Persistent organic pollutant concentrations in human pancreas correlate with markers of beta cell dysfunction.

Abstract

Epidemiological studies consistently report associations between circulating concentrations of persistent organic pollutants and increased type 2 diabetes risk. Measures of pollutant concentrations in pancreas are limited; given the role of the endocrine pancreas in diabetes pathogenesis, this is an important gap in the literature. Additionally, no studies have correlated pollutant concentrations with direct measures of human beta cell function. We measure concentrations from 3 pollutant classes-dioxins/furans, polychlorinated biphenyls, and organochlorine pesticides-in pancreas and peripancreatic adipose tissue biopsies obtained from 31 human organ donors. We show that pollutants are consistently detected in human pancreas, and for some analytes, at higher concentrations than in adipose. We next assess correlations between pollutant concentrations and systemic indicators of diabetes risk (body mass index, age, and haemoglobin A1c) and direct measures of beta cell function in isolated islets from the same 31 donors. Pancreas polychlorinated biphenyls and organochlorine pesticides positively correlate with body mass index, age and basal insulin secretion but negatively correlate with stimulation index (ratio of insulin secretion under high glucose / low glucose conditions). Pancreas dioxins/furans positively correlate with fatty acid- and amino acid-stimulated insulin secretion. These data indicate that lipophilic pollutants accumulate in human pancreas and positively correlate with surrogate markers of diabetes risk.