Characterizing the Effects of Dechlorane Plus on β-cells: a Comparative Study Across Models and Species

Overview

Journal Islets

Specialties Endocrinology
Gastroenterology

Date 2024 Jun 4

PMID 38833523

Authors

Kyle A van Allen

Noa Gang

Myriam P Hoyeck

Ineli Perera

Dahai Zhang

Ella Atlas

Francis C Lynn

Jennifer E Bruin

Affiliations

Soon will be listed here.

Abstract

Epidemiological studies consistently link environmental toxicant exposure with increased Type 2 diabetes risk. Our study investigated the diabetogenic effects of a widely used flame retardant, Dechlorane Plus (DP), on pancreatic β-cells using rodent and human model systems. We first examined pancreas tissues from male mice exposed daily to oral gavage of either vehicle (corn oil) or DP (10, 100, or 1000 μg/kg per day) and fed chow or high fat diet for 28-days . DP exposure did not affect islet size or endocrine cell composition in either diet group. Next, we assessed the effect of 48-hour exposure to vehicle (DMSO) or DP (1, 10, or 100 nM) using immortalized rat β-cells (INS-1 832/3), primary mouse and human islets, and human stem-cell derived islet-like cells (SC-islets). In INS-1 832/3 cells, DP did not impact glucose-stimulated insulin secretion (GSIS) but significantly decreased intracellular insulin content. DP had no effect on GSIS in mouse islets or SC-islets but had variable effects on GSIS in human islets depending on the donor. DP alone did not affect insulin content in mouse islets, human islets, or SC-islets, but mouse islets co-exposed to DP and glucolipotoxic (GLT) stress conditions (28.7 mM glucose + 0.5 mM palmitate) had reduced insulin content compared to control conditions. Co-exposure of mouse islets to DP + GLT amplified the upregulation of compared to GLT alone. Our study highlights the importance and challenges of using different models for studying chemical toxicity.

References

Wang Y, Danielson K, Ropski A, Harvat T, Barbaro B, Paushter D . Systematic analysis of donor and isolation factor's impact on human islet yield and size distribution. Cell Transplant. 2013; 22(12):2323-33. PMC: 3923650. DOI: 10.3727/096368912X662417. View

Mehran A, Templeman N, Brigidi G, Lim G, Chu K, Hu X . Hyperinsulinemia drives diet-induced obesity independently of brain insulin production. Cell Metab. 2012; 16(6):723-37. DOI: 10.1016/j.cmet.2012.10.019. View

Gregg B, Moore P, Demozay D, Hall B, Li M, Husain A . Formation of a human β-cell population within pancreatic islets is set early in life. J Clin Endocrinol Metab. 2012; 97(9):3197-206. PMC: 3431572. DOI: 10.1210/jc.2012-1206. View

Wang S, Tsai P, Yang C, Guo Y . Increased risk of diabetes and polychlorinated biphenyls and dioxins: a 24-year follow-up study of the Yucheng cohort. Diabetes Care. 2008; 31(8):1574-9. PMC: 2494618. DOI: 10.2337/dc07-2449. View

Zhang Z, Sun Z, Xiao X, Zhou S, Wang X, Gu J . Mechanism of BDE209-induced impaired glucose homeostasis based on gene microarray analysis of adult rat liver. Arch Toxicol. 2013; 87(8):1557-67. DOI: 10.1007/s00204-013-1059-8. View

Yanagisawa R, Koike E, Win-Shwe T, Yamamoto M, Takano H . Impaired lipid and glucose homeostasis in hexabromocyclododecane-exposed mice fed a high-fat diet. Environ Health Perspect. 2014; 122(3):277-83. PMC: 3948039. DOI: 10.1289/ehp.1307421. View

Karandrea S, Yin H, Liang X, Heart E . BDE-47 and BDE-85 stimulate insulin secretion in INS-1 832/13 pancreatic β-cells through the thyroid receptor and Akt. Environ Toxicol Pharmacol. 2017; 56:29-34. DOI: 10.1016/j.etap.2017.08.030. View

