PMID- 24582731 OWN - NLM STAT- MEDLINE DCOM- 20140623 LR - 20220318 IS - 1879-3185 (Electronic) IS - 0300-483X (Print) IS - 0300-483X (Linking) VI - 320 DP - 2014 Jun 5 TI - Exposure to p,p'-dichlorodiphenyldichloroethylene (DDE) induces fasting hyperglycemia without insulin resistance in male C57BL/6H mice. PG - 6-14 LID - S0300-483X(14)00029-8 [pii] LID - 10.1016/j.tox.2014.02.004 [doi] AB - 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. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Howell, George E 3rd AU - Howell GE 3rd AD - 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. FAU - Meek, Edward AU - Meek E AD - Center for Environmental Health Sciences, Department of Basic Sciences, Mississippi State University College of Veterinary Medicine, Mississippi State, MS 39762, United States. FAU - Kilic, Jessica AU - Kilic J AD - Department of Biological Sciences, Mississippi College, Clinton, MS 39058, United States. FAU - Mohns, Mariel AU - Mohns M AD - Department of Biological Sciences, Mississippi College, Clinton, MS 39058, United States. FAU - Mulligan, Charlee AU - Mulligan C AD - 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. FAU - Chambers, Janice E AU - Chambers JE AD - Center for Environmental Health Sciences, Department of Basic Sciences, Mississippi State University College of Veterinary Medicine, Mississippi State, MS 39762, United States. LA - eng GR - R15 ES019742/ES/NIEHS NIH HHS/United States GR - R15ES019742/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140226 PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - 0 (Blood Glucose) RN - 0 (Environmental Pollutants) RN - 0 (Insulin) RN - 0 (Pesticides) RN - 4M7FS82U08 (Dichlorodiphenyl Dichloroethylene) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/drug effects/metabolism MH - Animals MH - Blood Glucose/drug effects MH - Dichlorodiphenyl Dichloroethylene/administration & dosage/*toxicity MH - Dose-Response Relationship, Drug MH - Environmental Exposure/*adverse effects MH - Environmental Pollutants/administration & dosage/*toxicity MH - Fasting MH - Glucose Tolerance Test MH - Hyperglycemia/*chemically induced MH - Insulin/physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Pesticides/*toxicity MH - Phosphorylation/drug effects MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Time Factors PMC - PMC4098932 MID - NIHMS571186 OTO - NOTNLM OT - C57BL/6 mice OT - DDE OT - Diabetes OT - Glucose OT - Organochlorine compounds OT - Persistent organic pollutants COIS- 7. Conflict of interest statement: There are no conflicts of interest by any authors. EDAT- 2014/03/04 06:00 MHDA- 2014/06/24 06:00 PMCR- 2015/06/05 CRDT- 2014/03/04 06:00 PHST- 2013/11/19 00:00 [received] PHST- 2014/01/30 00:00 [revised] PHST- 2014/02/10 00:00 [accepted] PHST- 2014/03/04 06:00 [entrez] PHST- 2014/03/04 06:00 [pubmed] PHST- 2014/06/24 06:00 [medline] PHST- 2015/06/05 00:00 [pmc-release] AID - S0300-483X(14)00029-8 [pii] AID - 10.1016/j.tox.2014.02.004 [doi] PST - ppublish SO - Toxicology. 2014 Jun 5;320:6-14. doi: 10.1016/j.tox.2014.02.004. Epub 2014 Feb 26.