Abstract

Epidemiological studies consistently report associations between circulating concentrations of persistent organic pollutants (POPs) and increased type 2 diabetes risk. Measures of POP 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 POP concentrations with direct measures of beta cell function in humans. We hypothesized that lipophilic POPs accumulate in human pancreas and correlate with markers of diabetes risk. To test this hypothesis, we measured POP concentration from 3 chemical classes – dioxins/furans, polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) – in pancreas and peripancreatic adipose tissue biopsies obtained from 31 human organ donors via the Alberta Diabetes Institute IsletCore. Indeed, POPs were consistently detected in human pancreas, and for some pollutants, at higher concentrations than in adipose. We next assessed correlations between POP concentrations and systemic indicators of diabetes risk (BMI, age, and %HbA1c) and direct measures of beta cell function. To this end, we measured insulin secretion in response to numerous secretagogues (i.e. glucose, fatty acids, amino acids, exendin-4, or KCl) in isolated islets from the same 31 donors. Pancreas PCBs and OCPs positively correlated with BMI, age and basal insulin secretion but negatively correlated with stimulation index (ratio of insulin secretion under high glucose / low glucose conditions). In contrast, pancreas dioxins/furans positively correlated with fatty acid- and amino acid-stimulated insulin secretion. These data confirm that lipophilic pollutants accumulate in human pancreas and positively correlate with markers of diabetes risk.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This research was supported by a Canadian Institutes of Health Research (CIHR) Project Grant (#PJT-2018-159590). J.E.B. is supported by an Early Researcher Award from the Ontario Government. E.E.M is supported by a Diabetes Canada End Diabetes Award (OG-3-24-5818-EM). M.P.H. was supported by a CIHR CGS-D award. M.E.A.C. was supported by an NSERC CGS-M and NSERC CGS-D award. J.P. was supported by the Guiding interdisciplinary Research on Womens and girls health and Wellbeing (GROWW) scholarship and Ontario Graduate Scholarship. This work includes data from HumanIslets.com funded by the Canadian Institutes of Health Research, JDRF Canada, and Diabetes Canada (5-SRA-2021-1149-S-B/TG 179092) with data from islets isolated by the Alberta Diabetes Institute IsletCore with the support of the Human Organ Procurement and Exchange program, Trillium Gift of Life Network, BC Transplant, Quebec Transplant, and other Canadian organ procurement organizations.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

the Research Ethics Board at Carleton University (#106701) and the University of Alberta (Pro00013094) gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors.

AbbreviationsAhRAryl hydrocarbon receptorCYP1A1Cytochrome P450 1A1DLDioxin-likeNDLNon-dioxin-likeOCPsOrganochlorine pesticidesPCBsPolychlorinated biphenylsPCDDsPolychlorodibenzo-p-dioxinsPCDFsPolychlorodibenzofuransPOPsPersistent organic pollutantsT2DType 2 diabetesTCDD2,3,7,8-tetrachlorodibenzo-p-dioxin