Impact of chronic and low cadmium exposure of rats: sex specific disruption of glucose metabolism

Abstract

BackgroundSeveral epidemiological and animal studies suggest a positive association between cadmium (Cd) exposure and incidence of type 2 diabetes, but the association remains controversial. Besides, the experimental data have mainly been obtained with relatively high levels of Cd, over various periods of time, and with artificial routes of administration. ObjectivesDo environmental exposures to Cd induce significant disruption of glucose metabolism? MethodsAdults Wistar rats were exposed for three months to 0, 5, 50 or 500 μg.kg−1.d−1 of CdCl2 in drinking water. Relevant parameters of glucose homeostasis were measured. ResultsCd accumulated in plasma, kidney and liver of rats exposed to 50 and 500 μg.kg−1.d−1, without inducing signs of organ failure. In rats drinking 5 μg.kg−1.d−1 for 3 months, Cd exposure did not lead to any significant increase of Cd in these organs. At 50 and 500 μg.kg−1.d−1 of Cd, glucose and insulin tolerance were unchanged in both sexes. However, females exhibited a significant increase of both fasting and glucose-stimulated plasma insulin that was assigned to impaired hepatic insulin extraction as indicated by unaltered fasting C-peptide plasma levels. ConclusionsGlucose homeostasis is sensitive to chronic Cd exposure in a gender-specific way. Moreover, this study proves that an environmental pollutant such as Cd can have, at low concentrations, an impact on the glucose homeostatic system and it highlights the importance of a closer scrutiny of the underlying environmental causes to understand the increased incidence of type 2 diabetes.