Linking dioxins to diabetes: epidemiology and biologic plausibility.
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.
Toxicology Program, University of Guelph, Guelph, Ontario, Canada.
Rene B J
RB
Remillard
Nigel J
NJ
Bunce
D000328:Adult; D017668:Age of Onset; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000209:etiology* / Q000503:physiopathology; D004147:Dioxins / Q000009:adverse effects*; D004781:Environmental Exposure; D016021:Epidemiologic Studies; D006801:Humans; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000187:drug effects / Q000502:physiology*
D004147:Dioxins; D018336:Receptors, Aryl Hydrocarbon; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors