Approximately 8.3% of the United States (U.S.) population have either diagnosed or undiagnosed
diabetes mellitus. Out of all the cases of
diabetes mellitus, approximately 90-95% of these cases are
type 2 diabetes mellitus (T2D). Although the exact cause of T2D remains elusive, predisposing factors include age, weight, poor diet, and a sedentary lifestyle. Until recently the association between exposure to environmental contaminants and the occurrence of diabetes had been unexplored. However, recent epidemiological studies have revealed that elevated serum concentrations of certain
persistent organic pollutants (POPs), especially organochlorine pesticides, are positively associated with increased prevalence of T2D and
insulin resistance. The current study seeks to investigate if this association is causative or coincidental. Male C57BL/6H mice were exposed to
DDE (2.0mg/kg or 0.4mg/kg) or vehicle (
corn oil; 1mL/kg) for 5 days via oral gavage; fasting
blood glucose,
glucose tolerance, and
insulin challenge tests were performed following
a 7 day resting period. Exposure to
DDE caused significant
hyperglycemia compared to vehicle and this hyperglycemic effect persisted for up to 21 days following cessation of
DDE administration. Intraperitoneal
glucose tolerance tests and phosphorylation of Akt in the liver, skeletal muscle, and adipose tissue following
insulin challenge were comparable between vehicle and
DDE treated animals. To determine the direct effect of exposure to
DDE on
glucose uptake, in vitro
glucose uptake assays following
DDE exposure were performed in L6 myotubules and 3T3-L1 adipocytes. In summary, subacute exposure to
DDE does produce fasting
hyperglycemia, but this fasting
hyperglycemia does not appear to be mediated by
insulin resistance. Thus, the current study reveals that subacute exposure to
DDE does alter systemic
glucose homeostasis and may be a contributing factor to the development of
hyperglycemia associated with diabetes.