title: Exposure to p,p'-dichlorodiphenyldichloroethylene (DDE) induces fasting hyperglycemia without insulin resistance in male C57BL/6H mice.
abstract: 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.
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, Mississippi State University College of Veterinary Medicine, Mississippi State, MS 39762, United States. Electronic address: thowell@cvm.msstate.edu.
authors.forename: George E
authors.initials: GE
authors.lastname: Howell
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, Mississippi State University College of Veterinary Medicine, Mississippi State, MS 39762, United States.
authors.forename: Edward
authors.initials: E
authors.lastname: Meek
authors.affiliation: Department of Biological Sciences, Mississippi College, Clinton, MS 39058, United States.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kilic
authors.affiliation: Department of Biological Sciences, Mississippi College, Clinton, MS 39058, United States.
authors.forename: Mariel
authors.initials: M
authors.lastname: Mohns
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, Mississippi State University College of Veterinary Medicine, Mississippi State, MS 39762, United States; Department of Biological Sciences, Mississippi College, Clinton, MS 39058, United States.
authors.forename: Charlee
authors.initials: C
authors.lastname: Mulligan
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, Mississippi State University College of Veterinary Medicine, Mississippi State, MS 39762, United States.
authors.forename: Janice E
authors.initials: JE
authors.lastname: Chambers
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003633:Dichlorodiphenyl Dichloroethylene / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005215:Fasting; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000139:chemically induced*; D007328:Insulin / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010575:Pesticides / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D004785:Environmental Pollutants; D007328:Insulin; D010575:Pesticides; D003633:Dichlorodiphenyl Dichloroethylene; D051057:Proto-Oncogene Proteins c-akt
keywords: C57BL/6 mice; DDE; Diabetes; Glucose; Organochlorine compounds; Persistent organic pollutants