| Linking Dioxins to Diabetes: Epidemiology and Biologic Plausibility Rene B. J. Remillard and Nigel J. Bunce Toxicology Program, University of Guelph, Guelph, Ontario, Canada Abstract
Recent epidemiologic studies suggest a possible association between dioxin-like compounds (DLCs) and diabetes in human populations, although experimental links between DLCs and diabetes are lacking. The public health significance of such an association is that all populations are exposed to small but measurable levels of DLCs, chronic low-dose exposure to which may hasten the onset of adult-onset diabetes in susceptible individuals. In this article, we review the epidemiologic studies and propose biologically plausible connections between dioxins and diabetes. Specifically, we suggest that aryl hydrocarbon (Ah) receptor functions may antagonize peroxisome proliferator-activated receptor (PPAR) functions, and hence that the Ah receptor may promote diabetogenesis through a mechanism of PPAR antagonism. Key words: Ah receptor, diabetes, non-insulin-dependent diabetes mellitus, peroxisome proliferator-activated receptors, PPAR , 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, type 2 diabetes. Environ Health Perspect 110:853-858 (2002) . [Online 17 July 2002] http://ehpnet1.niehs.nih.gov/docs/2002/110p853-858remillard/ abstract.html Address correspondence to N.J. Bunce, Department of Chemistry and Biochemistry, Guelph, Ontario, Canada N1G 2W1. Telephone: (519) 824-4120 ext. 3962. Fax: (519) 766-1499. E-mail: bunce@chembio.uoguelph.ca We thank A. Meek for his comments on a draft of the manuscript. We gratefully acknowledge financial support provided by the Natural Sciences and Engineering Research Council of Canada. Received 6 June 2001 ; accepted 14 December 2001.
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