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

Diabetes. 2017 Oct;66(10):2669-2680. doi: 10.2337/db17-0188. Epub 2017 Jul 18.

Abstract

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 β-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 β-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 β-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 β-cell dysfunction.

MeSH terms

  • Adult
  • Animals
  • Cell Line
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism*
  • Environmental Pollutants / blood
  • Environmental Pollutants / toxicity*
  • Female
  • Glucose Tolerance Test
  • Humans
  • Hydrocarbons, Chlorinated / blood
  • Hydrocarbons, Chlorinated / toxicity
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Male
  • Middle Aged
  • Polychlorinated Biphenyls / blood
  • Polychlorinated Biphenyls / toxicity
  • Rats

Substances

  • Environmental Pollutants
  • Hydrocarbons, Chlorinated
  • Insulin
  • Polychlorinated Biphenyls