Mitochondrial Dysfunction and Insulin Resistance: The Contribution of Dioxin-Like Substances

Abstract

Persistent organic pollutants (POPs) are known to cause mitochondrial dysfunction and this in turn is linked to insulin resistance, a key biochemical abnormality underlying the metabolic syndrome. To establish the cause and effect relationship between exposure to POPs and the development of the metabolic syndrome, Koch's postulates were considered. Problems arising from this approach were discussed and possible solutions were suggested. In particular, the difficulty of establishing a cause and effect relationship due to the vagueness of the metabolic syndrome as a disease entity was discussed. Recently a bioassay, aryl-hydrocarbon receptor (AhR) trans-activation activity using a cell line expressing AhR-luciferase, showed that its activity is linearly related with the parameters of the metabolic syndrome in a population. This finding suggests the possible role of bioassays in the analysis of multiple pollutants of similar kinds in the pathogenesis of several closely related diseases, such as type 2 diabetes and the metabolic syndrome. Understanding the effects of POPs on mitochondrial function will be very useful in understanding the integration of various factors involved in this process, such as genes, fetal malnutrition and environmental toxins and their protectors, as mitochondria act as a unit according to the metabolic scaling law.

Potential contribution of insecticide exposure and development of obesity and type 2 diabetes

“…Studies have demonstrated that pancreatic beta cell failure induced by insecticide exposure could be the result of underlying mitochondrial dysfunction in the pancreas (Lee, 2011; Lim et al, 2009; Mostafalou and Abdollahi, 2013). It is reported that the pancreas is more susceptible to reactive oxygen species than other tissues because of its relative low expression of defensive enzymes against reactive oxygen species (Grankvist et al, 1981; Ho and Bray, 1999; Kakkar et al, 1998).…”

Persistent organic pollutants and biomarkers of diabetes risk in a cohort of Great Lakes sport caught fish consumers

“…Possible biologic pathways through which POPs could affect diabetes incidence have been hypothesized, including insulin resistance (Kern et al 2004), pancreatic beta cell destruction (De Tata 2014), mitochondrial dysfunction (Lee 2011), alterations in steroid metabolism (Persky et al 2011;Persky et al 2012), antagonism of PPARγ expression (Remillard and Bunce 2002), and induction of low grade chronic inflammation (Fujiyoshi et al 2006), oxidative stress (Lee et al 2008), and autoimmunity (Langer et al 2002). This study explored some of these potential pathways using biomarkers of diabetes risk.…”

Increased Susceptibility to Metabolic Syndrome in Adult Offspring of Angiotensin Type 1 Receptor Autoantibody-Positive Rats

“…Second, on reaching 40 weeks old (equivalent to human middle-aged life), having been fed a normal diet, AT1-Ab-positive pregnant rats' offspring exhibited normal FPG and blood pressure, but elevated serum insulin levels and increased HOMA-IR, indicating IR, while the vehicle group's metabolic parameters remained normal. Moreover, IR is a precursor to MetS, which may be due to genetic changes and/or adverse environmental factors (13,18). The present study's data suggest that offspring born to AT1-Ab-positive mothers may have increased susceptibility to metabolic derangement by middle age.…”