In vitro effect of DDE exposure on the regulation of B-TC-6 pancreatic beta cell insulin secretion: a potential role in beta cell dysfunction and type 2 diabetes mellitus

Abstract

Organochlorine compounds (OC) include synthetic insecticides previously used throughout the world before being banned for their adverse effects and environmental persistence; DDT (dichlorodiphenyltrichloroethane) was one of the most widely used. Epidemiological evidence suggests that higher levels of some OC, including metabolites of DDT, such as dichlorodiphenyldichloroethylene (DDE), are associated with type 2 diabetes mellitus (T2D). DDE exposure may affect pancreatic cellular functions associated with glucose control and possibly cause beta cell dysfunction. The in vitro effect of DDE exposure on pancreatic beta cell insulin secretion was investigated using Beta-Tumor Cell-6 (B-TC-6) murine pancreatic beta cells. DDE exposure significantly increased insulin secretion suggesting a role for DDE in altering insulin synthesis and secretion. Reactive oxygen species (ROS) levels were not significantly increased indicating that oxidative stress is not responsible for the DDE-induced insulin secretion. Pancreatic and duodenal homeobox factor-1 (PDX-1) levels were not significantly increased suggesting that DDE exposure does not alter insulin transcription, but prohormone convertase (PC) levels were increased suggesting a role for DDE in altering insulin translation. Based on these in vitro results, DDE may play a role in beta cell dysfunction by affecting mechanisms that regulate insulin secretion but it is not likely to be the major mechanism behind the DDE/T2D epidemiological association.

Keywords:

• Organochlorines
• diabetes
• pancreas
• insulin
• prohormone convertase

Acknowledgments

Dr. Lauren Mangum and Dr. Edward Meek are acknowledged for technical assistance and Dr. Robert Wills for the statistical analysis.

Disclosure statement

The authors report no conflict of interest.

Data availability statement

The data that support the findings of this study are available from the corresponding author, JEC, upon reasonable request.

Additional information

Funding

This research was supported by the Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA