived the hypothesis and edited the manuscript. D.-H.L. conceived the hypothesis, led the project, and edited the manuscript. D.-H.L. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
All Science Journal Classification (ASJC) codes
- Internal Medicine
- Endocrinology, Diabetes and Metabolism