Templeman N, Skovso S, Page M, Lim G, Johnson J . A causal role for hyperinsulinemia in obesity. J Endocrinol. 2017; 232(3):R173-R183. DOI: 10.1530/JOE-16-0449. View

Peshdary V, Styles G, Rigden M, Caldwell D, Kawata A, Sorisky A . Exposure to Low Doses of Dechlorane Plus Promotes Adipose Tissue Dysfunction and Glucose Intolerance in Male Mice. Endocrinology. 2020; 161(8). DOI: 10.1210/endocr/bqaa096. View

10.

Hogrebe N, Maxwell K, Augsornworawat P, Millman J . Generation of insulin-producing pancreatic β cells from multiple human stem cell lines. Nat Protoc. 2021; 16(9):4109-4143. PMC: 8529911. DOI: 10.1038/s41596-021-00560-y. View

11.

Ibrahim M, MacFarlane E, Matteo G, Hoyeck M, Rick K, Farokhi S . Functional cytochrome P450 1A enzymes are induced in mouse and human islets following pollutant exposure. Diabetologia. 2019; 63(1):162-178. PMC: 6890627. DOI: 10.1007/s00125-019-05035-0. View

12.

Ben Y, Li X, Yang Y, Li L, Di J, Wang W . Dechlorane Plus and its dechlorinated analogs from an e-waste recycling center in maternal serum and breast milk of women in Wenling, China. Environ Pollut. 2012; 173:176-81. DOI: 10.1016/j.envpol.2012.09.028. View

13.

Novakovsky G, Sasaki S, Fornes O, Omur M, Huang H, Bayly C . In silico discovery of small molecules for efficient stem cell differentiation into definitive endoderm. Stem Cell Reports. 2023; 18(3):765-781. PMC: 10031281. DOI: 10.1016/j.stemcr.2023.01.008. View

14.

Klemen M, Dolensek J, Rupnik M, Stozer A . The triggering pathway to insulin secretion: Functional similarities and differences between the human and the mouse β cells and their translational relevance. Islets. 2017; 9(6):109-139. PMC: 5710702. DOI: 10.1080/19382014.2017.1342022. View

15.

Linnemann A, Baan M, Davis D . Pancreatic β-cell proliferation in obesity. Adv Nutr. 2014; 5(3):278-88. PMC: 4013180. DOI: 10.3945/an.113.005488. View

16.

Ongono J, Dow C, Gambaretti J, Severi G, Boutron-Ruault M, Bonnet F . Dietary exposure to brominated flame retardants and risk of type 2 diabetes in the French E3N cohort. Environ Int. 2018; 123:54-60. DOI: 10.1016/j.envint.2018.11.040. View

17.

Mitchell R, Hu M, Chabosseau P, Cane M, Meur G, Bellomo E . Molecular Genetic Regulation of Slc30a8/ZnT8 Reveals a Positive Association With Glucose Tolerance. Mol Endocrinol. 2015; 30(1):77-91. PMC: 4995240. DOI: 10.1210/me.2015-1227. View

18.

Brissova M, Niland J, Cravens J, Olack B, Sowinski J, Evans-Molina C . The Integrated Islet Distribution Program answers the call for improved human islet phenotyping and reporting of human islet characteristics in research articles. Diabetologia. 2019; 62(7):1312-1314. PMC: 7365209. DOI: 10.1007/s00125-019-4876-3. View

19.

Hohmeier H, Mulder H, Chen G, Prentki M, Newgard C . Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion. Diabetes. 2000; 49(3):424-30. DOI: 10.2337/diabetes.49.3.424. View

20.

Lyon J, Manning Fox J, Spigelman A, Kim R, Smith N, OGorman D . Research-Focused Isolation of Human Islets From Donors With and Without Diabetes at the Alberta Diabetes Institute IsletCore. Endocrinology. 2015; 157(2):560-9. DOI: 10.1210/en.2015-1562. View