PMID- 28720696 OWN - NLM STAT- MEDLINE DCOM- 20171002 LR - 20181217 IS - 1939-327X (Electronic) IS - 0012-1797 (Linking) VI - 66 IP - 10 DP - 2017 Oct TI - Low-Dose Persistent Organic Pollutants Impair Insulin Secretory Function of Pancreatic beta-Cells: Human and In Vitro Evidence. PG - 2669-2680 LID - 10.2337/db17-0188 [doi] AB - 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 approximately 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. CI - (c) 2017 by the American Diabetes Association. FAU - Lee, Yu-Mi AU - Lee YM AUID- ORCID: 0000-0003-3206-7894 AD - Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. FAU - Ha, Chae-Myeong AU - Ha CM AD - Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea. AD - BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea. FAU - Kim, Se-A AU - Kim SA AD - Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea. AD - BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea. FAU - Thoudam, Themis AU - Thoudam T AD - Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea. AD - BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea. FAU - Yoon, Young-Ran AU - Yoon YR AD - BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea. AD - Department of Biomedical Science, School of Medicine, Kyungpook National University and Hospital, Daegu, Republic of Korea. FAU - Kim, Dae-Jung AU - Kim DJ AD - Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea. FAU - Kim, Hyeon-Chang AU - Kim HC AUID- ORCID: 0000-0001-7867-1240 AD - Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - Moon, Hyo-Bang AU - Moon HB AD - Department of Environmental Marine Sciences, College of Science and Technology, Hanyang University, Ansan, Republic of Korea. FAU - Park, Sungmi AU - Park S AD - Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University, Daegu, Republic of Korea. FAU - Lee, In-Kyu AU - Lee IK AD - BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea lee_dh@knu.ac.kr leei@knu.ac.kr. AD - Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University, Daegu, Republic of Korea. AD - Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. FAU - Lee, Duk-Hee AU - Lee DH AUID- ORCID: 0000-0003-1596-9968 AD - Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea lee_dh@knu.ac.kr leei@knu.ac.kr. AD - BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea. LA - eng PT - Journal Article DEP - 20170718 PL - United States TA - Diabetes JT - Diabetes JID - 0372763 RN - 0 (Environmental Pollutants) RN - 0 (Hydrocarbons, Chlorinated) RN - 0 (Insulin) RN - DFC2HB4I0K (Polychlorinated Biphenyls) SB - IM MH - Adult MH - Animals MH - Cell Line MH - Diabetes Mellitus, Type 2/blood/*metabolism MH - Environmental Pollutants/blood/*toxicity MH - Female MH - Glucose Tolerance Test MH - Humans MH - Hydrocarbons, Chlorinated/blood/toxicity MH - Insulin/*metabolism MH - Insulin Secretion MH - Insulin-Secreting Cells/drug effects/*metabolism MH - Male MH - Middle Aged MH - Polychlorinated Biphenyls/blood/toxicity MH - Rats EDAT- 2017/07/20 06:00 MHDA- 2017/10/03 06:00 CRDT- 2017/07/20 06:00 PHST- 2017/02/13 00:00 [received] PHST- 2017/07/13 00:00 [accepted] PHST- 2017/07/20 06:00 [pubmed] PHST- 2017/10/03 06:00 [medline] PHST- 2017/07/20 06:00 [entrez] AID - db17-0188 [pii] AID - 10.2337/db17-0188 [doi] PST - ppublish SO - Diabetes. 2017 Oct;66(10):2669-2680. doi: 10.2337/db17-0188. Epub 2017 Jul 18.